clinical therapeutics/new technology— glucose...

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ADA-Supported Research

CLINICAL THERAPEUTICS/NEW TECHNOLOGY—GLUCOSE MONITORING AND SENSING

CLINICAL THERAPEUTICS/NEW TECHNOLOGY— GLUCOSE MONITORING AND SENSING

2348‑PUBImpact of CME on Improving Understanding of Advances in Glucose Data InterpretationAMY LARKIN, MICHAEL LACOUTURE, ANNE LE, New York, NY

A substantial advance in the field of glucose monitoring is the develop-ment of CGM devices. We sought to determine if online continuing medical education (CME) could improve the clinical knowledge and competence of diabetologists/endocrinologists (D/Es) and nurses regarding advances in glu-cose data interpretation. A CME activity was developed as an online video discussion between 2 experts. The effects of education were assessed using a 4-question linked pre-/post-assessment study design, McNemar’s chi-squared test, and Cramer’s V for effect size.

Baseline knowledge was higher among D/E compared to nurses:∙ 63% of D/Es compared to 20% of nurses recognized similarities in

glucose monitoring devices.∙ 47% of D/Es compared to 22% of nurses recognized clinical applica-

tion of glucose data.∙ 55% of D/Es compared to 36% of nurses recognized an effective

strategy for patient engagement using glucose data.

Significant overall improvements (P < .05) were seen for both D/Es (n = 137; medium effect V= 0.171) and nurses (n = 763; small-medium effect V= 0.15).

∙ 17% more D/Es and 24% more nurses correctly recognized A1c pro-vides information about glucose exposure.

∙ 24% more D/Es and 8% more nurses correctly identified the ability to use glucose monitoring data for advancing therapy.

∙ 20% more D/Es and 17% more nurses selected an effective strategy for engaging a patient in their diabetes management plan using glu-cose data.

Additional education needed:∙ 36% of D/Es and 54% of nurses failed to recognize similarities in

glucose monitoring devices.∙ 31% of D/Es and 71% of nurses failed to recognize information pro-

vided by measuring A1c.∙ 53% of D/Es and 63% of nurses failed to recognize clinical applica-

tion of glucose data.

This study demonstrates the success of a targeted educational interven-tion on improving knowledge and competence of D/Es and nurses regarding clinical application glucose data interpretation advances. Baseline knowl-edge was higher among D/Es. Additional education on advances in glucose data is needed for both groups.

Supported By: Abbott Diabetes Care

2349‑PUBBlood Glucose Telemonitoring at Retail Pharmacies in China: The Alternative Sites for Community Diabetic CareWENHAO QU, YINGJIE LI, YING CHEN, ZHEN WANG, KAI LIU, Shanghai, China

Objective: To implement a digital solution at retail pharmacies to improve community diabetic care.

Methods: We developed a digital solution that consists of bluetooth glucose meter, an App and a cloud database for diabetic care support, and implemented the solution in 1,146 retail pharmacies in 94 cities in China. Dia-betic patients who were pharmacy members can receive in-store services of: 1) BG testing with the results synchronized to the cloud, 2) App-assisted personalized coaching, 3) App-assisted personalized meal plans, and 4) phar-macy consultation. This report profiles a diabetic population of 85,790 during Jun 6th 2015 and Nov 4th 2016.

Results: The study population had an average age of 59.7 ± 11.8, BMI of 23.7 ± 3.4, and male of 44.3%. A total of 204,887 BG tests were performed, and 28,492 people had at least 2 measurements. Both fasting blood glucose (FBG) and random blood glucoses (RBG) were improved (Figure). Plotting the baseline FBG readings against the category of each city’s economic status found a strong negative correlation r = -0.92, P = 0.029, with the lowest baseline FBG in the economically most advanced cities. Yet the same analy-sis for the glycemic control effect indicated no correlation r = -0.14, P = 0.817.

Conclusion: Regional economic status affects the population BG level and pharmacists are effective in community diabetic control regardless the geo-graphic difference.

Figure.

2350‑PUBEfficacy of PHR Integrated with EHR and Self‑Monitoring Devices on Self‑Care in Patients with Type 2 DiabetesSATOSHI TANIGUCHI, JIN TEMMA, AKIO KURODA, TORU HORIE, HIROYASU MORI, REIKO SUZUKI, YAYOI ASANO, MICHIKO ARAKI, YU TAMAKI, MUNEHIDE MATSUHISA, Tokushima, Japan

Background: Digital Personal Health Records (PHR) with tele-medicine have been proved to be effective in treating diabetes. However, simply digi-tizing logbooks (improving recording, reviewing and sharing capability) may be enough to increase adherence.

Objective: To develop and evaluate the efficacy of a PHR integrated with Electronic Health Record (EHR) and self-monitoring devices.

Method: A 3-month multi-center randomized trial was performed to type 2 diabetes patients. Intervention group used the developed PHR “e-DM Diary,” with BG monitor, digital scale, BP monitor and activity monitor. Control group used self-monitoring devices with paper logbooks issued by Japan Asso-ciation for Diabetes Education and Care, a standard protocol in Japan. The e-DM Diary or paper logbook was referenced at doctor visits. There were no other modifications to treatment.

Overview of e-DM Diary: e-DM Diary is accessed by smartphone or PC. Self-monitoring results are automatically uploaded through patient’s smartphone via Bluetooth. Patient’s EHR, including test results, treatment goals, and pre-scription information were provided automatically. Patient’s status of diabetes complications, self-monitoring goals and results, were presented in graphs.

Results: 28 participated were enrolled in this study (intervention=15/con-trol=13, age avg. 54 y.o., HbA1c 6.9%). Summary of Diabetes Self-Care Activ-ities Measure, glycemic control and body weight did not change before and after the study period in both groups, and there was no difference between groups. Patient’s age, e-Health literacy did not influence the results.

In the intervention group, 12 of 15 patients answered that e-DM Diary was effective in reducing the “hassle” of self-monitoring. There were 3 cases were the patient’s understanding of diabetes complication improved.

Conclusion: e-DM Diary’s capability to reduce hassle of self-care was recognized, and self-care supporting capability was par to paper logbooks.

Supported By: Japan Ministry of Internal Affairs and Communications

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CLINICAL THERAPEUTICS/NEW TECHNOLOGY—GLUCOSE MONITORING AND SENSING

2352‑PUBA Chinese Study to Build a HbA1c Prediction Model with 12‑Week Self‑Monitoring Blood Glucose ValuesLING WANG AN, YOU JIE ZHANG, JU MING LU, ZHAO HENG HU, YAU JIUNN LEE, LI NONG JI, A1C PREDICTION STUDY GROUP, Beijing, China, Shangluo, China, Pingtung, Taiwan

Objective: The HbA1c value is widely used to judge the diabetes control. Day-to-day diabetes management is guided by self-monitoring blood glucose (SMBG) data. To predict HbA1c with daily SMBG data may encourage people with type 2 diabetes mellitus (T2DM) to pursue good glycemic control. This retrospective study aimed to define a mathematic model to predict HbA1c value with SMBG values obtained from daily lives.

Methods: A total of 195 subjects with T2DM with 245 HbA1c and 21,375 SMBG data were analyzed. HbA1c data were collected after the 12 weeks SMBG. One HbA1c value was correspondent with a mean of 87 SMBG values.

Results: By linear regression analysis, there were significant correlation observed between the HbA1c level and past three 28-days average SMBG values (A1C=2.986+0.119×SMBG3+0.198×SMBG2+0.167×SMBG1, R2=0.432, p=0.000), allowing prediction of HbA1c with changing SMBG. The linear regression equation between the HbA1c and the 84-days SMBG values also showed good correlation (y=3.119+0.466×SMBG, R2=0.432, p=0.000). When compared the estimated HbA1c and observed HbA1c values, 70% of the sam-ples had variance within 10% and 88% of the samples had variance within 15%. Similar results were found when compared the estimated HbA1c calcu-lated by equation provide by Nathan DM (and A1c-Derived Average Glucose Study Group. Diabetes Care,2008,31:1473-1478) and the observed HbA1c values. The samples with higher variance had significantly fewer SMBG frequency (p=0.011).

Conclusions: This HbA1c prediction model could be experimentally used for subjects with T2DM in daily diabetes management. However, the vari-ance between the estimated HbA1c and real HbA1c value may be big when the SMBG frequency is low.

2353‑PUBThe Lies HbA1c TellsGABRIEL UWAIFO, JENEE NGUYEN, New Orleans, LA, Slidell, LA

HbA1c is used for diagnosis and monitoring of diabetes (DM) but there are limitations to its accuracy. We present three cases that highlight the need for caution in HbA1c use in clinical care. Case 1 is a 59 yr old African American man with > 12 yr history of type 2 DM and sickle cell disease. Past records showed normal HbA1c (4.5-5) and near normal glycoHemoglobin (5.4-7.4) despite mean blood glucose (BG) > 180mg/dl. At initial visit with us attempts to obtain HbA1c were impossible due to finding of a hemoglobin variant that influenced both ion exchange and boronate affinity HPLC. Instead, his gly-cemic profile is tracked using BG, Fructosamine and glycomark. Hemoglobin electrophoresis (HBE) showed HBSC disease. Case 2 is a 72 yr old Caucasian (C) lady referred because of discrepancies between HbA1c and BG. In the last year HbA1cs were 4.0-4.8 despite BG values in the 106-185mg/dl range. OGTT showed impaired fasting glucose. Prior HbA1cs were done using immu-noassay. At our review repeat HbA1c was sent to Mayo labs. This showed an interfering substance affecting ion-exchange HPLC. Her sample was measured using boronate affinity HPLC and HbA1c was 6.0. HBE revealed HB J- Baltimore. Case 3 is a 46 yr old C lady with morbid obesity. Her HbA1cs were in the 5.6-5.9 range and she enrolled in a lifestyle modification plan with metformin 500mg BID. After ~ 1 yr she developed intermittent bilat-eral leg paraesthesiae due to small fiber peripheral sensory neuropathy. She also had sudden onset visual blurring. Ophthalmology review showed right retinal hemorrhage with partial retinal detachment and bilateral background retinopathy consistent with diabetic retinopathy. OGTT done after holding metformin showed DM. She was commenced on liraglutide and metformin dose increased to 1000mg BID. HBE revealed a variant of HB Barts. HbA1c should be interpreted with accompanying BG measurements. When a dis-crepancy is found other indices like fructosamine and glycomark can be use-ful. Repeat HbA1cs with other methods may help identify artefactually high or low HbA1cs and so guide appropriate clinical care.

2354‑PUBMid‑infrared Quantum Cascade Laser Spectroscopy for Noninva‑sive, In Vivo Glucose SensingALEXANDRA WERTH, SABBIR LIAKAT, CLAIRE GMACHL, Princeton, NJ

Quantum cascade (QC) lasers, invented in 1994, have drastically expanded the opportunities for mid-infrared spectroscopy. The mid-infrared region, often called the fingerprint region, has strong molecular absorption features for a multitude of biomarkers. QC laser spectroscopy can provide sensitive and selective monitoring of these biomarkers. Recently, we have imple-mented a noninvasive, mobile glucose sensor based on this technology. Our system has three main components: a QC laser, an integrating sphere, and a thermal-electrically cooled mercury cadmium telluride (MCT) detector. The QC laser is swept from 8-10μm; this wavelength range contains unique spec-tral absorption features of glucose, particularly the C-O stretching mode at 9.5μm. The light penetrates into the dermis layer of the skin where it is absorbed by the glucose molecules in the interstitial fluid. The light is then backscattered off of the collagen fibers and other scatters then collected using the integrating sphere and MCT detector. Backscattered spectra are collected every 5 minutes from a single subject after eating a meal. We ana-lyze the series of collected spectra using principal component (PC) analysis to determine the wavelengths that correspond to highest variance. We con-sistently see a strong correlation with the predicted PC of the spectra and the known glucose absorption spectrum.

Figure.

Supported By: Schmidt Family Foundation; MIRTHE (EEC-0540832)

2355‑PUBContinuous Glucose Monitoring: A Training and Treatment Program for All Age GroupsULRIKE THURM, BERNHARD GEHR, MARTIN HOLDER, BERND KULZER, KARIN LANGE, ANDREAS LIEBL, CLAUDIA SAHM, SIMONE VON SENGBUSCH, THOR-STEN SIEGMUND, RALPH ZIEGLER, GUIDO FRECKMANN, SANDRA SCHLÜTER, LUTZ HEINEMANN, Ulm, Germany

Patients using a system for continuous glucose monitoring (CGM) without special training often do not achieve their intended improvement of meta-bolic control; training means translation of the information provided by the CGM system in appropriate therapeutic action and not so much handling of the system. Reimbursement for CGM is provided in Germany only if the patients are trained adequately. A team of about 20 diabetes nurses, diabe-tologists and psychologists from the German Diabetes Technology working group (AGDT) and the Pediatric Diabetology working group (AGPD) of the German Diabetes Association (DDG) has developed a structured and inde-pendent CGM training program called “SPECTRUM” (Structured patient edu-cation and treatment program for self-reliant continuous glucose monitor-ing), to ensure optimal usage of CGM. SPECTRUM consists of specific sets of slides for adults (introductory session + 6 training modules), for parents with younger children and adolescents (introductory session + 5 training modules for each version), a structured curriculum and a SPECTRUM folder. The pro-gram does not favor any given CGM system. Implementation of SPECTRUM has started in 2016; 245 diabetologists and CDEs were trained in using the adult version and 112 in the paediatric version. We have 364 health profes-sionals on the waiting list for 2017. This reflects the high needs for such a training program. Anecdotical patient reports highlight that just providing the technology is not sufficient, patients (and their treating diabetes team) need a good training to make optimal usage of this modern but expensive diagnostic option. Currently we prepare a study (CGM TRAIN) to evaluate systematically how much patients benefit from participation in such a train-ing program.

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CLINICAL THERAPEUTICS/NEW TECHNOLOGY—INSULINS

2356‑PUBImpact of Continuous Blood Glucose Monitoring on Patient Empow‑erment, Distress, and Glycemia in a High Risk PopulationARTI A. THANGUDU, DIANE BATTAGLIA, LINDA M. SIMINERIO, SANDRA I. SOBEL, Pittsburgh, PA

Background: An aim of diabetes management is to help empower patients with diabetes mellitus (DM) to interpret blood glucose monitoring (BGM) results to improve glycemia and reduce distress. Team-based care, educa-tion and continuous glucose monitoring (CGM) have been shown to improve glycemia, however, are not always available in high risk underserved com-munities.

Objective: Implement a program in a population with limited access to technology, team care and education to improve patient empowerment and glycemia while reducing distress.

Methods: Fourteen individuals with T1DM or T2DM on insulin therapy with a HbA1c >8% and/or hypoglycemia unawareness, were invited to meet with an endocrinologist who reviewed data and a diabetes educator (DE) for education on use and interpretation of CGM results. Devices were worn for seven days. The Empowerment Scale and Problem Areas in Diabetes (PAID) surveys were administered to test empowerment and diabetes-distress. HbA1c and surveys were evaluated at baseline and three months.

Results: Patient empowerment and HbA1c improved. While diabetes dis-tress worsened.

Conclusions: A comprehensive program that includes CGM, team care and education afforded improvements in glycemia to an underserved high risk population with limited access to current technology and quality care. While empowerment scores and glycemia improved, patients experienced distress. The exposure to real-time BG data and heightened diabetes aware-ness needs to be considered and further examined in a larger sample of high risk patients.

Supported By: The Beckwith Institute

2357‑PUBIs Fructosamine a Better Biomarker for Glycemic Control in Patients with Diabetes Mellitus?JANICE L. GILDEN, AMENA IQBAL, MAHWASH SIDDIQUI, SRIKAR RAPAKA, DE GAULLE DAI, ALI LADHA, BOBY G. THECKEDATH, ALVIA MOID, North Chicago, IL

Control of blood glucose has been shown to decrease diabetic complica-tions. Although, many studies have used glycosylated hemoglobin (HbA1c), an integrated value for 2-3 months of blood glucose levels, as a measure of glycemic control, several conditions, such as anemia and hemoglobin-opathies, and chronic renal failure (CKD), can result in falsely higher val-ues. Certain ethnic groups have also been observed to have higher levels of glycosylation and are not thought to have diabetes mellitus (DM). In addition, this measure does not reflect glucose variability, which may be a more important indicator, nor does it reflect recent changes in glycemic control, leading many providers to increase medications to achieve a lower value too rapidly in order to meet quality indicators, at the expense of creat-ing hypoglycemia. Unlike HbA1c, which measures the glycosylation of the hemoglobin A1 fraction with a life-span of 120 days, fructosamine measures glycosylated plasma proteins, and thus reflects glycemic control over the past 2-3 wks. In addition, fructosamine is not subject to variation by these same conditions. Therefore, we compared fructosamine to HbA1c in 140 DM patients [(age range=24-85 yrs.) (9 type 1: 131 type 2) (17 female: 123 male) (2% anemia/hemoglobinopathies: 31% CKD: 45% recent changes in medical management)]. Results demonstrated that there was a significant discordance between the expected HbA1c based upon the fructosamine [(0.017 X fructosamine + 1.61)], as well as a significant difference between the expected fructosamine based upon the HbA1c [(HbA1c-1.16) X 58.82] for the entire cohort (p<0.001). In addition, there was a negative correlation between the stage of CKD and the difference between actual and predicted HbA1c (p<0.001).

In conclusion, fructosamine may be used as another biomarker for assess-ing the current level of glycemic control in patients with DM, especially when recent changes in management have been made, as well as when other common co-morbid conditions exist.

Supported By: Captain James A. Lovell Federal Health Care Center


2358‑PUBProfiles of Patients with Type 2 Diabetes Needing 1 to 3 Injections of Insulin Lispro Mix25 in PARADIGM StudyKEITH BOWERING, DACHUANG CAO, JOÃO FELICIO, LINONG JI, HENRY SCHMITT, INDRANIL BHATTACHARYA, ABDUL JABBAR, Edmonton, AB, Canada, Indianapolis, IN, Belém, Brazil, Beijing, China, Brussels, Belgium, Gurgaon, India, Dubai, United Arab Emirates

Background: Few countries show interest in using simplified insulin mix-ture regimen with progressive intensification to decrease clinical inertia in patients on oral antidiabetic drugs (OADs).

Methods: PARADIGM was a 48-week study in patients inadequately con-trolled on OADs who were randomized to 1-3 daily injections (inj) of insulin lispro Mix25 or insulin glargine alone or with 1-3 daily inj of insulin lispro. In this post-hoc analysis, glycemic profiles of lispro Mix25-treated patients were analyzed by number of inj (N=38, 72, 63) with study sequence (din-ner, breakfast, lunch) and by ethnicity (Caucasians=36; Asians=77; Hispan-ics=60).

Results: At baseline, pre- and postprandial glycemic levels (Figure) and A1C (1 inj=8.8, 2 inj=8.9, 3 inj=9.1%) were higher with more inj. At week 48, glycemic profiles and A1C (7.3, 7.2, 7.3%) were similar for 3 insulin regimens. Total daily insulin dose increased with number of inj (23.0, 51.4, 78.6 u/d), but hypoglycemia rate decreased (33.4, 21.3, 16.3 events/patient/year). Similar trends were observed across ethnicities; however, with different propor-tions of patients on 1-3 insulin doses and hypoglycemia rates.

Conclusion: Progressive increase in number of inj of lispro Mix25 is an alternative simple insulin regimen allowing patients of different ethnicities to reach good glycemic control with minimal number of inj and no increase in hypoglycemia rate.

Supported By: Eli Lilly and Company

2359‑PUBPredictive Factors for Achieving Glycemic Control in People with Type 2 Diabetes (T2D) in Real Clinical PracticeTIRTHANKAR CHAUDHURY, ABDULQAWI AL MANSARI, YOUSSEF OBEID, NAJAMUL ISLAM, MOHAMMED FARIDUDDIN, AHMED HASSOUN, KHIER DJA-BALLAH, MOJTABA MALEK, Kolkata, India, Jeddah, Saudi Arabia, Beirut, Lebanon, Karachi, Pakistan, Dhaka, Bangladesh, Dubai, United Arab Emirates, Paris, France, Teheran, Islamic Republic of Iran

Current ADA/EASD position statement recommend to individualize both treatment targets and treatment strategies in inadequately controlled pts by oral glucose-lowering drugs (OGLDs) to decrease the burden of diabetes-related complications. We conducted a 12 months real-world practice study from October 2012 to January 2015 in 10 developing countries. The main objective of the study was to assess predictive factors for achieving the glycemic HbA1c at 6 months targeted by the treating physician in adults with T2D requiring insulin initiation, titration and/or intensification. There were 2,704 included eligible pts (mean (SD) age: 54.6 (10.6) years, BMI: 28.7 (5.4) kg/m2; Caucasian: 46.1%, T2D duration: 10.1 (6.7) years) with poor glycemic control (mean (SD) HbA1c: 9.7 (1.8)%, FBG: 196.8 (60.4) mg/dL). At baseline, 63.3% were treated with OGLDs alone, 27.9% with OGLD + insulin and 8.8% with insulin alone (basal [B]: 38.8%, premix: 35.6%, basal + prandial [BP]: 17.1%; N=931). From baseline to the end of study, the proportion of pts receiving OGLDs + insulin, B, and BP increased (85.4%, 71.2%; and 25.1% respectively) as the mean daily doses of B (16.5 to 21.9 U) and BP (56.1 to 61.9 U). At 6 months, advanced age, Caucasian ethnicity, shorter duration of T2D

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(>10 vs. 1 year), lower HbA1c at baseline (≥ 8.5% vs. <7%) (p≤0.0001) and no intake of OGLD (none vs. 2, p=0.02) were predictive factors for achieving gly-cemic goal as targeted by the treating physician. Absence of high blood pres-sure (p=0.0479) and use of basal insulin therapy (p<0.0001) were additional significant predictors identified at 12 months. Absolute changes in the mean HbA1c of -1.7% and -2% were observed from baseline to 6 and 12 months respectively. Along with some well-known predictive factors (shorter T2D duration, lower baseline HbA1c, no hypertension), this real world study in developing countries suggested that insulin regimen treatment initiation and/or intensification allowed pts to achieve a better glycemic control.

Supported By: Sanofi

2360‑PUBInsulin Pharmacodynamics during Follicular and Luteal Phases of Menstrual CycleEDA CENGIZ, WILLIAM TAMBORLANE, NEHA PATEL, JENNIFER SHERR, MICHELLE VANNAME, AMY STEFFEN, JENNIFER FINNEGAN, EILEEN TICHY, LORI CARRIA, ANDREA URBAN, SIRMEN KIZILCAN, SONALI SAXENA, NITIN SUKU-MAR, STUART WEINZIMER, New Haven, CT, Izmir, Turkey

Impact of menstrual cycle on insulin action in females with type 1 dia-betes. Insulin action during different phases of the menstrual cycle (MC) has not been well investigated and is associated with unpredictable blood glucose fluctuations each month in females with type 1 diabetes (T1D). To assess how the phase of the MC affects insulin action, we characterized the pharmacodynamic properties of rapid-acting insulin analogs using the eug-lycemic clamp technique after a single, subcutaneous dose of insulin aspart (0.2u/kg) in a randomized order, cross-over study conducted during both the luteal phase (LP) and follicular phase (FP).

Sixteen subjects have been enrolled, and to date, five (age 23±8 yrs, HbA1c 7.0±1%, duration of T1D 14±8 yrs, insulin dose 0.8±0.1 u/kg/day) have com-pleted both insulin action studies. As demonstrated in the Table, the average glucose infusion rate (GIRmean), maximum glucose infusion rate (GIRmax), and the area under the curve for GIR (AUCGIR 0-300min) are significantly decreased during the LP as compared to the FP. The time to reach maximum GIR (TGIRmax) was not significantly different. These preliminary results describe significant differences in insulin pharmacodynamics during different phases of the MC, with almost 50% reduction in glucodynamic action during LP, underscoring the importance of devising MC adjusted insulin treatment for better man-agement of T1D in females.

Table.

Pharmacodynamic Measures (mean±SD), (n=5)

Follicular Phase Luteal Phase p

GIRmean (mg/kg/min) 3.7±0.9 2.2±0.8 0.008GIRmax (mg/kg/min) 6.8±2.0 4.5±1.2 0.001T GIRmax (min) 84±46 110±51 0.5AUC GIR 0-300min (mg/kg) 1128±282 575±74 0.007

Supported By: The Leona M. and Harry B. Helmsley Charitable Trust

2361‑PUBThe Mechanics of Subcutaneous Insulin AbsorptionSPENCER T. FRANK, LING HINSHAW, RITA BASU, ANDREW J. SZERI, ANANDA BASU, Berkeley, CA, Rochester, MN

A key component of a successful artificial pancreas controller is its ability to predict the rate of insulin absorption. Particularly, if subcutaneously injected insulin reaches the bloodstream significantly faster or slower than nominal rates, hypoglycemia or hyperglycemia may result. For this reason we study the factors that impact the rate of insulin absorption from the subcutaneous tissue by relating tissue perfusion (i.e., tissue blood flow) to insulin absorption rates. We validate this relationship on two cohorts of T1D subjects: resting subjects (n=20, age = 42 ± 14 years, hemoglobin A1c = 7.2 ± 0.6%) and subjects exercising at 50% V02 max for 75 minutes (n=14, age = 45 ± 13 years, hemo-globin A1c = 7.6 ± 0.7%). Each cohort underwent a mixed meal tolerance test with a subcutaneous bolus of insulin pumped at mealtime with plasma insu-lin concentrations measured against time. Utilizing average tissue perfusion rates and average capillary permeability found in literature, our early results indicate that insulin concentration predictions for an average resting patient and an average exercising patient are close to experiments. Additionally, we show that tissue blood perfusion rates during exercise account for the acceler-ated rate of insulin absorption-an important phenomenon to capture because it helps to ensure safe glucose ranges during and after exercise.

Supported By: National Institutes of Health; National Science Foundation

2362‑PUBThe Impact of Baseline BMI and HbA1c on Glycemic Control after Treatment with Mealtime Fast‑Acting Insulin Aspart in People with Type 1 DiabetesDAVID RUSSELL-JONES, SIMON R. HELLER, VINCENT C. WOO, VINAY BABU, CLAUS DETHLEFSEN, CHANTAL MATHIEU, Guildford, United Kingdom, Sheffield, United Kingdom, Winnipeg, MB, Canada, Søborg, Denmark, Leuven, Belgium

Onset 1 was a 26-week, randomized trial evaluating the efficacy and safety of fast-acting insulin aspart (faster aspart) in adults with type 1 diabe-tes (T1D). Patients were randomized to double-blind mealtime faster aspart (n=381), insulin aspart (IAsp; n=380) or open-label post-meal faster aspart (n=382); each with insulin detemir. This post-hoc analysis investigated the impact of baseline body mass index (BMI; subgroups: <25, 25-30, ≥30 kg/m2) and HbA1c (subgroups: ≤7.5%, 7.5-8.0%, ≥8.0%) on glycemic control with mealtime faster aspart and IAsp.

In the overall population, change in HbA1c after 26 weeks was non-inferior (0.4% limit) for mealtime faster aspart vs. IAsp, with an estimated treatment difference (ETD [95% CI]) of −0.15% (−0.23;-0.07). ETD for change in HbA1c was similar across analyzed BMI and HbA1c subgroups (Table). No major dif-ferences between treatments were observed for severe or blood glucose (BG)-confirmed hypoglycemia across subgroups (Table). Total daily insulin dose was similar in patients across all baseline HbA1c groups and the BMI <25 or 25-30 kg/m2 groups, but was significantly lower with mealtime faster aspart compared with IAsp in subjects with baseline BMI >30 kg/m2 (Table).

In conclusion, treatment difference between faster aspart and IAsp for glycemic control in people with T1D was not affected by baseline BMI or baseline HbA1c.

Supported By: Novo Nordisk A/S

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2364‑PUBAnti‑insulin Antibodies and Immune Adverse Events with SAR342434 Insulin Lispro Compared with Humalog Insulin Lispro in People with DiabetesPHILIP D. HOME, KARL-MICHAEL DERWAHL, MONIKA ZIEMEN, KARIN WER-NICKE-PANTEN, SUZANNE PIERRE, YVONNE KIRCHHEIN, SATISH K. GARG, Newcastle upon Tyne, United Kingdom, Berlin, Germany, Frankfurt, Germany, Paris, France, Aurora, CO

SAR342434 (insulin lispro, Sanofi) is a follow-on (biosimilar) of insulin lis-pro (Humalog®, Lilly). Both phase 3 studies in people with type 1 (T1DM; 12-month study, SORELLA 1) and type 2 diabetes (T2DM; 6-month study, SORELLA 2) were randomized (1:1), open label, parallel-group studies com-paring the efficacy and safety of these two insulins in combination with insu-lin glargine (U100; Lantus®). Baseline antibody positivity was similar for both insulins, but higher in T1DM than in T2DM. In both studies, the percentage of people newly positive for AIAs in the two treatment groups, or having a ≥4-fold increase in AIA titer, was not found to differ (Table). No relationship was observed between highest individual titers and HbA1c change, insu-lin dose, hypoglycemia, hypersensitivity or injection site reactions. Formal adjudications of increase in HbA1c >1.0% or unexplained increase in insulin dose found no association with AIAs. Hypersensitivity events and events adjudicated as allergic reactions were few and did not differ between the two insulins (Table); none of them was suspected to be AIA mediated. Over-all efficacy/safety results in the studies did not differ (presented elsewhere). We conclude the follow-on insulin lispro SAR342434 had a similar immuno-genicity profile in people with T1DM and T2DM to originator insulin lispro.


2365‑PUBEfficacy and Safety of Insulin Degludec (IDeg) vs. Insulin Glargine U100 (IGlar) in Hispanic Patients with Type 2 Diabetes (T2D)LOUIS B. CHAYKIN, ANUJ BHARGAVA, CAROL H. WYSHAM, TRINE ABRAHA-MSEN, MICHIEL VAN LEEUWEN, RAYMOND DE LA ROSA, Bradenton, FL, Des Moines, IA, Spokane, WA, Søborg, Denmark, Paducah, KY

The risk of developing T2D is higher in Hispanic populations compared with non-Hispanic Caucasians. The safety and efficacy of IDeg once daily (OD) vs. IGlar OD was assessed post-hoc in a subgroup of Hispanic patients with T2D in a 64-week, double-blind, treat-to-target, crossover trial (SWITCH 2; NCT02030600). Of the patients in SWITCH 2 (n=721), 36% were Hispanic (IDeg/IGlar n=140; IGlar/IDeg n=122). Baseline characteristics including A1c were comparable between treatments. A1c reductions with IDeg were simi-lar to IGlar (ETD 0.03% [-0.21; 0.27]95% CI and 0.15% [-0.09; 0.39]95% CI after period 1 and 2, respectively). The rate of overall symptomatic (severe [requir-ing third-party assistance and external adjudication] or blood glucose [<56 mg/dL] confirmed) hypoglycemia in the maintenance period (after a 16-week titration period) was numerically lower with IDeg than IGlar. The rate of noc-turnal symptomatic (00:01-05:59, both inclusive) hypoglycemia in the main-tenance period was significantly lower with IDeg vs. IGlar; p<0.05 (Figure). Results were similar in the full treatment period. Adverse events (AE) and serious AEs were comparable between treatments.

In conclusion, results in a Hispanic subpopulation are consistent with the overall trial results; IDeg and IGlar lead to good glycemic control with a lower risk of hypoglycemia with IDeg vs. IGlar in Hispanic patients with T2D.


2366‑PUBPooled Analysis of Seven Randomized Controlled Trials with Insulin Glargine 100 U/mL Stratified by Type of Meal‑Time Insulin in Adults with T1DMGEREMIA B. BOLLI, DAVID R. OWENS, GREG FULCHER, BRIAN M. FRIER, MEI ZHANG, WOLFGANG LANDGRAF, DEMET OZKAYA, PHILIP D. HOME, Perugia, Italy, Cardiff, United Kingdom, Sydney, Australia, Edinburgh, United Kingdom, King of Prussia, PA, Frankfurt, Germany, Paris, France, Newcastle upon Tyne, United Kingdom

In order to define more precisely the efficacy and safety outcomes of insu-lin glargine 100U/ml (Gla-100) in people with T1DM, standardized patient-level data were pooled from seven RCTs (26-30 weeks duration) when using QD Gla-100 together with either regular human insulin (RHI) or rapid-acting insulin analogs (RAI). HbA1c, FPG, body weight, insulin dose and hypogly-cemia were assessed descriptively through to study endpoint. Overall, 1,282 participants (49% male) on Gla-100 and prandial insulin (RHI n=694, RAI n=580, unknown n=8) were included. They were (mean ± SD) aged 41 ± 13 years, diabetes duration 16 ± 11 years, and BMI 24.5 ± 3.8 kg/m². Mean baseline and endpoint Gla-100 doses were similar (0.31 ± 0.15 and 0.29 ± 0.13 U/kg), while total insulin dose was 0.70 ± 0.23 U/kg at baseline and did not change. Clinical outcomes are shown in the Table. HbA1c reduction was small with both RHI and RAI, with a low percentage (14%) of people reaching

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target of <7.0%. Hypoglycemia affected a high proportion of people (overall, 89%; nocturnal 61%), but hypoglycemia requiring assistance only 11%. This pooled analysis in adults with T1DM confirms that, in the presence of a high incidence and rate of hypoglycemia (overall, nocturnal), only a minority of people reached glycemic targets, likely due to insufficient optimization of basal insulin and independent of type of meal-time insulin.


2367‑PUBObservational Registry of Basal Insulin Treatment (ORBIT) in Patients with Type 2 Diabetes in China: Safety and Hypoglycemia PredictorsTINGTING ZHANG, LINONG JI, YAN GAO, PUHONG ZHANG, DONGSHAN ZHU, HENG ZHANG, XIAN LI, JIACHAO JI, XIAOHUI GUO, Beijing, China

Background: Basal insulin (BI) has been widely used in clinical practice for diabetes therapy. The Observational Registry of BI Treatment (ORBIT) study was designed to evaluate the safety of BI after initiation in real-world practice settings in China.

Methods: Patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral hypoglycemic agents (OHAs) from 8 geographic regions and 2 hospital tiers in China initiated BI treatment. Data for body weight and hypoglycemic episodes were collected at baseline, 3 and 6 months. Serious adverse events (SAEs) were collected at 3 and 6 months.

Results: BI use did not induce significant weight gain; long-acting basal insulin analogs, especially insulin detemir, caused less weight gain than that of NPH insulin. At the end of this study, general hypoglycemia was reported in 7.7% and severe hypoglycemia was 0.3%. General hypoglycemia had a slightly increasing trend (from 1.62 up to 1.79 times/patient/year) and severe hypoglycemic event had a slightly decreasing trend (from 0.05 down to 0.03 times/patient/year). Probable symptomatic hypoglycemia events had the highest proportion of total hypoglycemia events. The increase of hypoglyce-mia was mainly seen in patients taking NPH insulin and insulin detemir. Age, inpatient or outpatient status, body mass index, HbA1c at baseline and end of study, T2DM duration, microvascular complications, BI type, combination with insulin secretagogues, SMBG times, and insulin dosage all predicted hypoglycemia. In total, 3.5% of patients have at least one SAE during the study period. Most SAEs of patients (86.8%) were deemed unrelated to OHAs or insulin treatment.

Conclusions: In the ORBIT study, BI use, especially that of insulin detemir and insulin glargine, was associated with minimal weight gain and good safety outcomes for hypoglycemia in patients with T2DM in real-world set-tings of China.

Supported By: Sanofi China

2368‑PUBBasal‑Bolus vs. Other Insulin Strategies in a “Real World” Hospital Setting: Association with Glucose Control and Patient OutcomesARCHANA R. SADHU, AISHA VADHARIYA, BHARGAVI PATHAM, HARLAN SPARROW, MICHAEL L. JOHNSON, Houston, TX

Guidelines on inpatient hyperglycemia in noncritically ill patients recom-mend using basal bolus insulin (BB) therapy instead of sliding scale (SS) alone. However, limited outcomes data exist from large scale “real world” settings. We retrospectively reviewed 4,670 admissions between Jan 2013 and Sep 2015. Patients ≥18 years who received subcutaneous insulin ≥ 75% of the hospital stay but not any IV insulin were included. Insulin therapy was grouped into 3 types: BB only (n=842), SS only (n=1428), or Mixed (both BB

and SS on various days, n=2459). In our first analysis, we identified factors associated with choice of insulin therapy. Now we evaluate glucose control and patient outcomes with a propensity score analysis adjusting for those factors. A patient day was defined by point of care glucose (POC) in mg/dL as hypoglycemic (<70), hyperglycemic (mean >180) or euglycemic (none <70 and mean ≤180). Patient outcomes were mortality, length of stay (LOS) and readmission. Negative binomial regression analysis was used to determine unique factors associated with count of hyper-, hypo- and euglycemic days; linear regression was used to model log of LOS; logistic regression modeled 30 and 60 day readmission rates. Average POC was 30 mg/dL less for SS and 24 mg/dL less for Mixed than BB. SS had less hypo- and hyperglycemic days (P<0.001), while Mixed had more hypoglycemic days (P<0.001) than BB. Mortality rates were: 0.0% BB; 0.07% SS (n=1); 0.45% Mixed (n=11). BB had similar average LOS as SS but 1.7 days (32%) lower than Mixed (P<0.0001). Readmission rates did not differ across groups. BB was used in more complex patients, and had worse glycemic control than SS, but with equivalent patient outcomes. BB had less hypoglycemia but not hyperglycemia, and significantly lower LOS than Mixed, suggesting that glycemic control alone may not fully explain the improved outcomes with BB. More investigation is needed to understand the effects of BB, particularly in mixed insulin regimens.

2369‑PUBBody Mass Index and Age Are Independent Determinants for Basal Insulin Requirement in Patients with Type 1 DiabetesAKIO KURODA, MUNEHIDE MATSUHISA, Tokushima, Japan

Background and Aim: The determinant for basal insulin requirement in the daily life has not been well documented in patients with type 1 diabetes. We investigated the basal insulin dose requirement and associated factors in patients with type 1 diabetes.

Methods: Fifty-six inpatients with type 1 diabetes treated with sub-cutaneous insulin injections were enrolled. All patients were hospital-ized because of blood glucose control and education from 2011 to 2016 in Tokushima University Hospital and were obtained the written informed consent for this study. They were treated with foods under the control of dietitian. Basal insulin dose were adjusted to maintain the blood glucose at the same values before sleep and before breakfast. Clinical characteristics and basal insulin requirement were investigated.

Results: Twenty-two male and 34 female patients were enrolled (Age, 53.0±16.4 years; BMI, 23.1±4.2; HbA1c 8.9±1.9%). Total daily dose of insulin (TDD) was 36.1±16.9 units (0.62±0.22 units/kg). Total daily basal insulin dose was 9.2±6.1 (25% of TDD) units. Plasma C-peptide was 0.29±0.46 ng/mL. Total insulin requirement in insulin-deficient (C-peptide<0.2ng/mL) patients were 32 among 56 patients and total basal insulin dose was 27.2±0.11% of TDD. The ratio of total basal dose to TDD was significantly correlated with BMI (r=0.361, p<0.01), plasma C-peptide (r=-0.334, p<0.05), age (r=-0.363, p<0.05), and HbA1c (r=0.277, p<0.05). BMI (p<0.01) and age (p<0.05) were the significant factors for the determinant of % basal insulin dose according to the multiple regression analysis.

Conclusion: Low basal insulin requirement was associated with good gly-cemic control, and was determined by low BMI and age.

2370‑PUBBaseline Red Blood Cell Distribution Widths Indicate Long‑Term Glycemic Remission in Patients with Type 2 DiabetesLIJUAN XU, LIANGJIAO WANG, XINWEI HUANG, YANBING LI, Guangzhou, China

Aims: Short-term continuous subcutaneous insulin infusion (CSII) has been shown to be effective for inducing long-term drug-free euglycemic remission in nearly half patients with newly diagnosed type 2 diabetes; yet, predictors of remission are still unsettled. We explored whether red blood cell distribu-tion widths (RDWs), a routinely checked parameter of complete blood cell counts, was an indicator of long-term euglycemia remission.

Methods: We analyzed the original data from patients enrolled in three randomized control trials from 2002 to 2014 with similar inclusion and exclusion criteria. CSII was administered to drug-naïve patients with newly diagnosed type 2 diabetes. The insulin dosage was titrated to achieve and maintain euglycemia for 2 weeks.

Results: A total of 185 patients were involved. Ninety-eight patients (52.97%) who achieved and maintained euglycemia for at least 12 months were classified as the remission group, and the other 87 patients as the non-remission group. Patients in remission group had a relatively lower value for RDWs (38.82±2.76 vs. 39.89±2.78 fL, p=0.017) compared with those in non-remission group at baseline. A graded decrease of remission rate (67.50%, 55.00%, 53.66% and 30.77% for Quartile 1 to Quartile 4 respectively, P<0.05) was observed with the increasing of RDWs. The risk

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of hyperglycemic relapse was significantly increased for those in the high-est quartile compared with the lowest (hazard ratio=2.68; 95% CI, 1.38 to 5.22). In addition, Patients who achieved euglycemia within 7 days (hazard ratio=0.60, p=0.046) or a better fasting glucose (6.12±1.38 vs. 6.67±1.29 mmol/L, p<0.001) after therapy had a preferable remission rate.

Conclusions: Patients with lower baseline RDWs are more likely to obtain a one-year euglycemia remission after short-term CSII. A faster normaliza-tion of glucose during treatment and a lower fasting glucose after therapy are beneficial for improving the long-term glucose control.

2371‑PUBThe Impact of Age on Real‑World Titration of Insulin Glargine 100 U/mL in Patients with Type 2 Diabetes Poorly Controlled on Oral Antidiabetic DrugsANDREAS FRITSCHE, HELMUT ANDERTEN, ANJA BORCK, KATRIN PEGELOW, MARTIN PFOHL, STEFAN PSCHERER, JOCHEN SEUFERT, Tübingen, Germany, Hildesheim, Germany, Berlin, Germany, Duisburg, Germany, Weimar, Germany, Freiburg, Germany

Adding insulin glargine 100 U/ml (Gla-100) improves glycemic control in patients (pts) previously not controlled on OADs. Little is known how age might impact titration of Gla-100 and how this may affect a primary endpoint (PE) of a FBG ≤110 mg/dL or reaching an individual HbA1c target. TOP-1 is a prospective observational study with a 12 months follow-up in pts with T2DM attending GP offices in Germany. Pts on OADs with or without basal insulin other than Gla-100 with an HbA1c of 7.5-10% whose physicians had decided to use insulin Gla-100, were included in the study. Pts (n=2,462) were grouped by age: <65 yrs (45.6%), 65-74 yrs (31.3%), ≥75 yrs (23.1%). The mean individual HbA1c targets were 6.8%, 6.9% and 7.1%, respec-tively. Elderly pts ≥75 yrs were less often male (43.8 vs. 58.7%), had a lower BMI (29.7 vs. 32.0 kg/m2), a lower FBG (181.1 vs. 186.5 mg/dl) and a similar HbA1c (8.5 vs. 8.6%) at baseline compared to pts <65 years. Insulin titration was performed according to Fritsche (46.7%), Davies (28.9%) or individu-ally (22.0%) with a trend for an increased use of the Fritsche scheme in the elderly (51.1% ≥75 years vs. 45.8% <65 years). The PE was equally often met across age groups being reached in 63.6, 68.2, and 66.9% of pts, respec-tively (p=n.s.). While there was no differential response with respect to the FBG (p=n.s. at 12 months), more elderly pts (54.7%) and more pts 65-74 years (54.3%) reached their individual HbA1c target than those younger (46.0%) at 6 and 12 months (p≤0.02 for the pairwise comparison). Pts ≥75 yrs had a lesser drop of HbA1c (Δ1.2% vs. Δ1.5%) and FBG (Δ 53.4 mg/dl vs. Δ 64.1 mg/dl) at 12 months than younger pts. Confirmed, symptomatic hypoglycemia was documented in 0.3%, 0.3%, and 0.5% of pts (0.2%, 0.4% and 0.4% dur-ing night) with increasing age with no difference between groups. This study shows that the targeted and achieved HbA1c levels varied according to age and while being less stringent in elderly subjects it was more frequently met.

Supported By: Sanofi Aventis Deutschland GmbH

2372‑PUBReal‑World Titration of Insulin Glargine 100 U/mL in Patients with Type 2 Diabetes Poorly Controlled on Oral Antidiabetic DrugsJOCHEN SEUFERT, HELMUT ANDERTEN, ANJA BORCK, ANDREAS FRITSCHE, KATRIN PEGELOW, STEFAN PSCHERER, MARTIN PFOHL, Freiburg, Germany, Hildesheim, Germany, Berlin, Germany, Tübingen, Germany, Weimar, Germany, Duisburg, Germany

Adding insulin glargine 100 U/mL (Gla-100) improves glycemic control in patients (pts) previously not controlled on OADs. While there have been titra-tion schemes suggested, real-world titration of basal insulin is unknown. TOP-1 is a prospective observational titration study with a 12 months FU in pts with T2DM attending GP offices in Germany. Pts on OADs with or with-out basal insulin other than Gla-100 with an HbA1c of 7.5-10%, whose physi-cians had decided to use insulin Gla-100, were included. Pts (n=2,308) were grouped into titration groups: no titration (0 U; 39.2%) within the first month, titration +1-4 U (31.0%), +5-8 U (17.7%), and >8 U (12.1%). The mean individual HbA1c target was 6.9% in all groups except the > 8 U group (7.0%). Pts with forced titration (>8 U) were younger (63.8 vs. 66.0 yrs), more often female (58.1 vs. 49.8%), had a higher BMI (33.2 vs. 30.6 kg/m2), and had a higher FBG (201.0 vs. 179.4 mg/dl) as well as higher HbA1c (8.8 vs. 8.4%) at base-line compared to no titration. Pts with forced titration had a steeper mean drop of HbA1c (Δ1.6% vs. Δ1.2%) and FBG (Δ 75.1 mg/dl vs. Δ 51.2 mg/dl) at 12 months than patients with no titration. The primary endpoint (FBG ≤110 mg/dL or an individual HbA1c target) was, however, equally often met in titra-tion groups with no, 1-4 U, 5-8 U and >8 U, being reached in 65.0, 68.4, 66.7, and 62.9% of pts, respectively (p=n.s.). A combination of FBG ≤110 mg/dL and an individual HbA1c target was met at 12 months more often in pts with

an increase of 5-8 U (27.2% vs. 20.1%; p=0.03) and > 8 U (26.2% vs. 20.1%; p=0.02) compared to no titration. Confirmed, symptomatic hypoglycemia was documented in 1.5%, 2.4%, 1.2%, and 2.2% of pts in ascending order of titration with no difference between groups. The majority of pts in clinical practice were titrated slow and treatment was not intensified early enough and stopped as soon as a fasting blood glucose of about 130 mg/dl was achieved.

Supported By: Sanofi Aventis Deutschland GmbH

2373‑PUBInsulin Requirement in Well‑Controlled Type 1 Diabetes Patients with Continuous Subcutaneous Insulin Infusion or Multiple Daily Injection TherapyPING LING, JINHUA YAN, QINGWEI XIE, LILING QIU, SIHUI LUO, XUEYING ZHENG, HEYING AI, DAIZHI YANG, YAN WU, JIANCAI LIN, FUNENG WANG, JIANNENG WU, SHAOQING LI, BIN YAO, JIANPING WENG, Guangzhou, China

Objective: Continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) are the recommended therapies for patients with type 1 diabetes (T1D). The aim of this study was to investigate the insulin require-ment in patients with T1D achieving target glycemic control with CSII or MDI therapy under real-life condition.

Methods: In this multicenter registry study, a total of 673 adults (≥18 years old) and 285 children T1D (<18 years old) with CSII or MDI therapy were enrolled and followed-up for at least one year. The total insulin dose (TDD), the total basal dose (TBD) and percentage of TBD to TDD (%TBD) were collected after meeting the age-specific targets of HbA1c (<7.0% for adult, <7.5% for children) at least for 6 months.

Results: A total of 218 adults (age 33.6±11.1years, BMI 20.9±2.1kg/m2) and 68 children (age 11.1±4.3years, BMI 17.1±2.1 kg/m2) patients met the above criteria, with the durations of diabetes 4.9 (2.1,9.6) years and 1.2 (1.0,3.5) years, respectively. After 1 year follow-up, HbA1c were 6.23±0.51% and 6.72±0.47% in adult and children group respectively. In adult patients, the TDD was 0.62±0.24 IU/kg and 0.70±0.23 IU/kg in patients treated with CSII and MDI (P=0.013), respectively. The TBD was 0.22±0.15 IU/kg and 0.18±0.12 IU/kg in patients with CSII and MDI (P=0.022), respectively. In children patients, the TDD was 0.72±0.29 IU/kg and 0.89±0.25 IU/kg in patients with CSII and MDI (P=0.012), respectively, while the TBD was 0.35±0.15 IU/kg and 0.26±0.11 IU/kg (P=0.017) in patients with CSII and MDI, respectively. %TBD was higher in CSII group than that in MDI group (44±12% vs. 34±10%, p<0.001 in adults; 46±12% vs. 30±9%, p<0.001 in children).

Conclusions: The results indicated that under real-life condition, the basal insulin requirements were less than 50%, with higher rate by CSII than by MDI in Chinese patients with T1D whose HbA1c reached the age-specific targets.

Supported By: National Health and Family Planning Commission Foundation for Public Welfare Industry Research (201502011); Science and Technology Planning Project of Guangdong Province (2014A020212065, 2015A030401034); Sun Yat-Sen University (2007030)

2374‑PUBClinical Predictors of the Need for Further Treatment Escalation in Patients with Type 2 Diabetes on Basal Insulin TherapyMICHAEL A. NAUCK, CHRISTINA BUCHHOLZ, MELANIE KAHLE, JURIS MEIER, Bochum, Germany, Bad Lauterberg, Germany

Patients with type 2 diabetes can achieve adequate glycemic control with basal insulin/oral glucose-lowering agents, others need further treatment intensification. Our aim was to identify clinical characteristics that distin-guished between these two patient populations. During one calendar year, 213 out of 1042 consecutively hospitalized type 2-diabetic patients were treated with basal insulin/oral agents. This led to satisfactory glucose profiles in 156 patients (73.2%), for whom continuation of basal insulin treatment was recommended, while in 57 (26.8%), intensification of treat-ment was deemed necessary (clinical decision) and initiated. We compared patients’ characteristics, the insulin titration process, and resulting in-hospital plasma glucose profiles between these groups. Patients needing intensified regimens (adding meal-time insulin or GLP-1 receptor agonists or switching to premixed insulin) had higher initial HbA1c values (10.1 ± 1.7 vs. 9.5 ± 1.9%, p = 0.028), were more likely to be female (49.1 vs. 25.0%, p = 0.0014) and more obese, and required more basal insulin to achieve fast-ing plasma glucose targets (62 ± 40 vs. 39 ± 27 IU/d, p < 0.0001. In both patient groups, basal insulin was able to reduce fasting plasma glucose into the target range (119 ± 23 vs. 103 ± 15 mg/dl), however, in those need-ing treatment intensification, post-prandial plasma glucose remained sub-stantially higher after basal insulin titration (226 ± 36 vs.169 ± 28 mg/dl, p < 0.0001). After therapy intensification (i.e., before hospital discharge),

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similar plasma glucose profiles were reached in both groups. Those needing intensification had significantly longer hospital stays.

In conclusion, basal insulin therapy can provide satisfactory glucose con-trol in more than 70% of patients with type 2 diabetes. Long diabetes dura-tion, obesity, insulin resistance and female sex are associated with the need for further treatment intensification.

2375‑PUBThe Final Dose of Basal Insulin Needed for Effective Blood Glucose Control and Determinants in Type 2 Diabetes Mellitus in China: Results from Observational Registry of Basal Insulin Treatment (ORBIT)LEILI GAO, LINONG JI, PUHONG ZHANG, Beijing, China

Background: The efficacy of basal insulin (BI) for adequate glycemic con-trol in patients with type 2 diabetes mellitus (T2DM) has been well docu-mented by randomized clinical trials. This post-hoc analysis of the ORBIT study was performed to explore the final dose of BI used in insulin-naïve T2DM patients and determine the patient characteristics that affect the final dose of BI in the setting of real-world clinics in China.

Methods: This multicenter observational registry enrolled 19,894 adult T2DM patients with inadequately controlled hyperglycemia and treated with oral antidiabetic drugs (OADs) from 209 hospitals across all 8 regions in Mainland China. Of these patients, 5191 who continued to receive BI after 6 months and achieved HbA1c target (<7%) were analyzed. Patient character-istics including age, body weight, fasting plasma glucose (FPG), use of OADs and insulin (type and dose), glycemic control, and hypoglycemic episodes were recorded at baseline and 3- and 6-month follow-ups.

Results: The dose of BI needed for effective glycemic control was 0.20±0.08 IU/kg/day. High body mass index, high fasting plasma glucose, young age, longer duration of diabetes or OAD treatment, more number of OADs at baseline, and allocation to detemir and glargine were significant independent predictors for high dose of BI.

Conclusion: This post-hoc analysis of the ORBIT registry provides key information on the final dose of BI needed for effective glycemic control in Chinese T2DM patients. Furthermore, this study identified crucial patient characteristics that are significant determinants of the final dose of BI in a real-world setting.

2376‑PUBComparison of Clinical Outcomes in Inpatient Diabetes Manage‑ment by Endocrine Team and Non‑Endocrine Teams in Cardiac Sur‑gery PatientsJAGDEESH ULLAL, DAVID A. KLIMPL, ELIAS S. SIRAJ, Norfolk, VA, Baltimore, MD

Maintaining reasonable glycemic control in Coronary Artery Bypass Graft (CABG) patients has proven to improve outcomes. Our Endocrine Team (ET) is routinely consulted in patients with diabetes mellitus (DM) undergoing CABG where we use carbohydrate counting (CC) for prandial insulin dosing, which has been shown to improve glycemic control when compared to fixed dose (FD) bolus dosing. When we are not consulted, various non-endocrine teams (NET) manage the diabetes, using an FD bolus regimen.

This study was aimed at comparing key clinical outcomes and length of stay (LOS) between the 2 groups of patients managed by ET and NET. It was designed as a retrospective review of patients with DM who underwent CABG over a 5 year time frame.

A total of 3366 charts of patients with DM who underwent CABG were queried electronically. 1546 were excluded due to various exclusion criteria. This resulted in 473 patients in the ET group and 1347 patients in the NET group. Data below are presented as mean ± standard deviation, comparing the ET group vs. NET group.

The HbA1c was 8.2 ± 3 vs. 6.9 ± 2.4%. The LOS was 13.8 ± 10.9 days vs. 14.2 ± 10.5 days. The number of hyperglycemic events >180 mg/dl were 25.8 ± 23.0 vs. 18.0 ± 20.2. The number of hypoglycemic events (<70 mg/dl) were 2.8 ± 4.3 vs. 2.1 ± 3.7. Using a multivariate analysis, increasing age, HbA1c, and female gender were all associated with a longer LOS (P < 0.05). LOS was slightly lower (though non-significant) in the ET group, where CC was used compared to NET where FD was used. The frequency of both hyperglycemic and hypoglycemic episodes were significantly higher in the ET group com-pared to NET group (P <0.01).

In summary, our study showed that HbA1c, age and gender were major drivers of LOS. The LOS in the ET group was equal to that of the NET group, despite the possible confounding resulting from more complicated patients ending up in the ET service as demonstrated by a higher HbA1c, and more frequent hyperglycemic and hypoglycemic episodes.

2377‑PUBEffects of Gender on Short‑Term Intensive Insulin Therapy for Newly Diagnosed Type 2 DiabetesXUESI WAN, ZHIMIN HUANG, LIEHUA LIU, YANBING LI, Guangzhou, China

It has been demonstrated that patients with newly diagnosed type 2 dia-betes mellitus (T2DM) achieved drug-free glycaemic remission after short-term intensive Insulin treatment (IIT). It’s interesting that the male were bet-ter restored than the female. The purpose of this study is to clarify the effect and mechanism of gender on T2DM remission and related determinants. An observation of 160 patients with newly diagnosed T2DM (n=160,103 male, aged 50±10 ys, HbA1c 11±2.1%) after 2 weeks of CSII was studied diabetes remission rates. After one year of the termination of intensive therapy, there were 83% male and 65% female still in remission. The characteristics of male and female patients were compared in Table below. Data with nor-mally distributed variables showed as mean ± SD. Obviously, the ages at diagnosis of T2DM were much younger in male when compared with the female (47±10 ys vs. 54 ±9 ys). And waist-to-hip ratios were higher in the male. GHbA1c and BMI in the male group seemed to be higher but without significant difference. There were no differences in DM family history (43% vs. 48%), HOMA-β, HOMA-IR and average daily insulin dose between the two groups. Moreover, the single factor logistic regression showed the age significantly associated with T2DM remission (OR=0.95). These indicated that gender might affect the remission rate mainly by the age at diagnosis. Younger patients seem to have a more favorable outcome.

Table. Differences between Gender.Male Female

Before IIT After IIT Before IIT After IITBMI(kg/m2) 25.6±3.2 25.3±3.0 24.7±3.4 24.4±3.0waist-to-hip ratios 0.95±0.05 0.95±0.05 0.89±0.06 0.88±0.06GHbA1c(%) 11.2±2.0 9.6±1.6 10.5±2.1 9.1±1.6HOMA-β 22.5±16.6 67.2±52.0 26.3±20.8 63.0±40.8HOMA-IR 3.9±2.2 2.1±1.2 4.3±2.7 2.2±1.1average daily insulin dose 0.64±0.17 — 0.66±0.15 —

2378‑PUBPhysician and Patient Perspectives after Switching Current Basal Insulin to Insulin Degludec in Type 1 Diabetes Mellitus (T1DM) Patients with Previous HypoglycemiaEDURNE LECUMBERRI, MAITE ORTEGA, JOSÉ ANTONIO QUESADA, MARTA ITURREGUI, ALICIA ESTRELLA, CLOTILDE VAZQUEZ, DOMINGO OROZCO-BEL-TRAN, Madrid, Spain, Alicante, Spain

Introduction: Insulin analog Degludec has already demonstrated to reduce severe hypoglycemic events and to slightly improve glycemic control. How-ever, there is scarce data from real-life clinical practice studies about quality of life and fear of hypoglycemia in this group of patients.

Objectives: To assess efficacy, safety and patient perception of hypogly-cemia and quality of life after 6-month-treatment with insulin Degludec.

Material and Methods: Observational study. Variables: Efficacy (fasting glucose levels and A1c), safety (percentage of patients with hypoglycemia and number of hypoglycemic episodes), assessment of degree of hypogly-cemia fear (Hypoglycemia Fear Survey II (HFS-II)) and quality of life (visual analogue scale (VAS) of EQ-5D test). Student’s t-test for paired samples was used to evaluate changes in mean test punctuation.

Results: 101 T1DM patients were included. Fasting glucose (mg/dl) (163.4 vs. 132.7; -30.7 ± DE 66.7; p=0.006) and HbA1c (%) (7.78 vs. 7.59; -0,18 ± DE 0,66; p=0.000) reduction was observed. Reduction of percentage of patients with severe hypoglycemia (11.9 vs. 4%) and reduction in number of hypo-glycemic episodes (0.17 vs. 0.05; p=0.003) were observed. After the basal insulin switch the mean punctuation of the fear of hypoglycemia test HFS-II was significantly reduced (24.17 a 20.26; p<0.001), the mean punctuation in VAS was improved in some degree as well (71,6 a 73,9; p=0.081).

Conclusions: Insulin Degludec improves slightly glucose control in this group of type 1 DM patients. It reduces significantly the rate of severe hypo-glycemia reported by patients. They show less fear of having a hypoglycemic episode, this fact possibly being an indirect sign of the decrease of the fre-quency of them. Although it does not reach statistic significance, the mean score of VAS has slightly increased. This could be seen as a sign of a modest improvement in the perception of health status.

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CLINICAL THERAPEUTICS/NEW TECHNOLOGY—INSULIN DELIVERY SYSTEMS

CLINICAL THERAPEUTICS/NEW TECHNOLOGY—INSULIN DELIVERY SYSTEMS

2379‑PUB

2380‑PUBPredictive Low Glucose System in People with Type 1 Diabetes Hard to TreatDAVIDE BRANCATO, MATTIA FLERES, GABRIELLA SAURA, VITO AIELLO, ALES-SANDRO SCORSONE, ANNA DI NOTO, FRANCESCA PROVENZANO, LUCIA SPANO, VINCENZO PROVENZANO, Partinico, Italy

Aim: To study the effect of Predictive Low Glucose System (PLGS) in peo-ple with T1D who show persistently high levels of glycemic variability and/or A1c, despite efforts to improve diabetes management.

Methodology: From 120 people with T1D using PLGS, we retrospectively selected 20 consecutive subjects (9 females, 11 males; age, mean ± SD = 23.3 ± 14.7) who showed, during the last year and despite repeated and intensive efforts to improve diabetes management: 1) ≥ 1 severe hypoglyce-mia and 2) A1c ≥ 8.0% or ≥ 1 hospital admissions for diabetes acute compli-cations. Main outcome were, before and 3 months after the commencement of PLGS: glycemic variability (GV), expressed as SD from the mean glucose concentration measured by continuous glucose monitoring (CGM); % of time below glycemia < 70 mg% (TBG), measured by CGM; and A1c.

Results: GV was significantly reduced from 56.2 ± 13.9 to 50.1 ± 10.2 mg% (p < 0.05), TBG improved from 0.37 ± 0.71 to 0.13 ± 0.23% (p < 0.05), and A1c decreased from 8.0 ± 1.5 to 7.4 ± 0.6% (p < 0.05). No severe hypoglycemia occurred during the trimester of observation.

Discussion and Conclusions: T1D is not an easy condition to treat and, despite the efforts to optimize management through intensive education programs, use of most updated insulin analogues, insulin pumps and CGM, a substantial proportion of people does not achieve treatment goals. Our pilot study suggests, in T1D hard to treat, that PLGS could improve GV and time spent into hypoglycemia while decreasing A1c, thus allowing the achieve-ment of treatment goals.

2381‑PUB

2382‑PUBRegulation of Blood Glucose Level in Type 1 Diabetes by Micropro‑cessor‑Controlled Automated Implanted PatchWI KIM, SUWANG JANG, SANGKEON PARK, BUMKEUN PARK, JUNGHO YOON, Daejeon, Republic of Korea

Currently there have been lots of trials by controlling blood glucose level by using automated implanted insulin secretion system in IDDM patients. Most of the automated insulin secretion systems are carried out by using air based or spring buttons to insert insulin and lower down blood glucose level when concentration is over 120mg/dl. However, depend on the sensitivity and the pressure controlled by patient, insulin concentration is inaccurately secreted by patients. Overall object of this study was to controlling blood glucose level to IDDM patient by inserting dome-shape insulin secreting implanted patch onto left arm. To accomplish this, we made dome-shaped patch assembled with micro motor with 20 teeth of gear system, which represent 1 tooth for 0.5 units, microprocessor to record and send blood and glucose data to wireless PC or smart device, insulin capsule and sliding door to secret insulin form capsule with insulin and glucose sensing crystal attached at lower end. Initial In vivo examination was done by using strepto-zotocin treated C57BL/6J with surgically implanted dome-shaped patch. We also confirmed insulin and glucose sensing from dome-shaped patch by L6 skeletal cell and adipocyte glucose intake level. Blood glucose level of STZ treated mice were in between 180mg/dl to 400mg/dl with accompanied by pancreas islet cell destruction. Concentration and timing of insulin secretion was programmed into microprocessor when blood glucose level was more than 120mg/dl and stop secreting insulin when blood glucose level reaches 120mg/dl. One week later patch implanting surgery, blood glucose level was checked every one hour and patched mice drop down 80mg/dl to 120mg/dl.

In summary, we believe real time controlling blood glucose level is more efficient than one time insulin injection. In particular, we observed patch with gear control insulin secretion accuracy was less than 0.01% concentra-tion error after 2,000 secretions.

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CLINICAL THERAPEUTICS/NEW TECHNOLOGY—NONINSULIN INJECTABLES

2383‑PUBInsulin Pump Therapy in Patients with Diabetes Mellitus Type 2: A Survey of Patient ExpectationsFELIX ABERER, TINA POETTLER, HARALD SOURIJ, NORBERT TRIPOLT, SEBAS-TIAN BECVAR, SILVIA LEITGEB, THOMAS PIEBER, EVA NOVAK, JULIA K. MADER, Graz, Austria

Background: Reimbursement and practitioner´s recommendations for the use of continuous subcutaneous insulin infusion (CSII) devices in type 2 diabetes (T2D) is restricted to a minority. Not only complexity of available systems but also concerns about efficacy and safety exist. Simple devices, which do not require programming and provide easy handling, might over-come these issues. Hereby we aimed to understand the knowledge and the attitude towards CSII of patients with T2D.

Material and Methods: A questionnaire survey in T2D was performed. It (21 questions) contained extractions from standardized questionnaires (bar-riers to insulin treatment, insulin treatment appraisal, problem areas in dia-betes) which focus on insulin therapy, diabetes treatment and quality of life aspects. For this analysis answers YES, rather YES, NO and rather NO were summarized to YES and NO.

Results: 100 patients (50 w, 50 w/o insulin therapy) participated.Patient characteristics: 29% female, mean age 63.3 y, diabetes duration

12.8 ± 9.1 y, A1c 57 ± 11 mmol/mol. While majority of subjects have never seen a CSII before and believes that it is more complicated than MDI treat-ment, about 70% of them believe that it might be helpful and more than 80% are confident, they could handle it (Figure).

Conclusion: Acceptance of CSII is high in patients with T2D. Clinical trials, testing easy-to-use devices will be needed to evaluate broader use in T2D.

Figure.

2384‑PUBIs a 4mm Insulin Pen Needle Best for All? An Independent Review of the LiteratureHENRIETTA E. MULNIER, HARIETT POPE, HAYA ABU GHAZALEH, London, United Kingdom

Recent International advice on insulin delivery advocates the use of a 4mm insulin pen needle for all. However, the evidence base is weak and potentially biased. Here we present an independent systematic critical review. A system-atic search of MEDLINE, EMBASE, and CINAHL was undertaken in November 2016. The search strategy combined three facets: diabetes mellitus, insulin pen needle, and adverse effects. Multiple terms were used to define each concept and only English-written articles published on or after 2006 were included in the screening process. Free-text searches were also performed. The search extracted 2,382 citations. Sixteen articles were included in the literature synthesis; 11 trials and five observational studies. Of the identified papers 12 (75%) were funded by insulin pen manufacturing companies. Criti-cal appraisal scores were mostly low to very low, with serious risk of bias such as lack of blinding, no power calculation, or influence of study design particularly in the use of scoring measures. Shorter needles were in general reported as preferred, though a large proportion of patients also stated no preference or preferred the longer needle. One of the ten studies that mea-sured pain reported less pain with a 6mm needle compared to a 5mm, and two further studies reported no difference in pain scores for 5mm compared to 8mm needles. One paper reported less pain using larger volumes and an 8mm needle than with a 6mm. Bleeding leakage and bruising scored similarly

for all the needle lengths; though these data were weak. Shorter needles in lean patients were associated with a low risk of intramuscular injection. Much inference has been made from this biased research. With better study design the literature may suggest that patients prefer any needle length from 4 to 8mm. It may be that short needles should be advocated in lean people; however, as the majority of insulin users are obese a more patient centred approach would be to offer a selection of needle lengths.

2385‑PUBMedtronic SmartGuard™ Technology Results in Positive Psycho‑logical Well‑Being in People Living with DiabetesSHWETA GOPALAKRISHNAN, JOHN MUECKLER, JOHN SHIN, Northridge, CA

Background: Patient-reported outcome on the impact of therapy on quality of life (QoL) is an important measure of successful diabetes management. Several aspects of psychological well-being of patients using the MiniMed® 530G system with SmartGuard technology (Threshold Suspend-TS) were evaluated.

Methods: From June 2016 to November 2016, responses were collected from TS users (n=406, ages 18-65 years) completing the (Bradley) Well-being questionnaire, 3-4 months after beginning MM530G therapy. Users included former MDI users (n=113), upgrade pumpers (n=267), and competi-tive switchers (n=26). The questionnaire measures psychological well-being in people with chronic illnesses and has been recommended by the World Health Organization for widespread use to evaluate impact of treatment and overall patient health. It measures positive and negative well-being on a 4-point scale (0-3, Not at all to All the time).

Results: The Table shows percent of TS users responding to the survey as experiencing minimal to no psychological issues. For the most part, more than 60% of patients showed positive well-being responses and less than 20% had responses showing negative well-being 3-4 months after begin-ning MM 530G therapy.

Table.

Supported By: Medtronic


2386‑PUBTitratable Fixed‑Ratio vs. Sequential Combination of Insulin Glargine and Lixisenatide: Propensity Score‑Matched Analysis to Compare LixiLan‑L and GetGoal Duo‑2 TrialsJURIS J. MEIER, JOSEP VIDAL, MINZHI LIU, RICCARDO PERFETTI, JULIO ROSEN-STOCK, Bochum, Germany, Barcelona, Spain, Somerset, NJ, Bridgewater, NJ, Dallas, TX

Treatment of T2DM uncontrolled on basal insulin glargine (iGlar) may be advanced with lixisenatide (Lixi) as a separate injection or switched to a titratable fixed-ratio combination with Lixi (iGlarLixi). These approaches were indirectly compared by propensity score-matching according to base-line covariates to minimize confounding; in long-standing iGlar-treated uncontrolled T2DM, simultaneous administration with iGlarLixi in the Lixi-Lan-L trial (n=367) was compared with sequentially adding Lixi in GetGoal Duo-2 (n=298). In 241 well-matched pairs comprising ~80% of participants, iGlarLixi provided significantly greater reductions in HbA1c, higher propor-tions of patients attaining HbA1c <7%, and greater decreases in PPG excur-sions (Table). Despite lower HbA1c with iGlarLixi, the incidence of hypoglyce-mia was similar between groups. Rates of GI AEs were lower with iGlarLixi

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vs. sequential addition of Lixi, likely due to slower up titration with iGlarLixi. Administration of iGlarLixi may have an intrinsic complementary mechanism of action controlling simultaneously both PPG and FPG in a more physi-ological way. This indirect comparison suggests that in basal insulin-treated T2DM in need of insulin intensification, iGlarLixi may offer an advantage over combining insulin and a GLP-1 RA in two separate injections.


2387‑PUBEffects of Incretins in People with Type 2 Diabetes on CSIIRUDOLF CHLUP, JANA ZAPLETALOVA, TZU HSUAN CHENG, ZDENEK RAMIK, MONIKA SLEZAKOVA, HANA ZALESAKOVA, Olomouc, Czech Republic, Paseka, Czech Republic

Metabolic control improvements resulting from Continuous Subcutaneous Insulin Infusion (CSII) in insulin + metformin (M) treated people with type 2 diabetes (PWD2) are often not sufficient to achieve optimal state. The pur-pose of this prospective pilot study was to assess the effect of incretins (liraglutide 1.2 mg/d or exenatide QW 2 mg) added to M (3 g/d) + CSII (insulin aspart) therapy. Fourteen PWD2 (8 men) on CSII + M, without serious com-plications, age 52.7 (34.3-68.8) y, diabetes duration 16.5 (5.0-20.3) y, BMI 36.6 (31.6-57.6) kg/m2, were monitored at 4 visits: 1) before CSII, 2) on CSII + M, 3) on CSII + M before incretin start, 4) on CSII + M + incretin after 3.1 (2.5-7.1) months. Medians (minimum-maximum), Wilcoxon Signed-Rank test and Bonferroni correction were applied to assess insulin/d (INS), evolution of HbA1c, mean plasma glucose of a daily 10-point glycemic profile (MPG), body mass (BM) Table 1. Correlation r (Spearman) between the change of respec-tive parameter at visit 4, 3, 2 vs. visit 1 and at visit 4 vs. visit 3 was sought for. P < 0.05 was considered significant. CSII appeared to enable reduction of INS with no increase of HbA1c/MPG. Incretins added to CSII + M resulted in significant reduction of both the HbA1c and BM. Correlation was revealed

between the change of INS and change of BM at visit 4 vs. visit 1 (r = 0.582, P = 0.029) and also at visit 3 vs. visit 1 (r = 0.574, P = 0.032). So, incretins may be considered as an effective addition to CSII + M treated PWD2.

Table 1. Diabetes Control at Visit 1-4. N=14; Median, Min-Max; P <0.05.Visit 1 before CSII 2 CSII+M 3 CSII+M 4 CSII+M

+incretin2 vs. 1 P 4 vs. 1 P 4 vs. 3 P

Insulin IU/d 85 38‑122

60 36.7‑77

77.3 61-112

64.3 47-98

0.022 NS NS

HbA1c mmol/mol 80 65-91

78 52-118

79 66‑117

63 51‑109

NS NS 0.008

MPG mmol/l 11.4 8.8‑14.5

10.3 8-12.7

9.4 6.7‑12.7

7.7 5.5‑12.2

NS 0.008 0.004

Body Mass kg 110.8 89-147.5

108.7 87.9-145.4

111.6 91.8‑144.4

109.6 90.6‑143.5

NS NS 0.008

2388‑PUBDulaglutide Treatment Reduces Glycemic Excursions in People with Type 2 Diabetes: A Post‑hoc Analysis of Six Phase 3 Random‑ized Clinical TrialsGUILLAUME CHARPENTIER, LUIS E. GARCÍA-PÉREZ, VIVIAN T. THIEU, NAN JIA, JENNIE G. JACOBSON, VALERIA PECHTNER, Evry, France, Indianapolis, IN, Paris, France

The once-weekly GLP-1 receptor agonist dulaglutide (DU) demonstrated a significant A1c reduction and the potential for weight loss in adults with uncontrolled type 2 diabetes (T2D) in the AWARD phase 3 clinical program. DU has also demonstrated significant reductions in fasting, pre- and post-prandial glucose levels. To further understand the glycemic effects of DU 1.5 mg and 0.75 mg, we performed a post-hoc analysis examining glycemic excursions (morning, midday, evening, and daily mean) obtained by self-monitored blood glucose testing at 6 or 12 month time points. Analysis was performed by individual study (AWARD-1, -2, -3, -6, -8 and -9), given the different background therapies. Glycemic excursions were derived by sub-tracting blood glucose values before each meal from blood glucose values 2 hours after the meal. Treatment with DU 1.5 mg resulted in significant reduc-tions from baseline in daily mean glucose excursions (change: -7 to -15 mg/dL, p<0.05) in all six trials. The effect of DU 1.5 mg on glycemic excursions was most evident in the morning followed by the evening (Table). The trend of the glycemic excursion reductions from baseline with DU 1.5 mg and DU 0.75 mg were similar. The effect of DU treatment on glycemic excursions may contribute to overall improvements in glycemic control in patients with T2D treated with DU.

Table.

Supported By: Eli Lilly and Company

2389‑PUBSimultaneous vs. Sequential Combination of Insulin Glargine and Lixisenatide: Propensity Score‑Matched Analysis to Compare Lixi‑Lan‑O and GetGoal Duo‑1 TrialsJULIO ROSENSTOCK, F. JAVIER AMPUDIA-BLASCO, FRANCESCO GIORGINO, MINZHI LIU, RICCARDO PERFETTI, YEHUDA HANDELSMAN, Dallas, TX, Valencia, Spain, Bari, Italy, Somerset, NJ, Bridgewater, NJ, Tarzana, CA

Simultaneous treatment with insulin glargine (iGlar) + lixisenatide (Lixi) as a titratable, fixed-ratio combination (iGlarLixi) is a new treatment option vs. sequential administration of each component in T2DM uncontrolled on metformin ± other oral antidiabetic drugs (OADs). Propensity score matching based on baseline covariates to minimize confounding factors was used to indirectly compare simultaneous administration with iGlarLixi in LixiLan-O

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(n=469) vs. sequential initial iGlar therapy for 12 weeks, followed by addition of Lixi if iGlar was insufficient, in GetGoal Duo-1 (n=223). iGlarLixi showed significantly greater reductions in HbA1c despite lower insulin doses, greater proportions of patients reaching HbA1c <7%, and greater decreases in 2-h PPG, FPG, and weight vs. sequential administration of iGlar and Lixi in 87 matched pairs (Table). Rate of hypoglycemia was lower with iGlarLixi vs. sequential treatment, likely due to the lower insulin dose. iGlarLixi showed better GI tolerability, possibly due to slower Lixi titration.

In conclusion, this indirect comparison suggests that early treatment with a simultaneous combination of basal insulin and GLP-1 RA may be more effective and have better GI tolerability vs. a sequential approach of add-ing a GLP-1 RA when basal insulin therapy needs to be advanced in T2DM uncontrolled on OADs.


2390‑PUBPharmacodynamics, Pharmacokinetics, Safety, and Tolerability of the Novel Dual GIP/GLP‑1 Agonist (RG7697) after Single Subcutane‑ous Administration in Healthy SubjectsAGNÈS PORTRON, SHIRIN JADIDI, NEENA SARKAR, RICHARD DIMARCHI, CHRISTOPHE SCHMITT, Basel, Switzerland, New York, NY, Indianapolis, IN

RG7697 (NNC0090-2746), a novel dual GIP/GLP-1 agonist for the treat-ment of type 2 diabetes mellitus (T2D), was administered in an ascending single-dose study as s.c. injection to evaluate safety, PK, and PD. Clinical-Trials.gov; NCT01676584. A total of 51 healthy volunteers were enrolled in this double-blind, placebo-controlled study and randomized to receive either active drug (n=6) or placebo (n=2) in one of 7 dose cohorts (0.03-5 mg). Adverse events were monitored and drug concentration, fasting gly-cemic parameters, vital signs, ECG, antibody formation and routine labora-tory parameters were measured over 72 hours post-dose. A meal tolerance

test (MTT) was performed at the same time on day -1 (baseline) and day 1. RG7697 was safe and generally well tolerated in healthy subjects follow-ing s.c. injections up to 3.6 mg. Tolerability was limited by gastrointestinal-related adverse events (nausea and vomiting) at the highest dose tested (5 mg). RG7697 was associated with a mild increase in heart rate but did not provoke hypoglycemia. RG7697 plasma concentration peaked at 2 to 6 hours post-dose and exhibited biphasic elimination with apparent terminal half-life in the range of 19.3 to 25.4 h. Exposure (AUC) increased with dose in a manner slightly greater than dose-proportionally. RG7697 had no effect on fasting glycemic parameters in normoglycemic volunteers. However, during MTT and at doses ≥1.8 mg, it reduced the glucose Cmax (-46.2%) and delayed glucose tmax without affecting overall exposure to glucose. RG7697 effect on insulin was more pronounced with reduction of both insulin Cmax (-64.2%) and AUC (-50.8%). Single s.c. injections of RG7697 up to 3.6 mg were gener-ally well tolerated. Evidence of antidiabetic effect and pharmacokinetic pro-files consistent with once-daily dosing made the drug suitable to be further tested in multiple-dose clinical trials in T2D patients.

Supported By: F. Hoffmann-La Roche AG; Novo Nordisk A/S

2391‑PUBThe Association between iGlarLixi and Patient Satisfaction with Their Treatment’s Ability to Control Type 2 Diabetes (T2D) Is Medi‑ated by Reduced Glycemic Variability (GV)BORIS KOVATCHEV, AUDE ROBOREL DE CLIMENS, TERRY DEX, MICHELLE ROB-ERTS, LING YANG, MINZHI LIU, LINDA GONDER-FREDERICK, Charlottesville, VA, Lyon, France, Bridgewater, NJ, Somerset, NJ

The aim of this post-hoc analysis was to evaluate the association between iGlarLixi, GV, and patients’ (pts’) satisfaction with their treatment’s ability to control their diabetes (measured by the Diabetes Management [DM] score of Treatment-Related Impact Measure for Diabetes [TRIM-D].)

LixiLan-L is a phase 3, 30-week RCT in pts with T2D previously on basal insulin ± OADs treated with insulin glargine 100 units/mL (iGlar) or iGlar-Lixi, a fixed-ratio combination of iGlar and the GLP-1 RA lixisenatide. The DM domain of TRIM-D contains questions on pts’ satisfaction with diabe-tes treatment effects. DM scores were recorded at baseline and week 30, together with 7-point self-measured plasma glucose (SMPG) profiles used to calculate several GV metrics. A DM score increase ≥ 8.2 is a clinically meaningful difference; pts with DM increase ≥ 8.2 were considered DM responders.

At week 30, 39.3% of iGlarLixi vs. 32.6% of iGlar-treated pts were DM responders (P = 0.0577). Among DM responders, iGlarLixi (vs. iGlar) resulted in significantly greater reductions in mean amplitude of glucose excursions (24% vs. 5%; P < 0.0001) and area under the SMPG curve (19.1% vs. 5.6%; P < 0.0001) indicating reduced GV. Most prominent was the reduction in the magnitude of postprandial SMPG excursions (measured by the High Blood Glucose Index [HBGI]) 56% for iGlarLixi vs. 17% for iGlar, P < 0.0001. HGBI reduction was correlated with a greater change in DM score, particularly for iGlarLixi vs. iGlar (r = −0.30; P = 0.0019 vs. r = −0.19; P = 0.0822).

In pts with T2D, iGlarLixi reduces GV more than iGlar alone (published data). We conclude that this differential effect is preserved in the subpopu-lation of pts who reported more satisfaction with their treatment’s ability to control their diabetes; this subpopulation is larger with iGlarLixi, and the self-reported effect of treatment is correlated with a reduction in the mag-nitude of postprandial glucose excursions.

Supported By: Sanofi U.S.

2392‑PUBImprovement of β‑Cell Function and Cardiovascular System in Patients with Newly Diagnosed T2DM after Long‑Term GLP‑1R Ago‑nist TreatmentYANJUN WANG, YAN CHEN, JIAXIN WANG, SHUJIE ZHAO, CHUAN ZHANG, Changchun, China

Objective: To observe the effect of GLP-1 receptor agonist Exenatide treatment in β-cell function and the cardiovascular system in patients with type 2 diabetes mellitus.

Methods: 183 patients were newly diagnosed with type 2 diabetes mel-litus, after treatment with continuous subcutaneous insulin infusion for 2-3 weeks, on the basis of diet and exercise, continue to Exenatide (5μg, twice a day) subcutaneous injection. Follow-ups were conducted on the 183 patients before and after treatment 1, 3, 6,12 and 24 months, measured the fasting plasma glucose (FPG), 2h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), waist circumference, weight, body mass index (BMI), Systolic blood pressure (SBP), Diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low

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density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), 2h postprandial insulin (INS120). Calculated insulin sensitive index (HOMA-IS) and the index of insulin resistance (HOMA-IR) by steady-state model assessment (HOMA).

Results: All time points after treatment compared with before treatment, the changes of SBP, DBP, TG, TC, HDL-C, LDL-C, FINS, INS120, HOMA-IS, HOMA-IR were in statistically significant (P<0.05), changes in the levels of treatment efficacy indicators were significant at the 3-month follow-up (p < 0.001); however, the levels of each indicator stabilized by the 6-month follow-up, there was no statistical difference (p > 0.05).

Conclusion: Treatment with GLP-1R agonists could significantly improve β-cell function and lower blood pressure, decreases the level of blood-lipid, protect cardiovascular system in patients with newly diagnosed type 2 diabetes.

2393‑PUBThe Effects of Dulaglutide and Omarigliptin: A Crossover Trial Assessed by Two‑Week Continuous Glucose Monitoring and Treat‑ment Satisfaction SurveyTAKAHIRO TOSAKI, HIDEKI KAMIYA, TAKAMI KATAYAMA, AKEMI INAGAKI, MASAKI KONDO, ERIKO NAGAO, YUICHIRO YAMADA, YOSHIRO KATO, SHIN TSUNEKAWA, TATSUHITO HIMENO, SHIORI SATO, YUKI NAKAYA, JIRO NAKA-MURA, Nagoya, Japan, Nagakute, Japan

The efficacy of dulaglutide (DU) and omarigliptin (OM) has only been reported through clinical trials, and the differences between these agents under the general practice, including CGM data, are yet to be clarified. This study was conducted to compare the efficacy and treatment satisfaction (DTSQ) of DU and OM in diabetic patients. Randomization to either group A or B followed after 4 wk observation (O) without drug intervention. Group A; OM 25mg for 5 wk, no OM for 4 wk, DU 0.75mg for 5 wk, and no DU for 1 wk. Group B; the same pattern with OM and DU switched. In both groups, the analyses of CGM were conducted during the last 7 days of O and the last 14 days of OM or DU treatment. DTSQ was conducted and HbA1c, GA, insulin, and C-peptide were measured in wk 4 of O and 4 wk after treatment with each agent. (UMIN R000025287) The interim report includes 7 registered subjects with 4 completions. The average glucose level was 177.8 mg/dl dur-ing O, unchanged with OM (5th wk: 176.0 mg/dl, 6th wk: 185.8 mg/dl), and decreased with DU (5th wk: 148.0 mg/dl, 6th wk: 159.5 mg/dl). The variability of glucose levels was unchanged with OM and reduced with DU. Duration with glucose levels over 140 mg/dl in 24 hrs improved from 18.7 hrs during O to 16.6 and 17.3 by OM, and 13.0 and 14.5 by DU. The total score of DTSQ pri-mary factors was increased from 26.3 during O to 29.5 by OM and to 27.0 by DU. These observations suggest that glucose lowering effects of DU would be stronger than those of OM, and that better treatment satisfaction could be obtained by OM and DU.

2394‑PUBThe Effect of Liraglutide on Oxidative Nucleic Acid Modifications in Women with Prior Gestational Diabetes MellitusEMIL L. LARSEN, SIGNE FOGHSGAARD, LOUISE VEDTOFTE, ELISABETH R. MATHIESEN, PETER DAMM, JENS A. SVARE, TINE D. CLAUSEN, TRINE HEN-RIKSEN, HENRIK E. POULSEN, FILIP K. KNOP, TINA VILSBØLL, Hellerup, Denmark, Copenhagen, Denmark, Herlev, Denmark, Hillerød, Denmark

Ribonucleic acid (RNA) oxidation, measured by urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with mortality in patients with type 2 diabetes. Animal studies have shown that liraglutide, a gluca-gon-like peptide-1 analog, lowers oxidative modifications. Here, we inves-tigated the effect of liraglutide on oxidative nucleic acid modifications in women with prior gestational diabetes mellitus (pGDM). Women with pGDM (n=104) were randomized to one-year double-blinded intervention with lira-glutide (1.8 mg, once-daily) (n=49) or placebo (n=55) followed by one-year open-label intervention. An age and BMI matched control group of healthy women without pGDM was also studied (n=15) at baseline. The urinary excretion of 8-oxoGuo and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) was determined at baseline, after 53 weeks (52 weeks intervention fol-lowed by a one-week wash-out), and after 104 weeks by ultra-performance liquid chromatography tandem mass-spectrometry as a measurement of whole body RNA and deoxyribonucleic acid (DNA) oxidation, respectively. At baseline, similar urinary excretion of 8-oxoGuo/creatinine (P=0.86) and 8-oxodG/creatinine (P=0.39) were seen in women with and without pGDM. Treatment with liraglutide for 52 weeks did not affect urinary excretion of 8-oxoGuo/creatinine (delta values (mean±SD): -0.01±0.36 vs. -0.00±0.52 nmol/nmol, P=0.91) or 8-oxodG/creatinine (-0.01±0.25 vs. 0.08±0.45 nmol/nmol, P=0.31) vs. placebo treatment. The one-year open-label extension with liraglutide did not affect urinary excretion of 8-oxoGuo/creatinine

(delta values from baseline (mean±SD): 0.05±0.29 vs. 0.13±0.43 nmol/nmol, P=0.45) or 8-oxodG/creatinine (0.15±0.25 vs. 0.30±0.33 nmol/nmol, P=0.10) vs. no treatment.

In conclusion, women with and without pGDM exhibit similar RNA and DNA oxidation, and liraglutide treatment for two years does not seem to affect RNA and DNA oxidation in women with pGDM.

Supported By: Novo Nordisk A/S; Novo Nordisk Foundation; AP Møller Founda-tion; Danielsens Foundation

2395‑PUBA Novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP‑089, Induces Weight Loss through a Reduction In Fat, albeit Not Lean Mass, while Improving Food PreferenceSOFIE GYDESEN, SARA T. HJULER, ZENIA FREVING, KIM VIETZ ANDREASSEN, NINA SONNE, MORTEN ASSER KARSDAL, KIM HENRIKSEN, Herlev, Denmark

Obesity and associated co-morbidities, such as type 2 diabetes and nonal-coholic fatty liver disease, are major health challenges - hence, development of weight loss therapies with the ability to reduce the co-morbidities is key. The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated. Further, we eluci-date weight-independent effects of KBP-089 using a weight-matched group. High fat diet fed rats were treated with KBP-089 s.c., at 0.625, 1.25, 2.5 μg/kg and vehicle resulting in a dose-dependent and sustained ~17% weight loss by the 2.5 μg/kg. Moreover, KBP-089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP-089 improved glucose homeostasis through improved insulin action. To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight-matching led to improved glucose homeo-stasis through lowered plasma insulin; however, these were inferior to the effect of KBP-089. In the food preference test, normal diet rats obtained 74% of their calories from chocolate. KBP-089 administration reduced total caloric intake, and induced a relative increase in chow consumption while drastically lowering the chocolate compared to vehicle. The novel DACRA, KBP-089 induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet-induced weight loss.

2396‑PUBThe Novel DACRA, KBP‑089, Lowers Body Weight and AST Levels in High‑Fat, High‑Cholesterol Fed RatsSOFIE GYDESEN, MORTEN ASSER KARSDAL, KIM HENRIKSEN, Herlev, Denmark

Obesity and associated morbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD) are among the greatest health chal-lenges, hence there is an urgent need for treatments, which substantially reduce body weight, and improve glucose control and liver health. In this study, we evaluate the effect of KBP-089 - a highly potent dual amylin- and calcitonin receptor agonist (DACRA) - on body weight, glucose control, and AST and ALT levels in rats fed a high fat, high cholesterol and cholate diet (65%, 2% and 0.5%, respectively) (HFCC). 6 week old rats received high fat diet (HFD) for 8 weeks followed by HFCC for another 8 weeks. After HFD, the rats were assigned into experimental groups according to body weight and four-step dose escalated (0.625, 1.25, 2.5 and 5.0 μg/kg, s.c., s.i.d.) once weekly followed by 4 weeks of treatment with either dose. Dose escalation induced minimal and transient reduction in food intake at every escalation step, and the following treatment with 1.25, 2.5 and 5 μg/kg resulted in a significant ~ 8%, 16% and 17% vehicle-corrected weight loss, respectively, with a corresponding reduction in fat depots. KBP-089 treatment also led to a reduction of the HFCC induced increase in liver weight (2.5 μg/kg, p<0.05; 5 μg/kg, p<0.01) and a significantly reduced circulation AST (1.25 μg/kg, p<0.05; 2.5 μg/kg, p<0.05 and 5 μg/kg, p<0.01), albeit no difference was observed in ALT levels. Finally, all treatment groups showed a trend towards lower blood glucose levels compared to vehicle during OGTT, and interest-ingly, KBP-089 groups dose-dependently suppressed the glucose-induced insulin hypersecretion observed in vehicle during OGTT (1.25 μg/kg, p<0.05; 2.5 μg/kg, p<0.001 and 5 μg/kg, p<0.001).

In conclusion, KBP-089 induced and sustained a significant weight loss, reduced overall adiposity, and lowered AST levels. In addition, KBP-089 improved glucose tolerance, hence underscoring the potential of KBP-089 in obesity and related morbidities as T2D and NAFLD.

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2397‑PUB

2398‑PUBChronic, but Not Acute, Incretin Therapy Reduces Postprandial Free Fatty Acid Levels in Prediabetic IndividualsABSALON D. GUTIERREZ, JR., KARLA BERMUDEZ SAINT ANDRE, VALA HAMIDI, KAYLA RIGGS, SARA COVERDALE, AMY DURSTELER, NITYA KUMAR, HIBA ALI, VISHNU MOHAN, HEINRICH TAEGTMEYER, Houston, TX

GLP-1 receptor agonists and DPP-4 inhibitors exert an acute anti-inflam-matory effect in the fasting state of type 2 diabetes mellitus (T2DM). It is less established whether the same effects are observed in the postprandial state of prediabetic humans. Sixteen adult prediabetic subjects (age 50 ± 2 years, BMI 32.5 ± 0.4 kg/m2, HbA1c 5.96 ± 0.05%) participated in a single center, randomized, crossover, placebo-controlled double-blinded prospec-tive trial utilizing the following medications: exenatide, saxagliptin, and placebo. Fasting patients presented to the Clinical Research Unit. Baseline venous blood was drawn and a single dose of study medication adminis-tered. Next, subjects ate a standardized high-fat test meal, and venous blood samples were collected every 2 hours for a total of 6 hours. Blood was analyzed for markers of free fatty acids (FFAs), insulin, glucose, and C-reactive protein (CRP). These procedures were repeated for the remaining study arms. Subsequently, seven of these subjects participated in an open-label extension study. Exenatide extended-release (ER) was administered for six weeks, after which the above procedures were repeated. A single dose of exenatide led to a smaller reduction of postprandial FFAs compared to saxagliptin and placebo. Postprandial insulin and glucose levels were lower with single-dose exenatide, compared to saxagliptin and placebo. Six weeks of exenatide ER, compared to single dose exenatide, showed greater reductions of postprandial levels free fatty acids, as well as increased post-prandial insulin and no decrease in postprandial glucose. Baseline fasting glucose levels decreased. There were no changes in CRP levels These data show that six weeks of exenatide ER significant reduced postprandial free fatty acid levels, and effect which was not seen in acute exenatide admin-istration.

Supported By: National Institutes of Health (UL1TR000371); National Center for Advancing Translational Sciences (KL2TR000370)

2399‑PUBDual Amylin and Calcitonin Receptors Agonists (DACRA) Activate Overlapping Metabolic Signaling Pathways in Muscle and Adipose TissueANNA T. LARSEN, SOFIE GYDESEN, KIM V. ANDREASSEN, MORTEN KARSDAL, KIM HENRIKSEN, Herlev, Denmark

Dual amylin and calcitonin receptor agonists (DACRA) are novel candi-dates for treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, blood glucose and insulin sensitivity. KBP-042 is a DACRA with these beneficial effects, however it is unclear how KBP-042 mediates the improvements in metabolic status, and to what extent it involves the amylin or the calcitonin receptor.

Here we searched to identify the target tissues to elucidate the effect of DACRAs directly in the tissue by evaluation of signaling pathway activation. KBP-042 mediated tissue activation was studied in vivo in Sprague Dawley rats treated with a single subcutaneous dose of the DACRA KBP-042 (5 μg/kg) followed by collection and extraction of tissue involved in metabolism and analysis of activated signaling pathways (Erk; Akt; STAT3) by Western blot.

Administration of KBP-042 (5 μg/kg) acutely activated Akt signaling in both muscle and epididymal adipose tissue in vivo. We did not observe any differences in Erk and STAT3 signaling activation in muscle and adipose tis-sue from rats treated with KBP-042. Furthermore, no pronounced changes in Akt, Erk and STAT3 phosphorylation were observed in other tested target tissue (liver; kidney; pancreas).

In conclusion, the DACRA KBP-042 acutely activates Akt signaling in mus-cle and epididymal adipose tissue, indicating the beneficial metabolic effect of KBP-042 directly in the metabolic tissue. Further analysis including admin-istration of rat amylin or rat calcitonin will benefit to evaluate whether the improvements in metabolic status and observed tissue specific kinase acti-vation are mediated by activation of the amylin or the calcitonin receptor.

2400‑PUBEffect of GLP‑1 Analogues on Free Fatty AcidKENTARO SAKAMOTO, SUMIE OKAHATA, TAKAKO MITSUMATSU, TERUO SHIBA, Tokyo, Japan

Purpose: To evaluate the effect of GLP-1 receptor agonists and elucidate the mechanisms through which to reduce glucose on the focus of free fatty acids.

Methods: We performed mixed meal tests (MMT) for patients initiating GLP-1 receptor agonists (lixisenatide or liraglutide) use before and after 3 days (3 d), and/or 1 month (1M) administration. We checked plasma glucose (PG), insulin (IRI), CPR, glucagon (IRG), and free fatty acids (FFA).

Results: 51 patients (37 men and 14 women; mean age 53.6 years and HbA1c 9.74±1.84%) were analyzed. The breakdown of GLP-1 receptor ago-nists was 26 of lixisenatide, and 25 of liraglutide. All patients underwent MMT was performed for all patients at baseline, 48 of them underwent MMT at 3 d, and 18 at 1M. The baseline mean glucose value was (127, 142, 170, 204, 203, 177) at (0, 15, 30, 60, 120, 180) minutes, respectively. It changed to (121, 129, 145, 157, 142, 131) on 3 d, and (132, 140, 151, 170, 136, 126) after 1M. Whereas fasting PG values showed no significant reduction, PG at 15 min reduced on 3 d, and PGs at 30, 60, 120, and 180 min reduced after 3 d and 1M. IRI showed significant reduction at 120 and 180 min on 3 d, and increase at fasting after 1M. CPR increased at 0, 15 min and reduced at 180 min on 3 d. IRG reduced at 30, 60, and 120 min on 3 d and increased at 0, 15, and 180 min after 1M. FFA increased at 180 min on 3 d, and reduced significantly at 0, 15, and 30 min after 1M.

2401‑PUBThe Dual Amylin‑ and Calcitonin‑Receptor Agonist KBP‑042 Reduces Food Intake by Activating Amlin ReceptorsSARA T. HJULER, Herlev, Denmark

KBP-042 is a potent peptide activator of the amylin and calcitonin recep-tors. In in vitro studies, KBP-042 activates both the calcitonin receptor and the amylin receptor effectively. Furthermore, KBP-042 activates both recep-tors at a lower dose compared to the native ligands. In this study, we tested 3 different doses of calcitonin and amylin against low dose of KBP-042 in obese Sprague-Dawley rats. 6 weeks old Sprague-Dawley rats fed a high fat-diet (HFD) for ten weeks, were stratified into groups according to body weight. Study 1: Vehicle, rat Amylin 5, 50 or 500 μg/kg, rat Calcitonin 5, 50 or 500 μg/kg and KBP-042 (5 μg/kg). The rats were dosed s.c. with drug or saline and food intake and body weight were monitored. Study 2: Vehicle, rat Amylin 50 μg/kg/day, rat Calcitonin 50 μg/kg/day, KBP-042 5 μg/kg/day. All animals received subcutaneous continuous infusion (Alzet osmotic mini-

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pump) of either saline or drug for 21 days. Food intake and body weight were monitored. Administration of 5 μg/kg KBP-042 strongly reduced acute food intake both after 4 hours (59%, p<0.001) and up to 24 hours (30%, p<0.001). Reduction of food intake after 4 hours was only reduced with 500 μg/kg rat calcitonin (39%, p<0.001), 50 μg/kg rat amylin (40%, p<0.001) and 500 μg/kg rat amylin (46%, p<0.001). Similarly, in the chronic study only amylin managed to suppress food intake significantly (34%, p<0.05 after 3 days) whereas the food intake was unchanged using rat calcitonin. KBP-042 did however, have a strong effect on food intake (56%, p<0.01) and conse-quently led to a reduction in body weight (6%, p<0.05). KBP-042 efficiently reduced body weight and improved glucose tolerance. Similar effects were achieved using high doses of amylin, while the effect of rat calcitonin on obese rats was uncertain. These findings indicate that the primary effects of KBP-042 is mediated through activation of amylin receptors, however higher doses and mixtures of calcitonin and amylin needs to be explored.

2402‑PUBThe Effects of Acute and Chronic Incretin Therapy on Endothelial Function in Humans with PrediabetesABSALON D. GUTIERREZ, JR., VALA HAMIDI, KARLA BERMUDEZ SAINT ANDRE, SARA COVERDALE, KAYLA RIGGS, AMY DURSTELER, HIBA ALI, VISHNU MOHAN, NITYA KUMAR, HEINRICH TAEGTMEYER, Houston, TX

Studies show conflicting data regarding the effect in incretin thera-pies on endothelial function in insulin-resistant humans. We investigated the efficacy of acute and chronic incretin therapy on postprandial endo-thelial function and hypertriglyceridemia in prediabetic humans Fifteen adult prediabetic subjects (age 51 ± 2 years, BMI 32.5 ± 0.4 kg/m2, HbA1c 5.96 ± 0.05%) participated in a single center, randomized, crossover, pla-cebo-controlled double-blinded prospective trial utilizing the following med-ications: exenatide, saxagliptin, and placebo. For each study arm, fasting patients presented to the Clinical Research Unit. Forearm blood flow (FBF) was measured via strain gauge venous occlusion plethysmography. Blood was drawn for lipid levels. Study medication was given and subjects ate a standardized high-fat test meal. Blood was collected every 2 hours, and FBF was measured every three hours, for a total of 6 hours. These procedures were repeated for the remaining study arms. Subsequently, seven patients participated in an open-label extension study. Exenatide extended release (ER) was administered for six weeks, after which the above procedures were repeated. Single doses of exenatide and sitagliptin improved postprandial hypertriglyceridemia, but showed no significant changes in resting or peak postprandial FBF when compared to placebo. Six weeks of exenatide ER, compared to single dose exenatide, improved fasting resting but not peak FBF, but did not improve postprandial resting or peak FBF. The data show that chronic exenatide ER therapy led to mild improvements in fasting but not postprandial endothelial function in prediabetic humans, via FBF measure-ments. Acute exenatide and saxagliptin did not improve endothelial func-tion, though postprandial triglyceride levels were reduced with both drugs. Long-term administration of exenatide may offer cardiovascular protection beyond glucose control in prediabetes.

Supported By: National Institutes of Health (UL1TR000371); National Center for Advancing Translational Research (KL2TR000370)

2403‑PUBEfficacy and Safety of Exenatide Once Weekly in Italian Real PracticeOLGA E. DISOTEO, PAOLO ERPOLI, LAURA BARUFFALDI, ENRICA CHEBAT, MARIA E. MALIGHETTI, RAFFAELLA MANNA, PAOLO MARENCO, ANTONIO ROSSI, LAURA SALI, Milan, Italy, Gallarate, Italy, Cesano Boscone, Italy, Tradate, Italy, Garbagnate Milanese, Italy, Saronno, Italy

Exenatide once weekly, a glucagon-like peptide-1 receptor agonist, has shown to improve glycemic control and weight loss in type 2 diabetic patients. These positive effects in randomized clinical trials were lasting and there was no evidence of loss of these effects while exenatide once weekly treatment was continued. To evaluate if these effects are pres-ent also in our real practice we conducted a retrospective review of 218 type 2 diabetic patients (pts) started therapy with exenatide once weekly from March 2014 to June 2016 in our Diabetes Units. At the beginning of therapy all pts had HbA1c between 7,5% (58 mmol/mol) and 8,5% (69 mmol/mol) in accordance with refund indications of our National Health Service, age less than 50 years 45 pts (21%), 50-70 yrs 142 pts (65%), more than 70 yrs 31 pts (14%), BMI less than 25 Kg/m2 7 pts (3%), between 25-30Kg/m2 85 pts (39%), more than 30 Kg/m2 126 pts (58%), 140 pts (64%) were in dual therapy and 112 pts were female (51%). Our data demonstrated that exenatide once weekly decreases HbA1c less than 0,5% in 46 pts (21%), between 0,5% and

1% in 90 pts (41%) and more than 1% in 82 pts (38%) and weight less than 2 Kg in 45 pts (21%), between 2-3 Kg in 83 pts (38%) and more than 3 Kg in 90 pts (41%), mean treatment duration 14 months. The adverse events in site of injection were present for 28 pts (13%) and gastrointestinal disorders in 36 pts (17%), only few patients interrupted therapy for these side effects. Our results confirm efficacy and safety of exenatide once weekly in accord with literature data, although our population is older and with lower BMI compared the populations of the trials; the positive effects on HbA1c values and weight appear to be maintained over time but the relative short period of marketing in Italy of this drug cannot provide conclusive data. Our intention is to continue observation of these patients to increase information about durability of efficacy and drug tolerance in Italian real practice.


2404‑PUBThe Role of Dipeptidyl Peptidase‑4 Inhibitors in Fat Metabolism in Patients with Type 2 DiabetesALEXANDER S. AMETOV, ADUATE EDUCATION STUDIES GUSENBEKOVA D.G. RUSSIAN MEDICAL ACADEMY OF POSTGR, Moscow, Russian Federation

Objective: To evaluate the influence of combined therapy of sitagliptin and metformin on fat metabolism in patients with type 2 DM.

Materials and Methods: The study involved 82 patients with obesity, lipid metabolism disorders, who have not reached target levels HbA1s after met-formin and diet therapy. Gr 1 (n=42) received co-formulated drug, consisting of sitagliptin 100mg and metformin 2g twice a day. Gr 2 (n=40) received metformin 2 g/day. Dynamics of FG, PPG, HbA1c, weight, WC, lipid profile, insulin, proinsulin, leptin, adiponectin, HOMA IR, HOMA-β index was evalu-ated at baseline and at 6 months of therapy. MRI was performed to assess visc fat in all the patients.

Results: Patients in both gr demonstrated significant positive changes in the levels of FG, PPG, and HBA1c. Gr I HbA1c decreased from 8,3 to 6,6%, gr II from 8,35 to 7,62%. FPG and PPG in gr 1 were reduced by 2,67 and 3,26 mmol/l, and gr II by 0,33 and 0,64. Gr I weight loss was 4, 9 kg, gr II 2,0 kg. WC shortened by 6, 5 sm in gr I, gr II by 2,42 sm. MRI showed a significant reduction of visceral fat area by 20,6 sm2 in gr I, compared to gr II with 5, 7 sm2 reduction. Dynamics of the area of the subcutaneous fat there is no reliable dynamics between gr. No significant differences in the dynamics of TCh, HDL between the gr were found. Gr I IRI reduction was 3.45 mcU/ml, gr II 1.63 mcU/ml. Proinsulin level dropped down in gr I by 2, 93, in gr II by 1, 26, C-pept level increased by 1, 4 ng/ml, in gr II 0.16 ng/ml. HOMA β grew up in gr I by 23.4 SU, in gr II by 4.8 SU. Proinsulin/insulin ratio dropped down in gr I by 0, 19, in gr II by 0, 02. There were no significant differences between the groups in the dynamics of HOMA IR and both gr demonstrated positive dynamics. Adiponectin levels were different between the gr there was an increase by 1.9 ng/ml in gr I, in gr II by 0.49 ng/ml. Leptin lowered by 7.37 ng/ml in gr I, in gr II by 1.21 ng/ml.

Conclusion: Combined therapy sitagliptin and metformin received glyce-mic important and nonglikemic effects and noted improvement in function of B cells of the pancreas.

2405‑PUBIndependent Predictors for HbA1c Decline with Sitagliptin as a Third Line Oral Hypoglycemic Agent in Poorly Controlled Type 2 Diabetes Patients in a Singapore Primary Care SettingPOH CHING TAN, WEI LIANG DAVID NG, KHAI WEI TAN, YONGTAI GARETH YEO, YILIN JIANG, Singapore, Singapore

Background: There is uncertainty whether dipeptidyl peptidase-4 inhibi-tors (e.g., sitagliptin) are equally effective in different groups of patients with poorly controlled type 2 diabetes on two oral hypoglycemic agents. Our study aimed to quantify the improvement in HbA1c when sitagliptin was started as a third line agent at varying HbA1c levels, and to identify the independent predictors of sitagliptin efficacy in these patients.

Method: The clinical records of type 2 diabetes patients on maximal doses of metformin and glipizide, and newly started on sitagliptin with baseline HbA1c between 7 to 8.9% were retrospectively compared with a matched cohort of patients with baseline HbA1c ≥ 9%. The primary outcome was the change in HbA1c (Δ HbA1c) after 6 months of adding sitagliptin as a third line agent. Independent predictors of greater HbA1c reduction were identified using univariate and multivariate analysis.

Results: 327 patients were included in the study. Δ HbA1c in higher base-line HbA1c patients (≥9%) was significantly greater than the lower base-

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line HbA1c (7- 8.9%) patients (1.10 vs. 0.60; p<0.001). Patients who were acarbose-naïve before sitagliptin initiation had a greater Δ HbA1c, as com-pared to those who had used acarbose at baseline (0.90 vs. 0.50; p< 0.001). Multivariate analysis showed that independent predictors of greater HbA1c improvement after adjusting for potential confounders were higher baseline HbA1c, older age and being acarbose-naïve. There was no significant differ-ence in HbA1c reduction between patients on sitagliptin 50mg and 100mg (0.80 vs. 0.80; p= 0.546).

Conclusion: Our analysis showed that sitagliptin, as a third line hypoglyce-mic agent showed significant glycemic improvement in patients with higher baseline HbA1c, older age and being acarbose-naïve. Analysis of a larger popu-lation over an extended period of time is warranted to confirm these findings.

2406‑PUBBaseline HbA1c Level Correlates with Vildagliptin’s Efficacy for T2DM Treatment: A Subgroup Analysis of VISION StudyLI NONG JI, LING LI ZHOU, CHANG YU PAN, JU MING LU, LE WANG, BIN HUI WANG, JAMES HE, Beijing, China, Shanghai, China

Correlation between baseline HbA1c and efficacy of Chinese patients with T2DM was assessed using data from the fully published VISION study (ClinicalTrials.gov: NCT01541956). The post-hoc retrospective analysis of the VISION data was conducted on the full analysis set (FAS) population with last observation carried forward (LOCF). Patients receiving Vildagliptin plus low dose metformin (VLDM) and high-dose metformin (HDM) groups were fur-therly grouped into 3 tertiles/subgroups based on their baseline HbA1c levels: “HbA1c ≤ 6.7%” (1st tertile), “6.7 <HbA1c ≤ 7.4%” (2nd tertile) and “HbA1c >7.4%” (3rd tertile). HbA1c changes from baseline (ΔHbA1c) at weeks 12 and 24 were assessed in all subgroups. Our results confirmed the higher baseline HbA1c can get more HbA1c reduction in both treatment groups. In VLDM group, baseline HbA1c >7.4% was associated with significantly greater HbA1c reduction vs. HDM both at week 12 (ΔHbA1c= -0.87± 0.97% vs. -0.53± 1.15%, P=0.001) and at week 24 (ΔHbA1c= -0.91± 1.11% vs. -0.66± 1.05%, P=0.0127). While patients in other two tertiles receiving VLDM also got the superior HbA1c reduction vs. HDM at 12 week (P<0.001 and P=0.0185 in 2nd and 1st tertile respective). The results indicate the early combination therapy by acting on different pathological T2DM-related pathways such as VLDM can get more HbA1c reduction, especially for patients with higher baseline HbA1c.

Figure.

Supported By: Novartis Pharmaceuticals China

2407‑PUBFasting Triglyceride and HOMA‑IR Values Are Differently Related to HbA1c in Drug‑Naïve vs. Metformin‑Treated Patients with T2DM: An Analysis in a Large Pool of PatientsJAMES E. FOLEY, BO AHRÉN, East Hanover, NJ, Lund, Sweden

Fasting Triglyceride (TG) and HOMA-IR (H) values are surrogates of insulin resistance (IR). The current analysis was undertaken in order to assess the impact of TG and H on HbA1c values in drug-naïve (DN) or metformin (MET) treated patients with T2DM. The baseline data of DN and of MET in the pooled vildagliptin database were utilized to calculate the slope of H and TG vs. HbA1c. The slope of H relative to HbA1c was 0.09±0.13, n=1613 R2=0.07, inter-cept (INT)=4.6% in DN and 0.65±0.11, n=1904 R2=0.05, INT=−0.8% in MET. The slope of TG relative to HbA1c was 0.08±0.03, n=2445 R2=0.01, INT= 1.6% in DN

and 0.22±0.03, n=2727 R2=0.02, INT=0.5% in MET. The slope of H relative to TG was 0.55±0.05, n=1613 R2=0.13, INT= −0.03 in DN and 0.67±0.04, n=1904 R2=0.18, INT=−2.60 in MET. There was thus a much more robust increase in H (0.65 per % HbA1c) with increasing baseline HbA1c in the MET treated group than in the DN group (0.10 per % HbA1c). Both groups have an H of 5.6 at HbA1c of 9.9%. In the DN patients at an HbA1c of 6% the H is 5.2, so increasing HbA1c up to 10% is only increasing IR ~7%. On the other hand, treating patients with MET from an HbA1c of 10% to 8% is dropping H to 4.4 which is a decrease of 22% and it would be decreased by 46% down to HbA1c of 6%. There was also an increase in TG (0.22 per % HbA1c) with increasing baseline HbA1c in the MET than in DN (0.08 per % HbA1c). Both groups have a TG of 2.25 at HbA1c of 8.3%. In the DN patients at an HbA1c of 6% the TG is 2.07, so increasing HbA1c up to 8.3% is only increasing TG about 8.7%. On the other hand, reducing MET from an HbA1c of 8.3% to 6% is dropping TG to 1.75 which is a decrease of 22%. Furthermore, H is better correlated with TG in MET than DN. This study therefore shows that the relationship between TG or IR and HbA1c is different in DN and MET. This indicates that MET reduces TG and IR to a greater extent than would be predicted based upon its effect to reduce HbA1c per se. In con-trast to TG, it is surprising that H is independent of HbA1c.

Supported By: Novartis

2408‑PUBCharacteristics of Patients Initiating Empagliflozin or Other Nonin‑sulin Glucose Lowering Drugs (GLDs) in the United Kingdom (UK)SOULMAZ FAZELI FARSANI, CHRISTINA RAABE, CYNTHIA J. GIRMAN, WILL SPENCER, JYOTHIS GEORGE, PATRICE VERPILLAT, KIMBERLY G. BRODOVICZ, Ingelheim, Germany, Chapel Hill, NC, Berkshire, United Kingdom, Ridgefield, CT

Preferential prescribing of the different noninsulin GLDs can be expected based on their effectiveness and safety profiles. Assessing characteristics of patients prescribed GLDs in the real-world can provide important informa-tion to aid the conduct and interpretation of future comparative effective-ness and safety studies. The UK Clinical Practice Research Datalink (CPRD), a primary case database, was used to assess baseline characteristics of adults with T2D initiating a noninsulin GLD between Aug 2014 and Sep 2015 (1st yr of empagliflozin (EMPA) availability in the UK). Of 25,928 T2D patients, 110 started EMPA, 3,407 other SGLT2i, and 22,411 other GLDs. EMPA (mean: 56.8 years) and GLP-1a (57.6) users were younger than users of other GLDs (range: 61.0-65.0). Mean HbA1c for EMPA users (77.3 mmol/mol) was lower than for GLP-1a (80.7) and other SGLT2i (79.5) but higher for DPP-4i (73.8) and metformin (70.3) users. More patients starting EMPA, other SGLT2i, or other GLDs (range: 33.6-34.8%) had baseline diabetes complications vs. metformin (13.1%) or SU users (24.4%) which could may be explained by the shorter diabetes duration in metformin and SU initiators. Eye complications (23.6%) and hypoglycemia (10.0%) were the most prevalent diabetes mani-festations in EMPA users. Mean BMI in EMPA (35.4 kg/m2), other SGLT2i (35.2), and GLP-1a (37.7) users were higher than in DPP-4i, metformin, and SU users (range: 31.6-33.0). Mean eGFR of EMPA (95.5 ml/min) and other SGLT2i users (93.4) were higher than other groups; the lowest mean eGFR was observed for DPP-4i (80.7) and SU users (85.0). In the 1st year of avail-ability, EMPA initiators were generally younger with higher BMI and eGFR, and a higher frequency of hypoglycemia history vs. initiators of other GLDs. These early patterns of prescribing for EMPA differ from other GLDs, includ-ing other SGLT2i, need to be considered in future comparative studies and the interpretation of spontaneous safety reporting.

2409‑PUBIs the Combo of Sulfonylurea plus Metformin Appropriate for First‑Line Therapy of People Newly Diagnosed with Type 2 Diabetes and with HbA1c ≥7.6% and ≤9%?GUILLAUME CHARPENTIER, Corbeil-Essonnes, France

In 2016, dual therapy is recommended in people with type 2 diabetes (T2D), when HbA1c is ≥7.5% and ≤9%. We conducted from 2012 to 2014 a multinational multicentre open-label 3-arm superiority trial in Africa, Middle East, Russia and Latin America to compare the combination of glimepiride + metformin (G+M) vs. glimepiride (G) and metformin (M) alone in newly diagnosed T2D patients. A total of 541 were randomized (182 in the G, 177 in the M and 182 in the G+M arm). At baseline, mean age was 50.9±10.0 years, mean BMI 29.1±4.1 kg/m2, median diabetes duration 2.3 months, mean HbA1c 8.2±0.4%. Dose adjustment aimed to achieve a self-monitored plasma glucose level >70mg/dL and ≤130mg/dL without symptomatic hypoglycemia. The maximum daily dose was 4mg, 1000mg and 4/2000mg in the G, M and G+M arms, respectively. The adjusted mean change (stan-dard error) in HbA1c at month 6 was respectively -1.36 (0.07), -1.37 (0.07) and -1.50 (0.07) in the G, M and G+M arms, with non-significant difference

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between arms. The percentage of patients with HbA1c<7% was respectively 64.6%, 59.3% and 71.1% and the percentage of patients with HbA1c<6.5% 31.5%, 30.8% and 45.7%. At study end, the rate of weight decrease >5% was 3.4% (n=6), 8.2% (n=14) and 5.7% (n=10) in the G, M and G+M arms, respectively and the rate of weight increase >5% 3.9% (n=7), 1.2% (n=2) and 8.0% (n=14), respectively. Frequency of hypoglycemia episodes (any type) was mainly reported in patients receiving G. Only 5.1% of patients treated with M alone reported hypoglycemia. Severe hypoglycemia were reported in 5 patients (0.9%): 1 patient (0.5%) in the G and 4 patients (2.2%) in the G+M arm. These results suggest that G+M is effective with a low risk of severe hypoglycemia.


2410‑PUBDerangement of Hepatic Metabolism Induced by Chronic Treatment of Glucokinase Activator Contributes to Its Declining EfficacyYOSHINORI TSUMURA, YU TSUSHIMA, AZUSA TAMURA, MAKIKO HASEBE, TSUNEFUMI KOBAYASHI, Tokyo, Japan

Glucokinase (GK) in hepatocytes and pancreatic β-cells plays a key role in glucose homeostasis, and a number of GK activators (GKAs) have con-ducted clinical trials as therapeutic agents for type 2 diabetes. However, MK-0941 (MK) and other GKAs discontinued the development because of declining efficacy during chronic treatment or other issues. In our nonclini-cal study, the declining efficacy was also seen after more than 8 weeks of administration of MK in Goto-Kakizaki rats, while it was not in TMG-123 (TMG), another GKA (ADA2014#1041-P). Here, we investigated factors that make the difference in the glycemic durability between MK and TMG using Goto-Kakizaki rats. First, we evaluated the effects on pancreatic β-cell function, but chronic treatment of MK did not affect plasma insulin level and β-cell mass. Next, the effects of treatment on hepatic glucose uptake were measured by the isolated perfused liver. After single administration, the glucose uptakes were increased by both MK and TMG. However, after the chronic administration, glucose uptake in only MK-treated group was decreased compared to the control group. At this time, protein expression level of GK was decreased and G6Pase activity was increased in the liver of MK-treated group, but not in TMG-treated group. Thus, the declining effi-cacy of MK in Goto-Kakizaki rats is attributed to the derangement of hepatic glucose metabolism and not associated with pancreatic β-cell dysfunction. In the liver perfusion study, increased production of lactate and CO2 were found by single administration of MK, but not by TMG. The hepatic glucose flux analysis using 13C isotopic tracer indicated the increasing tendency of glucose uptake by both agents but the decreasing tendency of glucose release by only MK treatment. Therefore, the pharmacological effects on hepatic glucose metabolism may be different between MK and TMG. This difference may possibly relate to the different result in glycemic durability.

2411‑PUBA Combination Therapy with Liraglutide and Sitagliptin Improves Glycemic Control in Japanese Patients with Type 2 Diabetes MellitusYUKI MATSUHASHI, SHINJI CHIKAZAWA, SHOU OSONOI, SATORU MIZUSHIRI, MASATO YAMAICHI, HIDEYUKI OTAKA, KAZUHISA TAKAHASHI, AYA KANBA, KOKI MATSUMURA, KOTA MATSUKI, ERI SATO, JUTARO TANABE, MIYUKI YANAGIMACHI, HIROSHI MURAKAMI, MAKOTO DAIMON, Hirosaki, Japan

Background: Liraglutide (a glucagon-like peptide-1 analogue) and sita-gliptin (a highly-selective dipeptidyl peptide-4 inhibitor) are widely used in combination with various kinds of other oral antidiabetic drugs and insulin in Japan. We evaluated the efficacy of sitagliptin when added to liraglutide.

Methods: Japanese patients with uncontrolled type 2 diabetes mellitus (T2DM) (HbA1c>7.0%) who were treated with 0.9 mg of liraglutide subcu-taneously once daily (maximum dose in Japan) were enrolled in this study (n=17). The serum levels of HbA1c, glycated albumin (GA), fasting plasma glucose (FPG), insulin (IRI), C-peptide (CPR) and glucagon were measured. Index of insulin resistance (HOMA-R) and insulin secretion (SUIT index) were calculated using following equations; HOMA-R=IRI*FPG/405, SUIT index=1485*CPR/(FPG-61.8). Body weight (BW) and compositions (body fat mass; BFM, lean body mass; LBM) were analysed using the bioelectrical impedance analysis (BIA). 50 mg of sitagliptin was added without alter-ing previous therapy. Differences of each parameter between baseline and those 12 weeks after were calculated. Results were compared using repeated-measure ANOVA and simple regression analysis. P<0.05 was defined as statistically significant.

Result: HbA1c and GA were significantly decreased (p=0.025 and p=0.047, respectively). Simple regression analysis showed that ΔHbA1c (12 weeks-

baseline) was correlated with duration of diabetes, AST and ALT at base-line, ΔFPG, Δglucagon, ΔHOMA-R, ΔSUIT index, ΔAST and ΔALT. ΔGA was also correlated with diabetic retinopathy, AST and ALT at baseline, ΔFPG, Δglucagon, ΔSUIT index, ΔAST and ΔALT. BIA revealed that ΔGA was cor-related not with ΔLBM but with ΔBFM.

Conclusion: The present study showed that the improvement of glycemic control was correlated with liver function, reduction of glucagon and body fat mass. A combination therapy with liraglutide and sitagliptin can be effec-tive option for T2DM.

2412‑PUBDifference of Endogenous Insulin Response between Mixed‑Meal Tolerance Test and Glucagon Stress Test Is Associated with Thera‑peutic Effect of Incretin Related DrugsHIKARU TAKAMINE, YURIA NAMIKI, HIROTO SASAKI, YUYA TAKANO, KOJI INA-ZUMI, YUKO MUROHASHI, URU NEZU OSADA, Yokohama, Japan

Mixed meal tolerance test (MMT) and glucagon stress test (GST) are use-ful tests in evaluating the endogenous insulin secretion in type 2 diabetes mellitus (T2DM). We often experience the greater C peptide response (CPR-R) in MMT compared to that in GST. We assumed that this difference might partly reflect the endogenous incretin effect and be associated with thera-peutic effect of incretin related drugs (IRDs). Here, we investigated the asso-ciation between the inter-test difference in CPR-R and IRDs’ therapeutic effect. Based on our inpatient database from April 2015 to October 2016, we retrospectively extracted T2DM patients started on IRDs including DPP-4 inhibitors and GLP-1 receptor agonists. As an indicator of the endogenous incretin effect, we defined ⊿CPR-R by subtracting the CPR-R in GST from that in MMT, and analyzed its effect on the changes in HbA1c at the timing of 1 to 3 months after IRDs initiation. We also assessed the change in fasting plasma glucose (FPG) during the admission period. As the result, 89 patients were started on IRDs (male: 64%, mean age: 63 years old, mean HbA1c: 10.0%). As the primary analysis, ⊿CPR-R was positively associated with the change in HbA1c although not statistically significant (r=0.21, p=0.2). In the secondary analysis, ⊿CPR-R showed the significant and positive association with the change in FPG (r=0.46, p<0.0001). In next, in multivariate analysis adjucted with age, duration of diabetes, BMI, eGFR, CVR-R, and concomi-tant use of α-glucosidase inhibitors again showed the positive association between ⊿CPR-R and the change in FPG (β=19.7, SE=4.6, p<0.0001).

In summary, our results indicated that the patients with reduced incretin effect might be IRDs responder.

2413‑PUBTeneligliptin, a DPP‑4 Inhibitor, Decreases Plasma Levels of Three Chemokines (CCL11, CCL22, and CXCL10) during a Standardized Meal Test in People with Type 2 Diabetes, but Differently Regulates These Chemokines RespectivelyMASATO KASE, IV, TAKANORI TOMOTSUNE, SHINTARO SAKURAI, KAZU-NORI YANAGI, TERUO JOJIMA, TOSHIE IIJIMA, KUNIHIRO SUZUKI, KUNIHIRO SUZUKI, YOSHIMASA ASO, Mibu, Japan

DPP-4 rapidly cleaves not only incretin hormones but also a number of chemokines, and influences the function of chemokines. We investigated effects of teneligliptin (a DPP-4 inhibitor) on plasma levels of CCL11 (eotaxin), CCL22 (macrophage-derived chemokine; MDC), and CXCL10 (IP-10) during a meal test before and after 24-week treatment with teneligliptin in people with type 2 diabetes. We studied 10 consecutive patients with type 2 dia-betes controlled inadequately with metformin and/or sulfonylurea. A stan-dardized meal were administered at baseline and 24 weeks after treatment with 20 mg/d teneligliptin. Blood was sampled at 0, 30, 60, and 120 min after meal ingestion. We measured serum DPP-4 enzymatic activity and soluble DPP-4 antigen in addition to plasma three chemokines levels. At baseline, plasma levels of all three chemokines were significantly decreased at 60 min after a meal digestion. Either DPP-4 activity or soluble DPP-4 antigen did not change during a meal test. Treatment with teneligliptin decreased HbA1c from 8.4±1.1% at baseline to 6.8±0.5% at 24 weeks. Teneligliptin inhibited fasting serum DPP-4 activity by 90.13% compared with baseline. At 24 weeks after treatment with teneligliptin, plasma CXCL10, but not CCL11 or CCL22, significantly decreased at 60 min after a meal test. Unexpectedly, plasma levels of three chemokines were not increased after 24-week treat-ment with teneligliptin, were instead significantly decreased at every point during a meal test. Changes in fasting DPP-4 activity correlated positively with plasma levels of CCL22, but not CXCL10 or CCL11, at every point during a test meal. The counts of eosinophils significantly decreased after treatment with teneligliptin.

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In conclusion, DPP-4 inhibitors may affect chemoattractant of specific types of leukocytes by decreasing plasma levels of some chemokines. (UMIN000012508).

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2415‑PUBSingle‑Dose Pharmacokinetics and Pharmacodynamics of Sita‑gliptin, an Inhibitor of Dipeptidyl Peptidase‑4, in Healthy Indian Male SubjectsGANESH V. SANGLE, MOHAN PATIL, NITIN DESHMUKH, SHANTIBHUSHAN KAMBLE, KIRAN KUMAR VUPPALAVANCHU, SUSHIL KALE, LAYEEQ BAIG, GEETCHANDRA SINGH, JAVED SHAIKH, JITENDRA TRIPATHI, ARAVINDABABU P., Aurangabad, India

Sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor approved for the man-agement of type 2 diabetes, is reported to be more efficacious in the Indian population compared with the other ethnic groups. The aim of this study was to unravel the basis of higher efficacy by assessing the pharmacokinet-ics and pharmacodynamics (PK/PD) profile of single-dose sitagliptin 100 mg (Januvia) in healthy Indian male subjects.

In this single-centre, single-dose, cross-over, analyst-blind study, 18 healthy subjects received single dose of sitagliptin 100 mg under fasted and fed conditions. PK/PD parameters under fasting condition were analysed. PK parameters (Cmax, Tmax, t1/2, AUC0-∞, 0-t) were determined using Phoenix WinNonlin software. PD parameters [DPP-4 inhibition, active glucagon-like peptide-1 (GLP-1) and insulin] were determined using established methods.

A total of 18 subjects were enrolled [mean age, 22.4 y (range, 18-34); mean weight, 62.7 Kg (range, 51.1 - 77.0)] in the study. PK parameters expressed in mean (SD) are Cmax 491.7 (135.9)ng/mL; Tmax 2.9 (1.0)h, t1/2 10.4 (3.0)h, AUC0-∞ 4256.1 (509.9) and AUC0-t 4198.9 (500.6)ng.h/mL. The weighted average plasma DPP-4 inhibition over 24 h for the dose of 100 mg was ≥80%. At 2 h after a standard meal, mean weighted average of plasma active GLP-1 (geometric mean ratio) was 11.1 (9.9) pM/L in the sitagliptin group which is two-four fold higher compared to that reported in other populations. The mean weighted average (SD) plasma insulin levels were 29.9 (12.3) μIU/mL. No statistically significant differences were observed in PK/PD parameters under fed condition. [In this abstract only sitagliptin arm data was included]

No statistically significant differences in PK and DPP-4 inhibition param-eters were observed for Indian subjects compared to that reported in non-Indian subjects. However, observed higher GLP-1 levels may correlate with enhanced efficacy of sitagliptin in Indian population.

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2418‑PUBSubgroup Analysis to Evaluate Effect of Baseline Characteristics on Markers of Renal and Cardiovascular Risk in Type 2 Diabetes Patients Treated with SGLT2 Inhibitor (Canagliflozin)VISHAL GUPTA, VAISHALI TELI, Mumbai, India

Objective: To compare reduction in hs-crp (Highly selective c-reactive pro-tein) and serum Creatinine with respect to gender, age, baseline HbA1c, BMI and duration of diabetes.

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Methodology: Fifty patients treated with SGLT2 inhibitor (Canaglizlozin) were followed-up at months 3, 6 and 12 to evaluate change in body mass index (BMI), hs-CRP, lipid profile, creatinine and renal albumin excretion. At the end of one year, significant reduction was observed in HbA1c, hs-CRP and serum creatinine. In the present study, we assessed effect of baseline characters of age (18-40, 41-60,> 61 years), body mass index (<23, 23-27, >27 kg/m2), HbA1c (<8 or >8%), duration of diabetes (0-5, 5-10,>10 years) on reduction in hs-CRP and Creatinine. Data was represented as Mean + 2 Standard Deviation with 95% confidence interval and a p value of 0.01 or lower was considered significant. Unpaired t test and Analysis of Variance (ANOVA) was used to compare two and three sub-groups of the baseline characters respectively.

Results: Serum creatinine was significantly reduced in the male popu-lation as compared to their female counterparts (p value: 0.0025). There was a uniform reduction observed across all sg groups (p value: 0.188764), BMI (p value: 0.1974), duration of diabetes (p value: 0.135963) and baseline HbA1c levels (p value: 0.3636). There was also a uniform reduction in hsCRP observed across both genders (p value: 0.2519), all age groups (p value-0.1887), BMI (p value: 0.2839), duration of diabetes (p value: 0.83641) and baseline HbA1c levels (p value: 0.172778).

Conclusion: Male gender was associated with significant greater reduc-tion in serum creatinine at the end of 12 weeks. SGLT2 inhibitor (Canagl-izlozin) was observed to reduce Serum creatinine and hsCRP irrespective of age, baseline BMI, HbA1c, duration of diabetes.

2419‑PUBSurvey on Transition from Inpatient to Outpatient for Diabetes Patients Not on InsulinEUNICE CHUANG, JULIE KIM, HEIDEMARIE W. MACMASTER, JOSEPH S. CHANG, ROBERT J. RUSHAKOFF, San Francisco, CA, Los Angeles, CA, Berkeley, CA

Inpatient hyperglycemia is generally treated with insulin. In a previous survey, we found patients discharged to home on insulin had received appro-priate education and did well at home. However, little is known about the diabetes-specific, posthospital discharge issues that may arise for patients sent home on oral hypoglycemic agents and non-insulin injectables.

We designed and conducted a comprehensive survey (2-4 weeks post-dis-charge by telephone or online) covering predischarge issues such as survival skill education and discharge instructions, postdischarge logistical problems such as obtaining medications and supplies, glucose monitoring and overall glucose control. Patients were adult patients that spent at least 2 overnights in the hospital and sent home on any oral antidiabetic medication.

70 patients (49 phone; 30 online) completed the survey. Results in Table.

Table. Key Survey Results for Patients Discharged Home on Oral Agents and Noninsulin Injections.Medication at Admission (%)

Sulfonylurea (34.2%)

Metformin (87.3%)

TZD (6.3%) DPP-4I (13.9%) GLP-1 (5.1%) SGLT2 (3.8%) Insulin (17.7%)

Medication at discharge (%)

Sulfonylurea (36.5%)

Metformin (81.1%)

TZD (5.4%) DPP-4I (14.9%) GLP-1 (5.4%) SGLT2 (2.7%) Insulin (20.3%)

Started on Oral Agent inpatient

35% % doing Home Glucose

Monitoring

Before Hosp (92%)

After DC (78%)

% Patient told to restart Prehosp Meds

60% % not given any

instructions

26% (90% of them restarted prehosp meds)

% on DC with meds already at home

77% % Problem getting

medication

1% % on DC with HGM supplies

already at home

70% % Problem getting Strips

4%

% who Knew who to contact with problem

79% % who needed to

contact provider

21% % unable to reach provider

3%

Glucoses after DC to home (mg/dl)

First 2 days: <70

First 2 Day 70-200

First 2 days >300

2-14 days <70

2-14 days 70-200

>300

never 84%; 33% 75-99%of time; 56%

everytime

never 91% never 86%; 33% 75-99% of time; 56%

everytime

never 91%

Summary: After discharge most patients on oral hypoglycemic agents already had their medications at home and restarted them. They also had glucose monitoring testing supplies and returned to testing. Glucoses were

generally at goal with minimal highs or lows. However, despite detailed dis-charge instructions on who to call for problems and follow-up, this informa-tion appears buried and unread in the voluminous (up to >10 pages) standard discharge instructions patients receive.

2420‑PUBThe Clinical Efficacy and Safety of SGLT2 Inhibitors in Japanese Patients with Type 2 Diabetes for Two YearsTAKAHIRO TOSAKI, HIDEKI KAMIYA, AKEMI INAGAKI, MASAKI KONDO, ERIKO NAGAO, YUICHIRO YAMADA, YOSHIRO KATO, SHIN TSUNEKAWA, TATSUHITO HIMENO, TOMOYO HAYASAKI, SHIORI SATO, YUKI NAKAYA, JIRO NAKAMURA, Nagoya, Japan, Nagakute, Japan

To evaluate its efficacy and adverse effects, one of SGLT2 inhibitors (including ipragliflozin 118, dapagliflozin 49, luseogliflozin 54, tofogliflozin 36, canagliflozin 70, or empagliflozin 35) was administered to 362 outpatients with type 2 diabetes mellitus (mean age 51.8 ± 12.0 yr, diabetes duration 7.8 ± 7.0 yr, BMI 29.0 ± 4.9) with or without other antidiabetic agents for 24 months.

Average observation period was 11.7 months. The mean HbA1c level sig-nificantly improved from 7.61 ± 1.41% to 7.00 ± 0.86% at month 12 (n=212, p<0.001), but the effect was not sustained to 7.16 ± 1.13% at month 24 (n=89, p=0.006). On the other hand, body weight was significantly reduced from 78.1 ± 15.3 kg to 75.1 ± 13.4 kg at month 12 (n=212, p=0.017) and furthermore reduced to 74.2 ± 14.0 kg at month 24 (n=89, p<0.028). Systolic blood pres-sure was significantly ameliorated from 134.7 ± 16.0 mmHg to 128.1 ± 13.3 at month 12 (n=214, p<0.001), and the effect was sustained to 128.5 ± 12.8 at month 24 (n=89, p<0.001). Heart rate, estimated visceral fat area, waist circumference and uric acid also improved significantly. Urinary albumin/creatinine ratio and eGFR did not show remarkable changes. A significant increase was observed in serum HDL cholesterol from 49.4 ± 12.7 to 53.4 ± 15.7 at month 24 (n=78, p=0.018). Serum alanine aminotransferase was significantly improved from 37.4 ± 28.3 U/L to 30.0 ± 22.0 at month 12 (n=192, p=0.002). This amelioration was not related to the improvement of HbA1c, but the reduction of body weight.

A total of 48 adverse events were noted, including non-severe hypoglyce-mia (n=14), pudendal pruritus (n=4), urinary frequency (n=7), a strong hunger sensation (n=3), nausea (n=2), constipation (n=2), itching sensation (n=2), lightheadedness after alcohol drinking (n=2), systemic eruption (n=1) and cerebral infarction (n=1).

SGLT2 inhibitors seemed useful in the treatment of Japanese patients with type 2 diabetes mellitus for 2 years.

2421‑PUBEffect of Multimodal Approach with Newer OAD’s on Glycemic Parameters and Insulin Dose in Indian Type 2 DM Patients Uncon‑trolled on InsulinBALAJI JAGANMOHAN, SR., CHETAN PATIL, JR., ANJANA RAMAMURTHY, JR., VAMSI KOLUKULA, SR., Bangalore, India, Mumbai, India, Hyderabad, India

Aim: To evaluate the effect of add on therapy with newer oral antidiabetic (OAD) agents in type 2 diabetes mellitus (T2DM) patients uncontrolled on insulin.

Method: Total 20 T2DM patients uncontrolled on insulin and treated using multimodal approach by addition of newer OADs were analysed retrospec-tively. Mean daily dose (MDD) of antidiabetic drugs, HbA1c, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) were analysed after 3 months of multimodal approach therapy.

Results: Mean age of patients was 61.25±12.86 years, with 60% of male. Among these 80% of patients were suffering from diabetic peripheral neu-ropathy. Complications like, retinopathy, microalbuminuria, acanthosis and cataract were present in 35%, 20%, 15%, 5% patients respectively. MDD of OADs at baseline and at 3 months are given in the Table. HbA1c, FPG and PPG reduced significantly by 1.83%, 51.75 mg/dl and 58.44mg/dl respec-tively from their respective baseline of 9.4 ± 1.6%, 176.9 ± 65.24 mg/dl and 236.4 ± 71.02 mg/dl (P- .0001, .0029, .0234 respectively). MDD of insulin was reduced significantly from 48.10 IU to 28.30 IU (mean difference: -19.8IU; p-.0001).

Conclusion: Multimodal approach with newer OADs significantly improved glycaemic control in previously uncontrolled T2DM on insulin therapy with a remarkable reduction in daily insulin dose.

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Table. Mean Daily Dose of Antidiabetic Drugs.Oral antidiabetic drug At Baseline At 3 months

N Mean daily dose (mg)

N Mean daily dose(mg)

Metformin 15 1603.3 19 1526.32Glibenclamide 1 10 — —Gliclazide 2 180 6 136.67Glimepiride 9 4.6 14 3.64Pioglitazone 3 27.5 3 7.5Saxagliptin 1 100 — —Sitagliptin 1 100 4 100Teneligliptin 2 20 2 20Vildagliptin 7 85.7 4 100Linagliptin — — 4 5Gemigliptin — — 4 50Acarbose 1 50 — —Voglibose 3 0.5 — —Canagliflozin — — 8 100

2422‑PUBFour‑Year Outcomes of DPP‑4 Inhibitors and Glinides Combination TherapyMASAYUKI HIRAMA, TOKIKO UEHARA, SHINYA KANEKO, YOSHIHIKO YAMADA, Atami, Japan

Object: Sulfonylurea (SU) use has been linked with increased risk of mac-rovascular disease. However, SUs are widely used. We focused on DPP-4 inhibitors and glinides combination therapy as an alternative to SUs. DPP-4 inhibitors, do not usually cause hypoglycemia. Glinides improves postpran-dial hyperglycemia. DPP-4 inhibitors and glinide are seemed to be ideal combination for the purpose of avoiding macrovascular complications. We verify the efficacy and safety of switching to DPP-4 inhibitors and glinides combination therapy from SUs.

Methods: This study was a Single center, retrospective, observational study that assessed the efficacy and safety of DPP-4 inhibitors and Glinide combination therapy. Switchers who were switched to Vildagliptin and Glinides (Nateglinide or Mitiglinide) Combination therapy from SUs, were compared to “Continuers” who continued using SUs. Cohorts were matched by 1:1 propensity score matching to compare 4-year outcomes (18 patients in each cohort, mean HbA1c 8.35±1.38%, mean BMI 23.6±4.6, mean duration of diabetes 8.2±6.8 years in switchers and mean HbA1c8.2±1.57%, mean BMI 24.0±3.9, mean duration of diabetes 8.2±4.8 years in continuers).

Results: At 4 years, the mean changes in HbA1c from baseline were -0.86% ± 0.9% vs. +0.1% ± 0.8% in Switchers vs. Continuers, respectively (P =0.02). Hypoglycemia risk was lower with Switchers (n=2) vs. Continuers (n=9). Body Weight decreases in Switchers (mean:-0.7kg), While increases in Continuers (mean: +2.3kg).

Conclusions: The study suggests that switching to DPP-4 inhibitors and glinides combination therapy from SUs may improve glycemic control with-out increasing risk of hypoglycemia and undesirable weight gain.

2423‑PUB

2424‑PUBSodium‑Glucose Cotransporter‑2 Inhibitors as Treatment for Diabe‑tes Mellitus Type 2 in a Cohort of Patients Who Suffer Heart FailureJOSE IGNACIO MORGADO GARCIA DE POLAVIEJA, JESSICA ROA-GARRIDO, PILAR RODRIGUEZ ORTEGA, JOSE FRANCISCO DIAZ FERNANDEZ, Huelva, Spain

Introduction: Recently, it has been discovered a Sodium-Glucose Co-Transporter-2 Inhibitor (SGLT2-inhibitor) which has reduced cardiovascular mortality and hospitalizations due to HF. We do not know best treatment of DM in these patients yet.

Purposes: To evaluate safety and efficacy of SGLT2 inhibitors in a cohort of patients with T2DM and HF.

Methods: A Prospective, observational, study on T2DM patients with gly-cohemoglobin: A1c higher than 6.5% with oral antidiabetic medications and HF (admission in the last 6 months or high levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) in addition to HF symptoms). SGLT2 inhibi-tors were started at stable situation (same treatment of HF in the last 3 months). We assessed metabolic control, HF situation and safety (hypogly-caemia).

Results: We analyzed 11 patients, 7 receiving canagliflozine, 3 empagliflo-zine and 1 dapagliflozine. Basal characteristics: Mean age 66.4 ± 8.6 years. Mean LVEF was 40.4±10%, mean NT-proBNP level: 1430±1243 pg/mL, mean of dose of furosemide was 52.7 ±38.2 mg daily. Mean BMI: 27.9 ± 4.2 kg/m2 and A1c 8.45 ± 1.43%. Follow-up (120 days): A significant reduction was observed in NT-proBNP values (mean 912± 900 pg/mL, p=0.018), BMI (mean 26.2±3.9 kg/m2, p=0.001), A1c (mean 7.5±0.8%, p= 0.012) and dose of furose-mide (mean 49.1 mg±37.3 mg daily, but p=0.34). Furthermore, it was reduced the rates of admission for HF (from 1.1±0.8 120 days before the treatment to 0.01±0.3 120 days after, p=0.002).

Conclusions: This pilot study shows the beneficial effects of SGLT2 inhibi-tors in patients with Heart Failure, improving metabolic control and HF situ-ation. This study has several limitations, such as small sample size and short follow-up. So, further studies, specially randomized trials, are required to contrast these hypotheses.

2425‑PUBA Clinical Case Series of Use of SGLT2 Inhibitors as a Add‑On Ther‑apy in Patient with T2DM and HIVSOWMYA CHANDRA REDDY, KULSUM BANO, PAPITA ROZARIO, WILLIAM MOORE, AMY H. WARRINER, Birmingham, AL, Little Rock, AR

Background: People living with HIV (PLWH) frequently develop diabetes mellitus (DM), prediabetes, and metabolic syndrome. PLWH are believed to be at high risk for metabolic disorders due to both traditional risk factors, such as age, sex, obesity, as well as risks of HIV infection and antiretro-viral therapy. SGLT2 inhibitors have been associated with an improvement in HbA1C, diabetic nephropathy, blood pressure and weight loss in studies among HIV-negative persons. Here, we review a case series of patients with DM and HIV who were initiated on SGLT2 inhibitors to evaluate the effec-tiveness and safety of this class of drugs on glycemic control, weight, blood pressure changes, side effect profile, and tolerance.

Methods: PLWH with DM who were started on an SGLT2 inhibitor during routine clinical care, seen in a tertiary care HIV endocrinology clinic, were selected for the case series (N=19) during a 2-year study period. Data on demographics, DM treatment, metabolic and biochemical variables were collected retrospectively.

Results: Mean age of the patients was 49.7 years (SD 8) of which 58% were males and 42% females; 68% African American and 32% Caucasian. The mean duration of diabetes was 7.9 years (SD 6.2), mean baseline HbA1c 9.1% (SD 2.1). Mean HbA1c decreased 0.9% (SD 1.6), weight decreased by mean 3.4 kg (SD 6.6). A decrease in systolic blood pressure was seen in one-third of patients. Up to 50% of the patients developed a GU infection, pre-dominantly in women. Approximately half of the patients stopped the SGLT2 medication with reasons including acute kidney injury, polyuria, hyperkale-mia, and incontinence. There was no significant change in CD4 seen in any of the patients.

Conclusion: Our study found that use of SGLT2 inhibitors appears safe and effective in PLWH. We found that there is significant decrease in HbA1c when used as add-on therapy. No unexpected adverse events were seen.

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CLINICAL THERAPEUTICS/NEW TECHNOLOGY—PHARMACOLOGIC TREATMENT OF COMPLICATIONS

CLINICAL THERAPEUTICS/NEW TECHNOLOGY—PHARMACOLOGIC TREATMENT OF COMPLICATIONS

2426‑PUBClinical Dashboard to Evaluate and Monitor Institutional Quality and Effectiveness of Diabetes Crisis ManagementKALMAN E. HOLDY, JACQUELINE S. THOMPSON, ANGELIC M. MELLINA, DOROTHY WAGEMESTER, MARTY ENGLE, CAROLYN COX, San Diego, CA

The algorithm for diabetes crisis (DKA/HHS) treatment is well estab-lished, but practices vary widely. Few studies systemically compare prac-tices. We are systematically measuring DKA/HSS care and report our ini-tial dashboard examining 2,700 admissions over 4 years. Table 1 lists the dashboard variables, updated quarterly. Cases are identified by diagnostic codes for DKA/HHS and/or use of specific order sets. Microsoft Excel and Tableau Software are used for analysis. Figure 1 displays selected items. The dashboard presents data to frontline caregivers to decrease variations and measure effectiveness of improving the application of the DKA/HHS algorithm. We are improving the dashboard by adding variables such as the time spent in the ER, the time to start insulin infusion, and the time transfer from the ICU. 2427‑PUB

Determination and Evaluation of Hypertension in a Nonhuman Pri‑mate Model of Type 2 DiabetesYINAN LIANG, ZUNYUAN YANG, ZHIGANG LIANG, YANQIN YU, YUANHAI CHEN, ZUNWEI YAO, YUBO SHEN, BARBARA C. HANSEN, LI GONG, WEN ZENG, Chengdu, China, Gulfport, FL

The common rat and canine hypertensive models do not fully reflect important functional and structural features of hypertension in humans. We have estab-lished NHP standards for normal blood pressure in a colony of 208 adult rhesus monkeys and carried out a preliminary study of the efficacy of the combination anti-hypertensive drug, Entresto (sacubitril/valsartan) in rhesus monkeys with type 2 diabetes (T2DM). Blood pressure, fasting plasma glucose (FPG), HbA1c, total cholesterol (TC) and triglycerides (TG) were measured under ketamine anesthesia. To determine the normal range of blood pressure in adult rhesus monkeys, we excluded those meeting the following criteria: age <7 yrs or >15 yrs; SBP >140 mmHg or DBP >90 mmHg; body weight >14 kg; FPG >5.5mmol/L or HbA1c >4.5%; TG >1.1 mmol/L or TC >4.75 mmol/L. In the remaining 57 monkeys, considered to be healthy and normal, the normal blood pressure for NHPs was determined to be: SBP: 119±2 mmHg; DBP: 58±1 mmHg, Mean±SE. To com-pare efficacy in humans to rhesus, recently approved drug to treat heart failure, Entresto, also shown to be beneficial for the control of blood pressure, was used to evaluate efficacy in hypertension in the rhesus monkey model of mild T2DM. Six male monkeys (age: 14.2±1.0 yrs; FPG: 101.2±1.5 mg/dL; SBP: 140±2 mmHg; DBP: 67±3 mmHg) were randomly assigned to the Entresto group (N=3, p.o., 6.48/6.85mg/kg, q.d.) or to the vehicle group (N=3, vehicle p.o., q.d.). After 3 months of treatment, the blood pressure of the Entresto group was significantly lowered (SBP: -18.62%; 140±5 to 114±1 mmHg, p<0.05 and DBP: -18.30%; 68±6 to 56±1 mmHg), while the vehicle group were unchanged (SBP: 40±2 to 134±5 mmHg; DBP: 66±2 to 64±2 mmHg; p’s=NS).

In conclusion, NHPs have similar normal blood pressure to humans, simi-larly develop spontaneous hypertension, and respond to this antihyperten-sive drug similarly to humans, thus providing an excellent animal model to validate the efficacy of anti-hypertensive drugs.

2428‑PUBEffect of Fenugreek Furostanolic Saponin on Cardiometabolic Parameters in Obese SubjectsSREEJAYAN NAIR, DEREK SMITH, ANAND NAIR, RAMA NAIR, DEBASIS BAGCHI, ANAND SWAROOP, Laramie, WY, St. Louis, MO, Houston, TX, Piscataway, NJ

We have recently reported that furostanolic saponins (FS) from the spice fenugreek, improves insulin sensitivity, reduces blood glucose and has a broad safety profile. In this study, we evaluated the effect of FS on cardiometabolic parameters in obese subjects. In this randomized, double-blind, placebo-controlled, study, 28 male or female subjects with body mass index >25 Kg/m2 and satisfied one of the following 3 criteria, HbA1c >5.6%, 2 h-post-challenge glucose > 125 mg/dL, HOMA-IR > 2.5, were randomly assigned to receive either placebo or FS (Fenfuro-TM, 500 mg bid) capsules for 12-weeks. Blood pressure, body weight, DEXA, glucose tolerance, serum lipids, and markers of inflammation and oxidative stress were assessed. HOMA-IR and serum 8-isoprostane were significantly lower in in subjects receiving FS. No significant changes were observed in any other parameters. Collectively, this pilot study suggests that fenugreek furostanolic saponins may improve insulin sensitivity and oxidative stress in overweight subjects.

Supported By: National Institute of General Medical Sciences (1U54GM104944-01A1 to S.N.)

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HEALTH CARE DELIVERY—ECONOMICS


2429‑PUBEffects of Pharmacist‑Led Community Diabetic Care Using a Digital Solution in China: A Retrospective Analysis of Large, Real‑World SamplesYINGJIE LI, ZHEN WANG, YING CHEN, KAI LIU, Shanghai, China

Objective: To identify the effects of diabetes management using a digital solution by retail pharmacists for diabetic patients in a retrospective, obser-vational analysis.

Methods: We developed a digital healthcare solution that includes Blue-tooth-enabled glucose meter, a mobile App, and a cloud database with 5 different algorithms for diabetic care support. This solution was commer-cialized and deployed in 1,146 retail pharmacies of 165 brands in 94 cities in China to help pharmacists manage diabetic patients who were their pharmacy members. During Jun 6th 2015 to Nov 4th 2016, a total of 85,790 patients received in-store diabetic care and 3,653 of them were selected in this analysis following 4 inclusion criteria: 1) baseline fasting blood glucose (FBG) ≥ 7.0 mM or baseline random blood glucose (RBG) ≥ 7.8 mM, 2) the intervention duration between the first- and last-time diabetic care was ≥ 1 month, 3) the number of received diabetic care was ≥ 3 times, and 4) the baseline characteristics were complete. Among them, 1,657 received FBG tests, 2,286 had RBG tests and 290 had both.

Results: FBG and RBG were reduced on average by 0.8 mM (baseline: 9.1 ± 2.1 mM, last time: 8.3 ± 2.2 mM, n=1,657, P< 0.001) and 1.5 mM (base-line: 11.3 ± 3.4 mM, last time: 9.8 ± 3.4 mM, n= 2,286, P<0.001), respectively. Disease staging was improved with 482 patients of the FBG population (29.1%) and 709 patients of the RBG population (31.0%) returning to normal. The predominant glycemic control effect occurred after the first-time inter-vention, and the BG level remained stable throughout the follow-up. Simula-tion analysis revealed linear descending relationship of both FBG and RBG to time, and the concentration distributions were moving towards the normal BG level. The linear fitting functions were: FBG, Y = -0.010x + 7.832; RBG, Y = -0.018x + 9.574.

Conclusion: Digital healthcare solution is effective in assisting retail phar-macists to deliver community diabetic care in real world.

2430‑PUBImpact of an Integrated Clinical Pharmacy Service on Hemoglobin A1c Reduction at a Federally Qualified Health CenterBENJAMIN CHAVEZ, EMILY KOSIROG, MARILYN BANH, Aurora, CO

Purpose/Background: Clinical pharmacy services (CPS) have been on the rise lately with increasing data being published on their outcomes. However, data on these types of services in low-income settings, such as federally qualified health centers, is scant. This study aims to measure the impact of one such service on patients with diabetes. Patients in this health center are referred for one-on-one CPS by their primary care provider to manage specific disease states, with most those referrals being for the management of diabetes. Pharmacists can initiate and modify medication therapy, order laboratory tests, and recommend lifestyle changes per collaborative prac-tice agreement.

Methods: Patients diagnosed with diabetes who had an initial visit with the CPS team between July 1, 2015 and March 31, 2016 were included in this study. Individual charts were analyzed for improvements in hemoglobin A1C (HbA1c), improvements in blood pressure (BP), number of visits, and specific medication use. Data for these patients was collected through September 30, 2016.

Results: A total of 250 patients were identified for review; 211 had a pre- and post-pharmacy intervention HbA1c. The average pre-intervention HbA1c was 10.7% +/- 2.5%; the average post-intervention HbA1c was 9.3% +/- 2.1% (p<0.0001). Patients whose pre-intervention HbA1C was > 9% had a statistically greater decrease of 1.8% (p<0.0001) than patients with a base-line HbA1c of < 9%. A significant correlation was found between number of visits and HbA1c difference. Statistically significant BP reductions were also found in patients who were hypertensive when they began CPS.

Conclusion/Implications: Patients with diabetes who had one-on-one visits with clinical pharmacists had significant improvement in their HbA1c and BP. Data suggests that patients with a HbA1c > 9% may benefit more from this interprofessional consultation. This collaborative care model and outcomes could be replicated at other institutions.

2431‑PUBA Real‑World Comparison of Outcomes in Patients Receiving Three Oral Antihyperglycemic Therapies, GLP‑1, or Basal Insulin: An Analysis of Electronic Medical Record DataLAWRENCE BLONDE, ELISHEVA LEW, DENIS RACCAH, JULIANA MEYERS, MAYANK AJMERA, KEITH DAVIS, MONICA BERTOLINI, BRUNO GUERCI, New Orleans, LA, Paris, France, Marseille, France, Research Triangle Park, NC, Durham, NC, Vandoeuvre-les-Nancy, France

Objectives: Many treatment guidelines tend to recommend and clinicians usually follow a stepwise approach that may not be ideal as patients may experience uncontrolled HbA1c between steps. Achieving HbA1c control earlier and maintaining control longer is a key goal of T2DM treatment. To assess treatment in a real world setting, this study compared outcomes in patients with uncontrolled T2DM receiving 3 oral antihyperglycemic (OAD) therapies, GLP-1, or basal insulin (BI) with a retrospective electronic medical record database.

Methods: Patients with a T2DM diagnosis between 1/1/2007 and 12/31/2014 were identified in the GE Centricity database. Patients receiving 3 OAD’s, GLP-1, or BI were selected (sequential or simultaneous initiation of 3 OAD’s, GLP-1, or BI termed index date). Patients were required to have 6 months pre- and 12 months post-index date physician history and a pre-index date HbA1c >7%. HbA1c was compared between the 6 months pre- and 12 months post-index date.

Results: A total of 59,598 patients met the inclusion criteria (23,450 3 OAD’s, 8,023 GLP-1, and 28,125 BI). The BI cohort had a higher baseline HbA1c (mean [SD, median] 9.7 [2.0, 9.2]) vs. 3 OAD’s (8.7 [1.5, 8.2]) or GLP-1 cohorts (8.7 [1.4, 8.3]) (P<0.0001). The BI cohort had the largest decrease in HbA1c during follow-up (i.e., decrease of 1.4% for BI indicating a 14.0% change, 0.85/9.8% for 3 OAD’s, and 0.9/10.3% for GLP-1). Despite such marked HbA1c decrease, 46.5% of patients in the BI cohort, 33.6% in the 3 OAD’s cohort and 34.1% in the GLP-1 cohort had Hba1c > 8.0% during follow-up.

Conclusions: In a large clinical practice database, despite improvements in HbA1c, over a third of patients had HbA1c > 8% during follow-up, advocat-ing the desirability of new treatment options or earlier more intensive use of present therapies that could provide more robust and sustained glycemic control.

Supported By: Sanofi-Aventis

2432‑PUBCost Effectiveness Analysis of a Flash Continuous Glucose Monitor‑ing System for T1DM Patients Receiving Intensive InsulinRICHARD HELLMUND, BIJU VARUGHESE, Alameda, CA

Background: A novel, factory-calibrated flash continuous glucose monitor-ing system (FreeStyle Libre™ system) has features compared with other con-tinuous glucose monitoring (CGM) devices that may impact payer value. An initial cost-effectiveness analysis has been performed to assess the value of flash CGM compared with specialized CGM for T1DM patients receiving intensive insulin.

Methods: The IMS Core Diabetes Model was run over a 50-year horizon, modelling a population reflecting the IMPACT study cohort (Bolinder, 2016). Efficacy in terms of HbA1c and hypoglycemia was assumed to be the same for both technologies due to a lack of reliable comparative data. Flash CGM has a utility benefit (0.03; Matza, 2015) given the 91% reduction in self-mon-itoring of blood glucose (SMBG) in IMPACT. This benefit was not applied to specialized CGM since SMBG tests are required for calibration. CGM costs were added to the SMBG annual costs in IMPACT. Flash sensor cash price was €59.90 (up to 14 days). CGM costs were €6124 (year 1) and €5400 (later years).

Results: Flash CGM was associated with 42% less direct cost and a 0.63 increase in QALYs.

Table.Flash CGM Specialized CGM Increment

Direct costs $136,546 $233,530 -$96,983LY 20.72 20.72 0.00QALY 12.93 12.30 0.63

Conclusions: This initial analysis shows flash CGM may be better value than specialized CGM for T1DM patients receiving intensive insulin. More work, including scenario testing, is needed to assess the value of these technologies.


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2433‑PUBCost Calculation and Real‑World Use of a Flash Continuous Glucose Monitoring System for Patients Using Intensive Insulin: A UK NHS PerspectiveRICHARD HELLMUND, Alameda, CA

Background: A real-world dataset has been created from utilization of a novel, sensor-based flash continuous glucose monitoring system (FreeStyle Libre™ system). When users scanned their sensor with a reader, they col-lected up to 8 hours of glucose readings that could be uploaded via internet-connected PC-based software to a de-identified database. A cost calculation is presented from a UK NHS perspective based on the real-world scanning frequency observed, comparing the acquisition cost of the flash monitoring system with SMBG for patients receiving intensive insulin.

Methods: Unit costs were £0.04 per lancet and £0.29 per strip, and the sensor cash price was £48.29 per sensor. Sensor duration is up to 14 days. RCTs in T1DM and T2DM patients receiving intensive insulin showed patients who used the flash monitoring system also used 0.3-0.5 SMBG tests/day on average.

Results: The real-world data showed the mean scan rate per day was 16 per patient (median = 14), based on over 50,000 readers uploaded to the dataset. Annual cost of 16 SMBG/day is £1927.20 per patient compared with £1255.54 per patient for flash monitoring sensors. The annual cost of addi-tional SMBG tests for patients using flash monitoring is £60.23, assuming 0.5 SMBG/day. The aggregate cost of glucose monitoring for flash monitor-ing system users is £611.43 (32%) less than for SMBG users.

Conclusion: To achieve the rate of real-world glucose monitoring for SMBG users that has been observed for flash monitoring system users would cost the UK NHS an additional £611.43 per patient per year. Com-pared to SMBG, flash monitoring is an affordable system to enable patients using intensive insulin to check their glucose frequently as recommended in clinical guidelines.


2434‑PUBEffectiveness of Team‑Based Diabetes Care in Urban CambodiaSOVANN PENG, PHANAVARINE MENH, NAOMI BYRNE-SOPER, MARIE E. MCDONNELL, PETER CURRAN, MARGO HUDSON, Phnom Penh, Cambodia, Boston, MA, Ketchum, ID

Background: Diabetes (DM) incidence in southeast Asia is expected to rise by 70% in the next 20 years. In Cambodia (KH), over 200,000 people have diabetes and more than half are undiagnosed. Barriers to care include pov-erty, high out-of-pocket costs, and lack of coordinated team-based chronic disease management with trained specialists. We assessed outcomes of a new team-based DM program (TBDP) in urban KH.

Methods: The HOPE Worldwide Medical Centers in Phnom Penh (PP) started its first TBDP in 3/2013 funded by donations and patient co-pay-ments. Personnel includes 4 MDs (internists), 2 RN educators, and 2 data analysts. The model provides RN/MD co-visits, staff training programs, and support/group education for patients.

Results: A total of 1,111 new pts were enrolled in an electronic registry from 7/2015-6/2016 and follow-up data were collected through 11/2016. Of those enrolled, 93% had T2DM, 1% T1DM and 6% pre-DM. 36% were previ-ously undiagnosed. Mean age was 57.9 ± 10.7, BMI 24.2 ± 4.1, 67% female and 66% lived outside of PP. Mean baseline A1c (N=1091, 98%) was 9.0 ± 2.5. A1c was >7 in 75% and >9 in 43%. 7% of pts were taking insulin alone, 3% insulin and orals, and 74% on oral meds only. While 891 (80%) pts had at least 1 return visit, only 317 (29%) had a follow-up A1c. Over 12 months, the overall mean absolute A1c change was -1.73 (P<0.001) and for pts with A1c >7%, -2.25 (p <0.0001). Of those with A1c >9 at baseline, 84% had a change of -1% or greater.

Conclusions: A TBDP was highly effective in lowering A1c in a low income, under-resourced Southeast Asian setting. Factors that may have influenced outcomes include ability to attract and retain a large cohort, cost-sharing between the institution and patients, and selective utilization of follow-up A1c testing. Cost may be a factor in low follow-up testing rates and further research to address this is warranted.

Supported By: PECO Foundation

2435‑PUBThe Efficacy, Safety, and Cost Effectiveness Evaluation of Dipepti‑dyl Peptidase‑4 Inhibitors in Patients with Type 2 DiabetesYUFEI FENG, TING LI, LEI XU, XUELIN SUN, XIN HU, Beijing, China, Shenyang, China

Objective: To evaluate the efficacy, safety and cost-effectiveness of the five dipeptidyl peptidase-4 inhibitors (Alogliptin, Linagliptin, Saxagliptin, Sitagliptin, and Vildagliptin) in patients with type 2 diabetes mellitus.

Methods: Search of Medline and Embase databases was conducted to identify qualified studies in which DPP-4 inhibitors (DPP-4i) were used as either monotherapy or dual therapy (plus metformin). The primary out-comes were the mean change of HbA1c from baseline and the proportion of patients achieving the goal of HbA1c <7%. The secondary outcomes included the mean change of body weight and the ratios of patients experiencing hypoglycemia. All the available data from the qualified studies were com-pared via network meta-analysis. The binary or continuous models based on Bayesian model with random effects were used. Cost-effectiveness analy-sis was performed with the setting of pricing in China.

Results: No significant differences were found in the HbA1c reduction and the proportion of patients achieved the goal of HbA1c <7% among five DPP-4 inhibitors, whether as monotherapy or combined with metformin. DPP-4i in general do not significantly increase the risk of hypoglycemia when used as monotherapy or dual therapy with metformin compared to placebo. Cost-effectiveness analyses showed that to reduce HbA1c by 1%, the annual cost of Alogliptin is the lowest among DPP-4i when used as monotherapy or combined with metformin. On the other hand, for every additional 1% HbA1C reduction on top of metformin, Vildagliptin exhibits the lowest cost.

Conclusions: All these five DPP-4 inhibitors show good efficacy, safety and economic affordability. With the price setting in China, Alogliptin exhibits the lowest cost for every 1% HbA1c reduction when used as monotherapy or combined with metformin while Vildagliptin shows the lowest cost for every additional 1% HbA1c reduction on top of metformin.

2436‑PUBClinical Outcomes of Patients with Type 2 Diabetes Mellitus in a Student‑Run ClinicNAVREEN K. PANDHER, FANGLONG DONG, KAY FANGEROW, AIRANI SATHANANTHAN, Pomona, CA, Montclair, CA

The purpose of this study is to assess clinical outcomes based on ADA Standards of Care in a student-run clinic for uninsured patients with type 2 diabetes mellitus (T2DM). A retrospective chart review was conducted for T2DM patients who sought care between 2014 and 2016. Data was collected at 3 time points: initial, a visit within the past 2 years, and the latest visit. Among the 39 patients included, 64.1% were females, 94.9% Hispanics, and the mean age was 53.9 + 9.6 years. The average patient had diabetes for 7.1 years. Comparing the most recent visit with the oldest visit, the mean weight decreased by 3.5 pounds (P=0.0297). Cholesterol, triglyceride, and LDL decreased by 8.91 (p=0.0687), 12.05 (P=0.1724), and 6.42(P=0.3222) respec-tively. The average BMI decreased by 0.93 (p=0.0137). However, the average A1c increased from 7.45 (SD=1.40) to 7.77 (SD=1.63) and the HDL decreased by 2.57 (P=0.0565). At the most recent visit, 25.6% had an elevated blood pressure. Over the last 2 years, each patient received 6.4 foot exams on average. 11 of the patients were documented to have received a referral for an eye exam since their initial visit. 51.3% (28.6% moderate intensity) were taking a statin, 26.3% were on aspirin, and 66.7% were on an ACEI at their most recent visit. 8.3% of patients were documented to have received a flu vaccine at the clinic within the past year. Noncompliance with lifestyle changes and pharmacological treatment was reported by 48.7% and 76.9% respectively, with 41.2% reporting financial reasons for noncompliance.

In conclusion, T2DM patients at a student-run clinic in Montclair, Califor-nia reached goals for medical history, physical exam, and lab evaluation with room for improvement in eye exams, immunizations, and self-management. Status of eye exams and noncompliance for self-care could be explained by a higher cost for specialty visits and medications. Overcoming financial cost may help improve these measures and enhance long term outcomes.

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2437‑PUBLong‑Term Impact of Early and Sustained A1c Control on Clini‑cal and Economic Outcomes: U.S. Veterans Health Administration (VHA) Database AnalysisFURAHA KARIBURYO, TAO FAN, LIN XIE, ADESUWA OGBOMO, ONUR BASER, PHILIP LEVIN, Ann Arbor, MI, Bridgewater, NJ, New York, NY, Towson, MD

Research has shown that effective A1c control in patients (pts) with T2D is associated with better clinical outcomes, while pts with poorly controlled A1c incur higher healthcare costs. This retrospective study evaluated the impact of sustained A1c control and time-to-A1c control after T2D diag-nosis on clinical and economic outcomes. The VHA database was used to identify pts diagnosed with T2D between Oct 1, 2006, and Sep 30, 2009. Index date was defined as first observed A1c record on or after Oct 1, 2006. Participants needed to have ≥6 years of data: 1-year pre-index period (with no insulin prescription or >2 OADs); 2-year assessment period during which A1c sustainability was assessed; and ≥3-year follow-up period. Economic and clinical outcomes were compared for pts with sustained A1c control vs. those with uncontrolled A1c (every A1c measurement <7.0% vs. ≥7.0% dur-ing the assessment period), and for pts with early A1c control vs. late control (A1c<7.0% during the whole assessment period vs. last 6 months only). Study sample yielded 45,379 pts with early and sustained A1c control, 14,491 with uncontrolled A1c, and 4,456 with late A1c control. Over the 3-year follow-up period, pts with sustained A1c control had lower total diabetes-related costs (−$3,877; P<0.0001) and lower total diabetes complications-related medical costs (−$1,393; P<0.0001) vs. pts with uncontrolled A1c. Early A1c control resulted in lower diabetes-related costs (−$3,385; P<0.0001) and lower total diabetes complications-related medical costs (−$674; P=0.0106) vs. pts with late A1c control. Uncontrolled A1c was associated with a 17% higher risk of diabetes complications (95% CI=1.13-1.22; P<0.0001) and late control with a 14% higher risk (95% CI=1.07-1.21; P<0.0001). This real-world study suggests that early and sustained A1c control in pts with T2D can have long-term benefits including reduced risk of diabetes-related complications and lower diabetes-related costs.

Supported By: Sanofi U.S.

2438‑PUBIndirect Costs and Quality of Life for Patients with Type 2 Diabetes in SingaporeKIAT MUN SERENA LOW, SU CHI LIM, XIAO ZHANG, JUANPING YANG, SU JIAN DARREN YEO, KUE LOONG KEVEN ANG, TAVINTHARAN SUBRAMANIAM, CHEE FANG SUM, Singapore, Singapore

Despite growing prevalence of diabetes globally, information of its eco-nomic burden, particularly indirect cost and health-related quality of life (HRQoL), is scarce. We aim to study the indirect costs and HRQoL of patients with type 2 diabetes (T2D) in Singapore. This is a cross-sectional study using questionnaire survey administered on 203 patients with T2D who attended a Diabetes Centre in a hospital in Singapore in 2016. We used a human capital approach to calculate costs of absenteeism and presenteeism. Health utility scores and Visual Analog Scale (VAS) with 100 representing ‘best imagin-able health state’ and 0 ‘worse imaginable health state’ were derived from EuroQol (EQ) 5D. Kruskall Wallis and Mann Whitney U-tests were performed to compare costs and health utility scores between groups. Spearman cor-relation was used to examine relationship between costs and health utility scores. The median workdays lost annually related to absenteeism and pre-senteeism were 4 days and 28 days respectively. The median annual costs of absenteeism and presenteeism were USD 16 and USD 146 respectively. The median EQ-5D index and EQ VAS scores were 0.83 and 70 respectively. The absenteeism costs tended to be lower in patients with lower socio-economic status in terms of education (p<0.001), housing (p=0.007) and occupation (p<0.001). The presenteeism cost correlated moderately with EQ-5D index (r=-0.37; p<0.001). Patients who were single and not working tended to have lower EQ-5D index score than those who were married and working (p=0.02 and p=0.004 respectively). The EQ-VAS score was lower in those with poorer socio-economic status in terms of education (p=0.03), income (p=0.01) and occupation (p=0.016). Presenteeism contributed more substantially to indirect costs than absenteeism. The results provide useful baseline for comparing with future follow-up studies on patients with T2D and raise awareness of the impact of T2D on work productivity and HRQoL in Singapore.

Supported By: Alexandra Health (STAR/16102)

2439‑PUBPreoperative Optimization of Glycemic ControlCARLOS E. MENDEZ, NJERI WAINAINA, KURT PFEIFER, BARBARA SLAWSKI, Milwaukee, WI

It is well established that hyperglycemia the day of, during, and after surgery predicts poor clinical outcomes. The section of Perioperative and Consultative Medicine at the Medical College of Wisconsin has designed an innovative initiative aimed to improve glycemic control in patients with diabetes prior to elective surgeries. This comprises a nested preoperative diabetes clinic staffed by a physician diabetologist where patients with poor glycemic control are scheduled for evaluation and intensification of diabetes regimens. Appointments are made on short notice and patients are followed closely by phone and in person until the surgery. Fructosamine levels are used to assess short term glycemic control as needed. To evaluate the pro-gram’s impact, records of initial 14 participants of the preoperative diabe-tes clinic were reviewed. Table 1 shows key characteristics of the studied cohort. Mean A1c before the preoperative diabetes clinic visit was 9.5%, reflecting poor glycemic control. After the intervention, mean fructosamine levels obtained preoperatively were comparable to A1c levels of < 7%, dem-onstrating significant improvement in glycemic control. Mean fasting glu-cose the day of surgery was 138mg/dL with no hypoglycemia. No periopera-tive complications occurred in any patient.

In conclusion, this innovative initiative resulted in significantly improved glycemic control preoperatively. Prospective studies are needed to confirm results.

Table 1.Sample characteristics (n=14) N or Mean (SD)Age 57 (10.14)Sex (Female/Male) 12 / 2Surgical Procedure (Ortho/other) 9 / 5Pre visit A1c % 9.50 (2.22)Fructosamine μmol/L (n=9) 282.22 (52.61)Time to Surgery (days) 45 (32.72)Glucose day of surgery (mg/dL) 138 (42.69)

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2441‑PUBValidation of an Insulin Infusion Nomogram for the Coronary ICUSEANN SETO, YVONNE KWAN, AMITA WOODS, Toronto, ON, Canada

Background: Hyperglycemia is associated with increased morbidity and mortality in acutely ill patients, including those treated in intensive care set-tings. However, there is evidence showing that intensive glycemic control is also associated with increased mortality as well as a higher incidence of severe hypoglycemia. Numerous studies have demonstrated that a stan-dardized insulin infusion nomogram improves the proportion of blood glucose levels within target range while reducing the risk of severe hypoglycemia. However, the majority of these trials studied medical-surgical intensive care unit (MSICU) patients and data on coronary ICU (CICU) patients is lacking.

Objective: To compare the efficacy and safety of standardized insulin infusion nomograms vs. non-standardized intravenous (IV) sliding scales in patients admitted to the coronary ICU.

Methods: A single-centre, retrospective before-after cohort study com-pared glycemic control in patients admitted to the CICU. Patients received regular IV insulin at rates specified by either non-standardized sliding scale (prior to May 2015) or standardized nomogram (May 2015 onward) titrated to a target range of 6-10 mmol/L (108-180 mg/dL).

Results: A total of 58 patients were enrolled into this pilot study. Patients in the nomogram group achieved a greater proportion of blood glucose levels within target range compared to patients in the IV sliding scale group (42.4% vs. 28.3%; P<0.001). The nomogram group also achieved the target blood glucose range more rapidly (15.4 hours vs. 25.8 hours; P=0.03). Hypoglycemia (0.15% vs. 0.86%) and severe hypoglycemia (0% vs. 0.10%) occurred less frequently in the nomogram group.

Conclusions: In patients admitted to the CICU requiring IV insulin, a stan-dardized insulin nomogram protocol resulted in a greater proportion of blood glucose levels being within the target range, while also decreasing the inci-dence of hypoglycemia.

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2443‑PUBGaps in Attendance in Young Adults with Type 1 Diabetes: Need for Quality ImprovementJENNY YUJING WANG, XINYE SERENA WANG, PATRIZIA DIRAIMO, CHERYL HARRIS-TAYLOR, LEAH J. DRAZEK, JANIS RUSEN, NICOLA A. FARNELL, KIS-HANI SARVANANTHAN, VICTOR CIPRIANO, LORRAINE L. LIPSCOMBE, GEETHA MUKERJI, Toronto, ON, Canada

Background: The transition from pediatric to adult type 1 diabetes (T1DM) care is associated with decreased medical follow-up, lost opportunities for counselling, and increased risk of diabetes-related hospitalizations.

Objective: We aimed to characterize attendance patterns and reduce non-attendance (no-show and cancellation within 24 hours) rates using the Model for Improvement quality improvement (QI) framework at a dedicated clinic for young adults (YA) with T1DM at the University of Toronto-affiliated Women’s College Hospital (WCH) in Toronto, Canada.

Method: Non-attendance rates between February 2015 and September 2016 were audited and plotted monthly on a Statistical Process Control (SPC) chart. Consecutive new patient charts from this period were reviewed for demographic data, metabolic control, and counselling rates. A patient survey was administered between October 2016 and January 2017 to iden-tify root causes of non-attendance. Continuous variables were reported as median (interquartile range) and categorical variables in percentages.

Results: There were 450 scheduled visits for 150 patients during this period; the mean non-attendance rate on SPC chart was 32% with no spe-cial cause variation. Chart review [n=30, 84% female, age 18.7 (18.2, 19.7), duration of T1DM 8 years (6, 14), and A1c 8.8% (8.0, 10.1)] showed 9.7% of referred patients were never seen, 18% were lost to follow-up, 39% were seen <3 times a year, and 74% had ≥1 non-attendance. Documented coun-selling rates for hypoglycemia, pre-conception, and sick day management were 68%, 68%, and 14%, respectively. In preliminary survey data (n=12), patients highlighted fear of judgment as cause for non-attendance and pre-ferred email reminders for appointments.

Conclusions: Non-attendance is a significant issue in the YA T1DM clinic at WCH. Using iterative Plan-Do-Study-Act cycles, a reminder system and patient-centered conversation guide will be tailored to address root causes of non-attendance and outcomes will be evaluated.

2444‑PUBThe Diabetes and Dementia (DIA‑DEM) Project: Targeting the For‑gotten PopulationAMAR PUTTANNA, KATELYN AITCHISON, PARIJAT DE, Birmingham, United Kingdom

The combined co-morbidity of diabetes and dementia is on the rise due to both an increase in the ageing population and prevalence of diabetes. The DIA-DEM project is aimed at assessing current trends in hospital admis-sions, diabetes medication usage and need, complications and length of stay with an overarching aim to reduce health and economic burden by optimis-ing care and minimising variation. We analysed a retrospective cohort of patients coded with ‘diabetes’ and ‘dementia’ admitted to a large district general hospital between June and August 2016. One hundred and forty one patients (73 male, 68 female, mean age 82.5 yrs +/- 4.2 SD) with type 2 dia-betes were included. Mean length of stay was 8.5 days (+/- 3.5 SD). Seven-teen (12.1%) had vascular dementia, 44 (31.2%) Alzheimer’s, 78 (55.3%) not coded. Fifty six (39.7%) were from a care home, 85 (60.3%) from their own home. Mean HbA1c was 55.6 mmol/mol (+/- 12.7 SD). Twenty five (17.7%) were on sulfonylureas, 28 (19.9%) on DPP-4 inhibitors, 63 (44.7%) were on metformin, 33 (23.4%) were on insulin, 25 (27.7%) were not on any medica-tion, 6 (4.3%) were on sulfonylurea and insulin and 11 (7.8%) were on 3 or more agents. Twenty six (18.4%) had at least one episode of hypoglycaemia, clinically significant (<3 mmol/l) in 15 (10.6%). Twenty (14.2%) patients died within 6 months, associated with HbA1c>55mmol/mol. Applying our DIA-DEM principles, 74 patients (52.5%) would have had focused diabetes inter-vention with medication adjustment (stopping SU or insulin where needed), timely HbA1c review that would allow appropriate management of glycae-mic abnormalities and help reduce length of hospital stay. This assessment of our DIA-DEM principles prove that much can be done in targeting this pop-ulation, particularly those on high doses of sulfonylurea and complex insulin regimes that increase the risk of hypoglycaemia and prolonged length of hospital stay. More data and targeted approaches are required to enhance care of this population and is part of the ongoing DIA-DEM project.

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2445‑PUBThe Value Index for SGLT2 Medications in Medicare PatientsSAAD SAKKAL, Mason, OH

Introduction: In the present paradigm, the yearly national expense for diabetes is $340 billion while less the 14% of people with Diabetes achieve all targets together. Medicare has an estimated 13520473 beneficiaries who have diabetes, with estimated annual costs of around $10 Billion ($9554829391). We asked in this abstract: What is the value index for pres-ent oral SLGT2 medications in Medicare patients?

Design: We compared the value index by finding how much money ($) is spent on improving HbA1c by 1% in three months. This calculation takes quality factor and cost factor for an estimate of the value of each medica-tion. We used the price Medicare pays for each from the Medicare spending data for 2015. We assumed SGLT2 will drop HbA1c by % 1.03 which is the best available in the literature.

Results: SGLT2: 1) annual costs per patient were (Invokana: $2097, Farxiga: 1739, Jardiance: 1467, and 1226 for Glyxambi, the latter is a combination) for an average annual cost per patient of $1998. 2) The total patients were 245458 and annual spending was $490595264. 3) Diabetes care value index: was calculated at $508 for Invokana, $422 for Farxiga, $356 for Jardiance, and $306 for Glyxambi. 4) Comparing The relative expense to Jardiance was 0.85 for Glyxambi, 1.18 for Farxiga and 1.42 for Invokana. 5) The observed direct annual price difference between the highest and the lowest priced medication was: $202 per patient, but, the actual effective difference based on the relative value index is $286. 6) If the annual cost difference of $286 per user is projected to all patients using the highest expense preparation (225029), the savings adds up to $64358294 or %13. 7) From the perspective of value index, it appears there are Two tiers: First is more clinically useful and economically effective (Jardiance/Glyxambi) and the second is higher priced (Invokana, Farxiga).

Conclusion: The effective value index saving of $286 favors the most economical preparation. A projection for the 225029 patients suggests a potential savings of $64358294.

2446‑PUBThe Value Index for DPP‑4 Medications in Medicare PatientsSAAD SAKKAL, Mason, OH

Introduction: In the present paradigm, the yearly national expense for dia-betes is $340 billion while less the 14% of people with Diabetes achieve all targets together. Medicare has an estimated 13520473 beneficiaries who have diabetes, with estimated annual costs of $10 Billion ($9554829391). We asked in this abstract: What is the value index for present oral DPP-4 medications in Medicare patients?

Hypothesis and Design: We compared the value index by finding how much money ($) is spent on improving HgA1c by 1% in three months. This calculation takes quality factor and cost factor for an estimate of the value of each medication. We used the price Medicare pays for each preparation from the Medicare spending data for 2015. We assumed DPP-4 will drop HgA1b by %0.66 which is the best available in the literature.

Results: DPP-4: 1) annual cost per patient were (Januvia: $2572, Ong-lyza: 2304, Tradjenta: 2105, Nesina: 1769) for an average annual cost per patient of $2447. 2) The total patients were 1197066 and annual spending was $2929750365. 3) Diabetes care value index: was calculated at $974 per 1% drop of HgA1c in three month for Januvia, $872 for Onglyza, $794 for Tradjenta, and $670 for Nesina. 4) Comparing the relative expense to Nesina was: 1.18 for Tradjenta, 1.3 for Onglyza and 1.45 for Januvia. 5) The observed direct annual price difference between the highest and the lowest priced medication was: $803 per patient, but, the actual effective difference based on the relative value index is $972. 6) If the annual cost difference of $972 per user is projected to patients using the highest expense DPP-4 preparations (943269), the savings adds to $916957468 or % 31. 7) From the perspective of value index, it appears there are Two tiers: First is most economical (Nesina), and the second is highest priced (Januvia, Onglyza).

Conclusion: The effective value index saving of $972 favors the most eco-nomical DPP-4 preparation. A projection for the 943269 patients suggests a potential savings of around $1 Billion per year ($916957468).

2447‑PUBThe Value‑Index Analysis of Metformin Preparations in Medicare Patients Could Save $100 MillionSAAD SAKKAL, Mason, OH

Introduction: In the present paradigm, the yearly national expense for dia-betes is $340 billion while less the 14% of people with diabetes achieve all targets together. A major part of the drop in adherence is medication pricing and side effects. We asked in this abstract: What is the value index for pres-ent oral Metformins in Medicare patients?

Design: We compared the value index by finding how much money ($) is spent on improving HgA1c by 1% in three months. This calculation takes quality factor and cost factor for an estimate of the value of each medica-tion. We used the price Medicare pays from the Medicare spending data for 2015. From the literature, we assumed %0.6 HgA1c drop for generic and %0,8 drop for non-generic.

Results: 1) Cost per unit (tablet or capsule) for generic metformin was: $0.07, for Metformin XR: $0.37, Glucophage: $1.37, for Glucophage XR: 1.05, Fortamet: $28.40, Glumetza: $39.1. 2) The annual Medicare expense per user was: generic $36.87, Metformin ER: $142, Glucophage: $747.8, Glucophage XR: $665. Fortamet: $12193, Glumetza $13915. 3) The diabetes care value index was: $20 per 1% HgA1c drop for generic, $55 for Metformin ER, $233 for Glucophage, $210 for Glucophage XR, $3810 for Fortamet, $4350 for Glu-metza. 4) From the perspective of value index, it appears there are three tiers: most economical (metformin and metformin ER), intermediate: 4-10 folds higher price (Glucophage and Glucophage XR) and the highest priced: 200 folds (Fortamet and Glumetza). 5) If the annual cost difference of $13000 per user (between Glumetza and Metformin) is projected to patients using the highest expense tier metformin preparations (10994), the savings could add up to $142922574 per year.

Conclusion: the value index for using metformin preparations in Medicare ($ spent to bring HgA1c by %1) still favors older agents over newer agents, with an annual difference of $13000. A projection for the 10994 patients using high expense preparations shows a potential savings of $142922574 per year.

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PEDIATRICS—OBESITY AND TYPE 2 DIABETES

2449‑PUB“Talking Was the Most Important Thing”JENNEY LEE, MARIT L. BOVBJERG, ROSA WOLFF, MICHAEL A. MAY, Corvallis, OR

Complex chronic diseases burden the healthcare system. Telehealth solutions might reduce that burden and improve health outcomes. There is concern that patients may be slow to adopt “cold technologies” in place of in-person interaction with healthcare providers. However, research on patients’ experiences with such technologies are sparse, leaving open the question of how telehealth platforms are perceived by healthcare consum-ers, or how readily they might be adopted by chronic disease patients.

This pilot study for Medicaid patients with diabetes employed a tablet-based health monitoring application. Patients used a cellular-enabled glu-cometer to upload blood glucose readings, which were monitored remotely by nurse case managers. Patients and nurses interacted via a text mes-saging feature and by phone. We conducted in-depth, semi-structured exit interviews (n=27) to assess patient experiences.

We found that, despite a relative lack of technological knowledge, patients held an overwhelmingly positive view of the intervention. The feature viewed most positively by the patients was the ability to send and receive text messages with the nurses. The tablet became an extension of the provider’s office, facilitating patients’ connection to healthcare profes-sionals. As one patient commented, “It was nice having that security there, that comfort of someone there caring about you.” The technology was not alienating; rather, the tablet became an important conduit for the nurse-patient relationship. Patients experienced the tablet-based application not as cold, but as imbued with emotionality. The perception of the tablet as a “warm technology” was key to patient satisfaction in this pilot project, and may prove a useful concept in adoption of future telehealth interventions.

PEDIATRICS—OBESITY AND TYPE 2 DIABETES

2450‑PUB“I Just Forgot”: Barriers and Strategies for Glucose‑Lowering Oral Medication Use and Impact on Adherence in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) TrialELIZABETH M. VENDITTI, PATRICE YASUDA, NANCY CHANG, LORI M. LAFFEL, GERALDINE H. MCGINLEY, NELLY MIRANDA, JEANIE B. TRYGGESTAD, NATALIE W. ABRAMSON, KENNY TAN, LINDA DELAHANTY, Pittsburgh, PA, Los Angeles, CA, Boston, MA, Philadelphia, PA, Houston, TX, Oklahoma City, OK, Aurora, CO, Rockville, MD

Youth with type 2 diabetes require lifelong medication use. Understand-ing individual adherence barriers and strategies for taking medications may aid in developing effective self-management interventions and preventing comorbidities. The aims of this analysis were to identify types and frequen-cies of barriers and strategies and their associations with baseline char-acteristics, and to explore whether strategies had an impact on adherence over time. Data from a subgroup of TODAY participants who maintained adequate glycemic control on any of the randomized study treatments [met-formin (M) alone, metformin + rosiglitazone (M+R), metformin + lifestyle (M+L)] at Months 6 (N=566), 12 (N=478) and 24 (N=376) following randomiza-tion were analyzed. The cohort was 64% female, 79% racial/ethnic minori-ties, mean age 14 years, <2 years diabetes duration, ≥85th percentile BMI, and had adult caregivers who agreed to provide support. Study clinicians documented the presence of medication barriers (e.g., disruptions to daily routines and other reported concerns) and strategies (e.g., rely on family, schedule, reminder device) to improve adherence. At each time point, suc-cessful medication adherence (≥ 80%) was inversely related to the number of barriers reported (p’s=.0001). “Forgetting” with no specific reason named, or disruptions in regular meals, sleep or schedule factors, accounted for ≥ 60% of responses. No significant baseline associations with barriers or adherence strategies were found. Family support was the strategy identified as helpful by most youth (≥50%), followed by the pairing of medications with daily routines (>40%); the latter was associated with higher adherence rates (p=0.009). These findings are similar to those reported in youth with other serious chronic diseases. Prospective studies to enhance family support and self-management are warranted.

Supported By: National Institute of Diabetes and Digestive and Kidney Dis-eases/National Institutes of Health (U01DK61212, U01DK61230, U01DK61239, U01DK61242, U01DK61254)

2451‑PUBAssociation between Iron Markers and Diabetes Risk in Indigenous Children Living at High AltitudeVALERIA HIRSCHLER, CLAUDIO GONZALEZ, CLAUDIA MOLINARI, GUSTAVO MACCALLINI, LUIS CASTANO, Buenos Aires, Argentina, Bilbao, Spain

Previous studies showed that iron overload induces the formation of free radicals and have deleterious effects on various cellular structures. We have previously found that Argentinean Indigenous children living at high altitude had higher haemoglobin levels than children living at sea level. The objective was to determine the association of four different markers of iron metabo-lism such as serum iron, ferritin, transferrin, and transferrin saturation with risk of type 2 diabetes in Indigenous children living at high altitude.

In a cross-sectional study, 352 school Indigenous children (166 males) liv-ing at 3750 m above sea level with a mean age of 9.64+2.33 years were examined in November 2012. Anthropometry, blood pressure, lipids, and glucose levels were measured. The prevalence of overweight was 7.7% (27) and obesity was 2.8% (10). Mean haemoglobin levels were 15.5g/dL. There were no significant differences in age, BMI, waist circumference, iron markers, and apo A and apo B levels between genders. Transferrin levels were positively associated with BMI (r0.24), glucose (r0.13), and apo B levels (r0.27); iron levels were inversely correlated with BMI (-0.13) and systolic blood pressure (r-0.13); and transferrin saturation was inversely associated with BMI (r-0.13), systolic blood pressure (r-0.15), TG/HDL-C (r-0.12), apo B (r-0.15), and HOMA-IR (r-0.14). Multiple linear regression analyses showed that transferrin levels were positively associated with age, BMI, and apo B levels adjusted for confounding variables (R2=0.15). Furthermore, transferrin saturation was inversely associated with BMI and apo B (R2=0.10).

High transferrin and low transferrin saturation were associated with dia-betes risk in Indigenous children living at high altitude with high iron levels. Our findings highlight the public health importance of monitoring iron mark-ers and also suggest that iron metabolism may contribute to future type 2 diabetes in this community.

2452‑PUBHigher Percent Body Fat in Infants of Diabetic Mothers vs. Healthy Term Infants in a Largely Hispanic PopulationELIA N. ESCANAME, RACHEL L. JACOB, CRISTINA PENON, DIANA ANZUETO, NICHOLAS ALANA, NICHOLAS CARR, JONATHAN KING, CYNTHIA BLANCO, San Antonio, TX

Background: Limited data on body composition in infants of diabetic mothers exists. Body composition early in life likely impacts later metabolic alterations.

Objective: Compare percent body fat (BF) in infants of diabetic mothers vs. healthy term infants, in a largely Hispanic population using anthropometric, air displacement plethysmography (Peapod) and dual-energy x-ray absorpti-ometry measures.

Design/Methods: Prospective longitudinal cohort of term singleton infants born to diabetic mothers control infants vs. control infants were assessed at birth and 3 months of age for anthropometric and skin fold measurements, air displacement plethysmography and DXA. Enrollment eli-gibility required no major congenital anomalies, no postnatal complications, AGA and no maternal chronic disease history in control infants. Statistical analyses were performed utilizing SPSS 22.0.

Results: To date, assessments of 38 healthy term infants born to moth-ers with and without diabetes mellitus had a mean percent BF of 13.5% ± 5.06% vs. 9.92% ± 3.95% vs. and fat mass 470 g ± 230 g vs. 310 g ± 139 g respectively that was significantly different (p=0.016, p=0.008) between the groups. Percent BF remained significantly higher after adjusting for pre-preg-nancy BMI and maternal age by logistic regression (OR=1.23, CI=1.01-1.51, p=0.03). Positive correlations were found between fat mass, arm circumfer-ence and thigh skin fold (R= 0.6, p<0.001) utilizing either Peapod or DXA.

Conclusions: Percent BF and fat body mass between term infants born to mothers with and without diabetes mellitus immediately after birth were higher in this cohort of primarily Hispanic mothers. Correlations between commonly used anthropometric measurements to estimate percent body fat are limited. Long term follow-up for body composition analysis with is ongo-ing. Methylation of key insulin signaling genes on cord blood samples from both groups are pending.

Supported By: San Antonio Medical Foundation

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PEDIATRICS—TYPE 1 DIABETES


2453‑PUBExperiences of Patients with Type 1 Diabetes during Transitioning to Adult CareSUSAN PENA-ALMAZAN, ADRIENNE STOLFI, PAUL BREYER, Dayton, OH

Transitioning to adult care by pediatric patients with type 1 diabetes (T1D) is a challenging task and there is limited information about the experiences of these patients during the transition process. This study aimed to obtain information from patients with T1D at Dayton Children’s Hospital Diabetes Clinic who transitioned to adult care.

Questionnaires were mailed to 102 patients who transitioned to adult care, with 33 (32%) patients responding. Mean (SD) age at diagnosis was 9.8 (4.1) y, and at transfer was 19.2 (1.1) y. Mean A1c prior to transfer, obtained from clinic charts, was 8.6% compared to self-reported mean A1c of 7.6% during the study. 39.4% of respondents were seen by an adult provider within 3 mo and 45.5% within 3-6 mo after transfer. Reasons for transfer included reaching 22 years old (n=11), leaving for college or work (n=9), feeling too old for children’s hospital (n=3), more convenient location for work (n=1), and pregnancy (n=1). Choice of current caregiver was dictated by referral from the pediatric provider, referral from relative or friend, convenient location for work or home, and the type of insurance provider. Adult endocrinologists followed 81.8% of respondents and 12.1% were followed as well by mental health providers. Twenty-five (75.8%) respondents recommended 18-22 y as the ideal age of transfer to adult care. 75.8% of respondents agreed that their pediatric provider was helpful in the transition process. Reasons cited included providing a list and information on adult endocrinologists, sending prompt referral and medical information to adult provider, and willingness to assist until transfer occurs. Respondents also gave suggestions to help ease transfer to adult care.

The experiences and impressions of the T1D patients in our clinic who transitioned to adult care gave valuable insight on the transition process. We have incorporated this information in the proposed transition program for our clinic and we will determine if these will help ease transitioning to adult care.

2454‑PUBGames for Children with Type 1 Diabetes: A Systematic ReviewBREE E. HOLTZ, KATHARINE M. MURRAY, MOLLY M. KAISER, East Lansing, MI

Background: More than half a million children under the age of 20 have type 1 diabetes (T1D). To ease the difficulties of management, video games have been tested to teach health skills, increase self-efficacy and improve adherence. The popularity of video games has led to the creation of seri-ous games to ease management of chronic diseases. The purpose of serious games is to focus on health management skills in an engaging and motivat-ing way.

Objective: The goal of this study was to review existing literature to deter-mine the impacts of serious games for children with T1D.

Methods: The search resulted in 4,929 articles. Of those articles, 157 were focused on diabetes. Studies were further trimmed based on their use of a game intervention, resulting in 7 articles that were assessed for this review.

The studies included a total of 352 participants with a mean of 50.29 (SD=47.29). Participant ages ranged from 3-38. Study duration varied from a 30-minute session in one study to 40 weeks in another. Only 3 were random-ized controlled trials.

Results: Four studies were usability tests, and 3 were randomized con-trolled trials. Study duration was varied, and 4 studies had a strict regime of play. Three studies found high comprehension, satisfaction, and enjoy-ment of the game. One found several usability and comprehension issues. The results were mixed for health and psychosocial variable outcomes. No significant health outcomes were found, and psychosocial variables were impactful in only 2 studies. No conclusion can be drawn between study duration and significant findings. Strict regime of play did not appear to impact significant outcomes.

Conclusion: This study reports the results of 7 studies that tested impacts of a video game on children with T1D. Unlike previous systematic review findings, positive outcomes in satisfaction, health or psychosocial variables were not found to be more frequent among studies that had a longer dura-tion. This review provides important implications for future development of games for the management of T1D.

2455‑PUBThe Development and Prototype Testing of a Patient‑Centered mHealth App for DiabetesBREE E. HOLTZ, KATHARINE M. MURRAY, DENISE S. HERSHEY, JULIE K. DUN-NEBACK, SHELIA R. COTTEN, AMANDA J. HOLMSTROM, ARPITA VYAS, MOLLY M. KAISER, MICHAEL A. WOOD, East Lansing, MI, Lansing, MI, Lubbock, TX, Ann Arbor, MI

Background: Type 1 diabetes (T1D) afflicts more than half a million chil-dren. T1D is complex and parents often manage their child’s disease. Chil-dren must eventually transition to self-care, which is often difficult. Adher-ence to the prescribed treatment regimen drops during this time.

Mobile health (mHealth) apps have been shown to be successful at moni-toring and managing diabetes. Our proposed app, MyT1DHero is unique in that it links the child’s information to their parent’s cell phone and promotes positive communication within families.

Objective: The purpose of this study was to a use patient-centered approach to inform the development of our app, MyT1DHero. We also con-ducted prototype testing of the app with our target population to measure usability and satisfaction.

Methods/Development Process: Conceptualization of the app included brainstorming sessions with 4 clinicians specializing in T1D and communi-cation experts. We conducted qualitative focus groups with kids with T1D and their parents to learn about their management plan and communication patterns, what apps they use, and feedback on our app. Results drove the design and development of the app, created by a professional app devel-opment company. Prototype testing was conducted in winter 2016. We recruited 10 parent/child pairs (n=20) to use the app for 4 weeks. Interviews measured satisfaction of app usage. Server information was analyzed to quantify learning time, efficiency of use, engagement and user errors.

Results: Prototype testing participants were satisfied with the app. There were a few minor issues that were addressed. These findings informed app refinement for use in the full intervention. Recruitment for that study is underway now.

Conclusions and Future Implications: Gathering insight from clinicians and patients about daily management of T1D supports the development of this app to aid in the transition to self-management. The results of prototype testing show promising impacts that we hope to see in intervention testing.

Supported By: American Diabetes Association (1-16-ICTS-045 to B.E.H.)

2456‑PUBCorrelation of Proinsulin to C‑Peptide Ratio with BMI and Age in Children with Type 1 DiabetesDANIEL S. HSIA, BENJAMIN R. ELLISON, JEFFREY H. BURTON, Baton Rouge, LA, Waco, TX

The proinsulin to C-peptide (PI:C) ratio has been proposed as a marker of β-cell dysfunction. Elevations in the PI:C ratio are seen in people at risk for and diagnosed with type 1 and type 2 diabetes while reductions in the PI:C ratio have been associated with improved β-cell function. Nine participants with a mean age of 13 years, a mean BMI of 21 kg/m2, and within 5 years of type 1 diabetes diagnosis were enrolled in a single visit cross sectional study. Their mean HbA1c was 8.5% (69 mmol/mol). Ten participants with a mean age of 13 years and a mean BMI of 25 kg/m2 were enrolled as a control group. PI and C levels were measured concurrently after a 10 hour fast with levels below the assay lower limit of detection assigned a value of one-half the lower limit of detection. Molar ratios of PI and C were calculated and multiplied by 100 to obtain PI:C ratios. PI:C ratios were significantly differ-ent between the type 1 diabetes and control groups (6.56 vs. 1.46, p< 0.01). A negative correlation was seen between the PI:C ratio and BMI (r2= 0.63; p= 0.01) as well as between the PI:C ratio and age (r2= 0.45; p= 0.05) in the type 1 diabetes group (Figure). These relationships were not observed in the control group. These results indicate that children with type 1 diabetes and a higher BMI may have less β-cell dysfunction (lower PI:C ratio) and that chil-dren diagnosed at a younger age may have more β-cell dysfunction (higher PI:C ratio) compared to older children.

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Figure.

Supported By: Pennington Biomedical Research Foundation; National Institute of General Medical Sciences (1U54GM104940); Nutrition Obesity Research Cen-ters (P30DK072476); Eunice Kennedy Shriver National Institute of Child Health and Human Development (1UG1HD090967 to D.S.H.)

2457‑PUBThe Efficacy of Pediatric Outreach Diabetes Clinics vs. Central Dia‑betes Clinics: A Retrospective Chart Review StudyROB LINDSAY, DANIA AL-HAMAD, Salt Lake City, UT

Little has been reported about the efficacy of pediatric outreach (OR) diabetes clinics in general, and more specifically in pediatrics. Primary Chil-dren’s Hospital provides care to children from 6 states in addition to Utah and has had an OR program since 1982. This study compares one provider’s patients’ Hemoglobin A1c levels from OR and the central clinic over the past 8 years to assess the quality of care provided to these distant patients. Inter-estingly, there was no significant difference between any of the groups, con-sidering that the central patients had access to clinic social workers, more flexibility in scheduling and rescheduling and more opportunity to meet with diabetes educators and dietitians between visits. This study shows that dia-betes control tends to be similar in OR and central settings.

Table. Male Diabetes Patients Hemoglobin A1C Central Clinics vs. OR (n=Number of Encounter).

Central ORAge n A1C% n A1C%</=7Y 508 7.9 546 8.18-11Y 738 8.1 746 8.012-15Y 1147 8.8 994 8.616-18Y 680 8.5 667 8.6Total 3073 8.4 2953 8.3

Table. Female Diabetes Patients Hemoglobin A1C Central Clinics vs. OR (n=Number of Encounter).

Central ORAge n A1C% n A1C%</=7Y 415 7.9 428 7.98-11Y 644 8.0 640 8.212-15Y 953 8.5 709 8.716-18Y 684 8.3 457 8.2Total 2696 8.2 2236 8.3

2458‑PUBEffect of Linagliptin Added to Insulin Treatment on Metabolic Con‑trol, Insulin Dose, and Hypoglycemia in Patients with Uncontrolled Type 1 DiabetesMARIA L. MONTES DE OCA LOYOLA, CLAUDIA M. HERNÁNDEZ-ROBLES, EDGAR DURAN PEREZ, ALBERTO AGUILAR GARCÍA, MARÍA L. EVIA-VIZCARRA, EDEL R. RODEA-MONTERO, DIANA FARFÁN VÁZQUEZ, ANA K. VILLA-MARTÍNEZ, GEOR-GINA A. BARAJAS-MEDINA, FABIOLA ANGULO-ROMERO, MARÍA DE LOURDES REYES-ESCOGIDO, RODOLFO GUARDADO MENDOZA, León, Mexico

Introduction: T1DM is characterized by autoimmune destruction of the pancreatic beta cells, and treatment is based on insulin. New studies have shown abnormalities in glucagon and incretin effect in T1DM. The goal of this study was to evaluate the effect of Linagliptin + insulin on metabolic control, insulin dose and hypoglycemia in uncontrolled type 1 diabetic patients.

Methods: This was single group study, including adult patients with uncon-trolled type 1 diabetes (HbA1c higher than 7%). The protocol was approved by the ethical committee. Patients were recruited from the Endocrinology Department, and they had a basal evaluation with HbA1c measurement, lipid profile, and body composition, as well as register of insulin dose, pre- and post-meal capillary glucose, and frequency of hypoglycemia. After this, Lina-gliptin was started at dose of 5mg every 24 h during 3 months. Patients had a monthly follow-up visit and the adjustment of insulin dose was performed by a blinded Endocrinologist. At 3 months, all the basal measurements were repeated. Data were analyzed with a paired t test (p less than 0.05).

Results: Seven patients were included in the study but only 5 (4 female and 1 male) completed the 3 months follow-up. The patient´s average age and duration of the disease were 21 ± 6 and 9.6 ± 5.5 years, respectively. There was a decrease in HbA1c (10.2 ± 1.9 vs. 9.3 ± 0.3%, p 0.257), pre-meal glucose (169.3 ± 16.7 vs. 154.6 ± 0.4 mg/dl, p 0.427), post-meal glucose (174.8 ± 13.3 vs. 155.3 ± 13.9 mg/dl, p 0.014), insulin dose (40.6 ± 9 vs. 36.6 ± 13.3 IU, p 0.036), and frequency of pre and post-meal hypoglycemia (3 vs. 2, and 2 vs. less than 1 per month, respectively, p 0.215).

Conclusion: Linagliptin added to insulin scheme improved metabolic con-trol and reduced the frequency of hypoglycemia; DPP-IV inhibitors and other oral therapies should be more evaluated to define the role they may have as a complementary treatment to insulin in uncontrolled patients with type 1 diabetes.

Supported By: Hospital Regional de Alta Especialidad del Bajio, León, Guana-juato, México

2459‑PUBFifty Shades of Transferring Pediatric Diabetes Patients to Adult CareSARA MOASSESFAR, SALEH ADI, STEPHEN E. GITELMAN, MEGUMI OKUMURA, MARCELA ARREGUI REYES, San Francisco, CA

Background: Studies show youth “graduating” out of pediatric diabetes (DM) care have delayed follow-up in adult clinics. To counter this, our pedi-atric DM center developed a transition program to prepare patients for self-management and help establish adult care. No study has explored reasons why young adults transfer out of pediatric care, thus we sought to explore these and the prevalence of establishing adult care.

Methods: We compared 2 groups of adults transferring out of our care in the past 3 yrs. Group 1 preceded our transition program (n=21) and Group 2 was enrolled in it (n=36). We phoned patients to ask a) had they estab-lished adult DM care with >1 visit within 1 yr of transfer, b) if yes, when and where, c) if no, why not and d) reasons for transfer. Nonresponders and those responding but not in adult care were recontacted in 3 mos and left up to 2 messages. Descriptive statistics and t-tests were performed on base-line characteristics and outcomes.

Results: Baseline characteristics were similar between groups. In the combined cohort, age was 18-28 yrs (mean 20.6); 49% was female; 81% Caucasian; 33% publicly insured; 90% had T1D; 10% T2D, CFRD or MODY; mean DM duration was 11 yrs; and mean HbA1c was 9.0%. For Group 1, 7/21 patients (33%) responded, of which 6 (85.7%) had established adult care within 1 yr of transfer. For Group 2, 18/36 responded, of which 13 (72%) had established adult care and 4 (22%) were in the process. Time from last pediatric to 1st adult visit was 3-12 mos. Patients not in adult care did not dis-close why. Reasons for transfer were similar between groups and included residential changes (59%), insurance changes (25%) and desiring adult care (7%).

Conclusion: Main reasons for transfer were location and insurance, rather than desiring adult care. Both groups had suboptimal response rates, highlighting challenges in following transfer patients. However, the group

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involved in our transition program had higher rates of responding, sharing clinical information, and establishing adult care or being in the process.

Supported By: National Institutes of Health (K12DK094726)

2460‑PUBDiabetes Management Difficulties and Strategies in Children with Autism Spectrum Disorder and Type 1 DiabetesKELLY STANEK, ERIN YOUNGKIN, JENNIFER K. RAYMOND, SHIDEH MAJIDI, Aurora, CO, Los Angeles, CA

Patients with Autism Spectrum Disorder and type 1 diabetes (ASD+T1D) may encounter unique difficulties managing T1D and distinct strategies may improve T1D care. A questionnaire on independent tasks, difficulties, and strategies in T1D management was given to caregivers of patients with ASD+T1D (n=13) and a control group of T1D patients without ASD (n=39) matched for age, sex (92% male), race/ethnicity, and T1D duration. More ASD+T1D caregivers indicated their child could not complete any T1D care task independently (30.8% ASD+T1D vs. 0% T1D). Both groups ranked spe-cific difficulties from most to least difficult. Change in diet (46% vs. 44%) followed by carb counting (24% vs. 31%) were the 2 most difficult tasks in ASD+T1D and T1D cohorts. Less than half of the ASD+T1D group (46.2%) had a strategy to overcome difficulties, compared to 87.2% of controls. Both groups selected insulin pump as the most useful strategy (23.1% ASD+T1D vs. 46.2% T1D). ASD+T1D families preferred using schedules (23.1%) while T1D families used reminders (43.6%). Overall, controls appeared to have greater ability to perform diabetes care tasks independently and have strategies to overcome difficulties in management. Although some with ASD +T1D may be unable to gain complete independence, development and discussion of strategies to overcome difficulties may be helpful for T1D man-agement in patients with ASD+T1D.

Table.ASD+T1D Control

Age 12.62 ± 0.88, n=13

12.41 ± 0.46, n=39

Independent TasksCheck BG independentlyCount Carb independentlyInsulin DosingGive Insulin independently

9 (69.2%)4 (30.8%)5 (38.5%)6 (46.2%)

39 (100.0%)29 (74.4%)22 (56.4%)17 (43.6%)

Presence of StrategyNumber of Strategies to overcome difficulties

6 (46.2%)0.85 ± 0.27

34 (87.2%)1.44 ± 0.13

2461‑PUBParental Views on Transitioning to Adult Management in Patients with Autism Spectrum Disorder and Type 1 DiabetesSHIDEH MAJIDI, KELLY STANEK, ERIN YOUNGKIN, JENNIFER K. RAYMOND, Aurora, CO, Los Angeles, CA

Transferring to adult diabetes care is a challenge for patients with type 1 diabetes (T1D) and may be more difficult for those with Autism Spectrum Disorder (ASD) and T1D. Resources for patients with Autism Spectrum Dis-order and type 1 diabetes (ASD+T1D) transitioning from pediatric to adult providers are lacking. Via a questionnaire completed by caregivers, our study examined views and comfort with transitioning in those with ASD+T1D ≥12 years of age (n=6) compared to a control group of T1D patients (n=28). The average age of ASD+T1D patients was 15.5 years (range 13-17 years) vs. 15.2 years (range 12-18; one patient 12 years). Both groups believed transi-tion should occur at an average of 18.5 years. More families with ASD+T1D had started thinking or creating a transition plan (66.7% ASD+T1D vs. 42.9% T1D), and few providers had discussed transitioning with families (16.7% ASD+T1D; 14.3% T1D). Both ASD+T1D and T1D families wanted a provider to discuss a plan with them (100%; 70.9%). Families with ASD+T1D feel less confident about receiving adequate information and tools for transitioning (66.7% ASD+T1D very or somewhat confident vs. 85.8% T1D). ASD+T1D families were most concerned about switching care facilities and less per-sonal interaction when transitioning to adult care, while T1D families were most concerned about their child’s medical response to change in care (i.e., changes in A1c level and self-management). Overall, we found additional guidance regarding transition for all patients with T1D is needed. Those with a comorbid condition may start formulating a transition plan at a younger age, indicating that diabetes providers should initiate transition conversa-tions earlier for those with additional diagnoses, such as ASD. Larger studies may help determine the specific resources needed.

2462‑PUBConstruction of a Diabetes Well‑Being Survey for Teens with Type 1 Diabetes (T1D)BARBARA J. ANDERSON, CHARLOTTE COHEN, WENDY LEVY, DEMET OZKAYA, THOMAS DANNE, LORI M. LAFFEL, Houston, TX, Boston, MA, Paris, France, Hannover, Germany

Objectives: Although teens with T1D are vulnerable to depression, dia-betes distress and reduced quality of life, no single brief measure assesses their diabetes well-being.

Methods: An international multidisciplinary panel (peds, endos, psycholo-gists, RNs/RDs) informed design of a well-being survey for teens with T1D. The survey, including a 5-point Likert response scale, had 6 domains, each with 2 positive and 2 negative items: self-worth; diabetes distress/worry; communication; social/peer integration; weight/body image; and family. To assess clarity and acceptability of the 24-item survey and to identify 12 pre-ferred items (2 for each domain), 18 younger (13-15 yrs) and 18 older teens (16-18 yrs) with wide ranging A1c values (<7->10%) completed the survey (completion time 5-10 min) and then responded to a standardized cognitive interview by trained research staff at 2 U.S. diabetes centers. Interviews were audio-recorded and analyzed for common themes about clarity, accept-ability and item preference.

Results: Teens (50% male) had mean age 16, T1D duration 10 yrs; most were pump-treated. There was strong consensus that items about weight and peer relations were not relevant or acceptable, whereas items about family interactions, motivation and support for T1D self-care were most important. Teens preferred positively to negatively worded items and reported feeling comfortable sharing responses with their healthcare teams to benefit clinical interactions and inform recommendations. In response to a strong preference for items about family, motivation and support, we cre-ated a revised 12-item well-being survey reflecting teen recommendations.

Conclusions: While teens struggle to attain A1c targets, assessing teen well-being may offer opportunities to intervene on modifiable family factors related to provision of family support and motivation for self-care. A valid and reliable survey of teen diabetes well-being emphasizing family issues may yield an important patient-reported outcome.


2463‑PUBEasing the Transition: A Program for College‑Bound Teens with DiabetesJULIE M. SURHIGH, DAVID P. TOBIN, Royal Oak, MI, Rochester, MI

Background: This study aimed to evaluate the effectiveness of a pre-college education program at improving knowledge, self-care skills and glycemic control in graduating high school seniors with type 1 diabetes. A one-time education program was piloted by our division in May 2015.

Subjects and Methods: 60 high school seniors with diabetes were invited to attend. The program consisted of a lecture followed by a discussion fea-turing a panel of college students with type 1 diabetes. Educational curricu-lum was adapted from the American Association of Diabetes Educators’ 7 Self-Care Behaviors. Participants completed a pre-class quiz, an immediate post-class quiz, and a 1-year follow-up quiz. Of the 60 students invited, 12 attended the program and 7 completed the follow-up quiz at 1 year and were enrolled in the study.

Results: Of the 7 high school seniors enrolled in the study, 57.1% used insulin injection therapy and 42.9% used insulin pump therapy. Mean HbA1c was 8.04±0.92%. There was a significant improvement in mean quiz score after attending the program (P=0.0113), with an average improvement in score of 2.14±1.57 points (maximum score 20 points). Significant improve-ment in mean quiz score was maintained at one year (P=0.0353), with an average improvement in score of 1.43±1.40 points. Quiz questions most frequently missed prior to the program included topics on alcohol consump-tion, mental health, and understanding how a correction factor works. There was no significant change in HbA1c values between baseline and one-year follow-up.

Conclusions: Our data suggest that knowledge gaps exist in specific areas of diabetes self-care unique to young adults transitioning to college. A one-time education program offered to graduating high school seniors appears to improve short- and long-term knowledge of diabetes self-care. Glycemic control was not significantly altered; however, further investigation utilizing a control group would help to better elucidate the impact of the program.

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2464‑PUBProfessional Continuous Glucose Monitoring before Starting Insu‑lin Pump TherapyJESSICA A. FERRIS, ROSHANAK MONZAVI, Los Angeles, CA

When patients with type 1 diabetes (T1D) transition from a multiple daily injection regimen to insulin pump, glycemic control may initially worsen until optimal doses are found. Continuous glucose monitoring (CGM) provides detailed blood glucose (BG) data, which can be used to personalize starting pump insulin doses. We conducted a randomized controlled pilot study using Medtronic iPro2 CGM for insulin dose determination at pump initiation in T1D youth to assess whether its use would improve time within target BG (70-180 mg/dL). Ten subjects aged 4-16 years with T1D for ≥3 months, naïve to CGM, and starting on insulin pump were recruited. All subjects wore the CGM for 5 days at ~2 weeks before, initial week, and 6 weeks after pump start. In the intervention group (INT), CGM data was used to determine insu-lin pump doses. Subjects were 10.6±3.8 years old and had T1D for 2.5±3.5 years. No differences were noted between groups at baseline: % time in target BG (63.2 vs. 63.5%), mean BG (173 vs. 167 mg/dL), and MAGE (108 vs. 90.5 mg/dL) for INT vs. control group, respectively. Preliminary data showed a trend towards improved glycemic control in INT and worsened control in the control group. Differences between groups were not statistically sig-nificant, most likely due to insufficient power. Using professional CGM prior to insulin pump appears to improve glycemic control and decrease glycemic variability during transition to pump therapy.

Table.Intervention

GroupControl Group

% time in target - 5 days 71±8.2 57.5±10% time in target - 6 weeks 81.7±13 53.5±13Mean BG (mg/dL) - 5 days 146±20 167±25Mean BG (mg/dL) - 6 weeks 137±6.6 203±71Mean Amplitude of Glycemic Excursion (mg/dL) - 5 days 93.1±26 102±30Mean Amplitude of Glycemic Excursion (mg/dL) - 6 weeks 61.5±7.0 127±14

Supported By: Medtronic; Children’s Hospital Los Angeles

2465‑PUBPercentage of Type 1 Diabetes for Children and Adolescents in Tai‑wan: A Nationwide DataYI DER JIANG, SHIN YU LIEN, Taipei, Taiwan, Taoyuan, Taiwan

Background: The urine screening program for nearly 3 million schoolchil-dren was the first nationwide data that type 2 diabetes was predominant for schoolchildren but limited by 38% with unknown type. We tried National Health Insurance (NHI) data to demonstrate the percentage of type 1 diabe-tes aged 5 to 19 y/o instead.

Methods: The case number of ICD-9-CM code 250, the combination of type 1 and type 2 diabetes, in either inpatient or outpatient diagnosis, was the official data announced annually by Ministry of Health and Welfare in Taiwan, together with that of NHI insured population. Type 1 diabetes was based on the issue of the Catastrophic Illness Certificate from NHI with the same code. In addition of NHI coverage rate, the percentage of type 1 dia-betes among schoolchildren 5~19 years of age can be shown from 2003 to 2010, and stratified by gender and 5-year age groups.

Results: The NHI coverage rate varied between 97% and 98.4%, high enough for a nationwide data. The percentage of type 1 diabetes ranged from 26% to 29.9% with mean value of 28.1% from 2003 to 2010. It was higher for girls (30.9%) than that for boys (25.6%) in each age group, and negatively associated with age for both gender.

Conclusion: In urine screening program, type 1 diabetes (n=78) accounted for 13.4% of all schoolchildren diabetes (n=581), and 21.6% after exclud-ing 230 unknown type or without physician’s diagnosis of diabetes. If only type 1 and type 2 (n=257) diabetes included, type 1 diabetes accounted for 23.3%, very close to 26.0 ~ 29.9% in this study, but much lower than over 90% in western countries. Such a marked difference may come from low incidence of type 1 diabetes and high prevalence of impaired fasting glucose (IFG). Incidence of type 1 diabetes in Asia was no more than 5, much lower than 10~65 per 100,000 in western countries. IFG for adolescents was 22% in Taiwan, and correlated to male, obesity, high blood pressure, high triglyc-eride or low HDL. An intervention program must be designed for boys to prevent type 2 diabetes.

Supported By: Taiwan Ministry of Science and Technology

2466‑PUBChanging Profile of GAD and IA‑2 Antibody Positivity in Recently Diagnosed Type 1 Diabetes Indian ChildrenSUDIP CHATTERJEE, DEBMALYA SANYAL, SANDIP K. BATABYAL, SUBRATA MAITY, Kolkata, India

Objective: Existing evidence on type 1 diabetes (T1D) patients from India proposes that fairly large number are negative to GAD 65 (Glutamic Acid Decarboxylase) and IA-2 (Insulinoma Antigen 2) auto antibodies. Socio-eco-nomic factors and enterobiome changes are well known to alter antibody positivity rates. We wanted to see whether there were secular changes in antibody positivity rates among newly diagnosed T1D children in response to rapid transition in Indian lifestyle.

Methods: All newly diagnosed T1D patients aged less than 16 years had GAD and IA-2 antibodies measured between 2007 and 31st August 2016.

Results: The chi-square test for trend analysis showed a significant rising trend for IA2 antibody alone positive (p<0.001, chi-square for trend=17.437, df=1) and either antibody positive percentages (p<0.001, chi-square for trend=22.71, df=1), but not in the GAD antibody positivity (p=0.059, chi-square for trend=3.567, df=1) and in dual antibody positive percentages (p=0.486, chi-square for trend=0.485, df=1) over a period of ten years i.e., from 2007 to 2016.

Conclusion: There is a substantial change in the antibody positivity rates in newly diagnosed T1D children over the last nine years. We postulate the increase in autoimmunity is attributed to the changes in the enterobiome, obesity (BMI), hygiene, socioeconomic development and exposure to oral polio vaccine. This rise in autoimmunity may also be a significant contribut-ing factor towards the recent increased incidence of T1D in India.

2467‑PUBDisordered Eating Develops Early in Adolescents with Type 1 Dia‑betesLISAL J. FOLSOM, TAMARA S. HANNON, Indianapolis, IN

Background: There is an increased incidence of both disordered eating behaviors (DEB) and eating disorders (ED) in adolescents with T1D. Patients with T1D and concurrent DEB or ED have more medical complications and a tripled mortality rate. There would be great benefit in determining risk fac-tors for DEB and ED, and intervening before these harmful behaviors arise.

Objectives: To establish the course of eating behaviors in adolescents with newly diagnosed T1D (NDT1D) and determine if change in these behav-iors negatively affects glycemic control.

Methods: Subjects with NDT1D were followed prospectively for 6 months after diagnosis. BMI and HbA1c were obtained at each visit. Validated ques-tionnaires and online dietary recall software were used to measure eating behaviors and nutrition knowledge. Descriptive statistics, student’s t-tests, and regression analyses were used for analysis.

Results: Twenty-five patients with NDT1D participated. Age ranged from 10-18 years. HbA1c was 13.5 ± 2.2% at diagnosis, and 6.8 ± 1.2% at 6 months (p<0.01). Average BMI increased by 2.6 ± 0.8 kg/m2 (p<0.01). Reported intake of total calories, carbohydrate, sugar, fat and protein did not change, however nutrition knowledge significantly increased (p=0.05). Female subjects were more likely to screen positively for DEB than males at 6 months (p=0.02). Positive screening for DEB correlated with a higher HbA1c at 6 months (p=0.03, R2=0.24).

Conclusion: Although nutrition knowledge increased, dietary composi-tion did not change. Positive screening for DEB was associated with higher HbA1c. This finding supports the hypothesis that patients with DEB have poorer glycemic control, and suggests this trend manifests as early as 6 months after diagnosis. Our results indicate that targeted nutrition educa-tion is critical in T1D, as reported dietary intake did not change despite nutri-tion education. They also highlight the need for interventions that translate nutrition knowledge into practical methods that adolescents will embrace.

Supported By: National Institutes of Health (2T32DK065549)

2468‑PUBDoes Iron Status Explain Racial Disparity in Mean Blood Glucose (MBG) Independent of HbA1c Outcome for Children with Type 1 DM (T1D)?MAHMOUD A.A. HAMDAN, STUART CHALEW, New Orleans, LA

Introduction: Blacks (B) have higher HbA1c than whites (W) independent of differences in MBG and RDW-CV. Decreased iron status is associated with increased HbA1c. Thus low iron may account for higher HbA1c.

Methods: We evaluated iron status in a mixed race sample of youth with T1D. Labs were obtained for ferritin, soluble transferrin receptor (sTfR),

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HbA1c and CBC. MBG was derived from glucose meter records over last 30 days. Statistical analysis was done by t-test and multiple variable analysis.

Results: Comparison of variables between groups by t-test presented in Table. HbA1c and MBG were higher in B than W. Ferritin was correlated with Hb but not HbA1c or MBG. Differences in ferritin and sTfR between the groups were not significant. WBC and platelet levels were not differ-ent between groups. In multiple variable analysis race (p=0.0241) and MBG (p=0.0042) were statistically influential on HbA1c, r2=0.34, p=0.0002. Fe, sTfR or ratio were not statistically significant when added to the model.

Conclusion: After adjustment for race and MBG, iron indices were not independent predictors of HbA1c levels. These observations indicate that factors besides iron status contribute to MBG-independent racial disparity in HbA1c between B and W pediatric patients.

Supported By: Endocrine Fellows Foundation

2469‑PUBOral Administration of Lactobacillus Reuteri Improves Periodontal Disease in Children and Adolescents with Type 1 DiabetesBARBARA PREDIERI, SARA BARBIERI, DALILA MICELI, CHIARA CATTELANI, SILVIA MAZZONI, ANDREA FORABOSCO, LORENZO IUGHETTI, Modena, Italy

Objectives: There is disagreement on the effect of diabetes on oral hygiene. Probiotics creating a biofilm could protect the oral tissues against periodontal bacteria. We aimed to assess the effects of Lactobacillus reuteri administration upon the oral health of children and adolescents with type 1 diabetes (T1D).

Methods: Forty-three patients (11.3±2.77 yrs.; T1D duration 58.2±38.0 months) were enrolled and randomly assigned to Group A (probiotic - 10^8 CFU/day for 3 months) and Group B (no probiotic). Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), insulin dose (IU/kg/day), and HbA1c were measured at baseline (T0) and 3-months after (T1).

Results: FMPS significantly improved in both Group A and B (p<0.05). In Group B insulin dose increased (p=0.01) and HbA1c improved (p<0.001) at T1; in Group A the metabolic control was unchanged. In Group A, 13 out 22 patients reported a regular probiotic intake (Group A1), while the other ones used it sporadically (Group A2). Despite FMPS and FMBS values were not different between groups at T0, they were significantly lower (p<0.05) in Group A1 respect to Group A2 at T1 and longitudinally decreased in Group A1 but not in Group A2 (Table).

Conclusions: Our preliminary data suggest that 3-months administration of probiotic might improve the oral health of children and adolescents with T1D and confirm the influence of the glycemic control.

Table. Data are Reported as Mean ± SD (Median).Group A1 Group A2 p

T0FMPS (%) 88.8 ± 11.2 (90.0) 92.8 ± 12.5 (100.0) 0.367FMBS (%) 64.6 ± 28.7 (60.0) 78.3 ± 24.1 (80.0) 0.317

T1FMPS (%) 70.0 ± 27.1 (80.0)

p=0.017 vs. T086.1 ± 27.5 (100.0)

p=0.465 vs. T00.038

FMBS (%) 49.6 ± 23.7 (50.0)p=0.074 vs. T0

78.9 ± 28.4 (95.0)p=0.787 vs. T0

0.025

2470‑PUBReal‑Life Data: Insulin Tregludec in Children and Young Adults with T1DMNEHAMA ZUCKERMAN-LEVIN, SHALEV ZUCKERMAN, NAIM SHEHADEH, Haifa, Israel

Achieving good glycemic control is a major goal in T1DM. This includes striving for a target HbA1c, weight adjusted insulin dosing, minimizing hypo-glycemic episodes, and decreasing blood glucose variability. Tregludec is a

new long acting insulin associated with low blood glucose variability. Real life data in adults with T1DM and T2DM demonstrated significant reductions in HbA1c, hypoglycemic episodes, and insulin dose. Our aim was to evalu-ate glycemic control following switching to Tregludec in children and young adults. We included patients <31 years diagnosed with T1DM with HbA1c >7.5 who were switched to Tregludec. HbA1c was measured at baseline and 3-6 months after the switch. The primary end point was change in HbA1c. Dose of basal and total insulin (IU/kg body weight/day) were calculated. Self-monitoring of blood glucose measurements were documented two weeks before and 3 months after the switch. 90 patients (56% girls, age range 2.9-31 years, mean 14±5.4 years) were included. Mean duration of T1DM was 5.5±4.8 years. Previous basal insulin treatments were Lantus (68%), Levemir (25%), Toujeo (1.9%), or CSII (5.1%). Mean HbA1c at baseline was 9.04±1.7. After 3 months of Tregludec treatment mean HbA1c decreased to 8.47±1.6 (p<0.0001). After 6 months it decreased further to 8.23±1.3 (p<0.02). Mean basal and total insulin dose at baseline were 0.38±0.17 IU/kg/day and 0.87±0.32 IU/kg/day, respectively. After 3 months of Tregludec treat-ment mean basal and total insulin dose decreased to 0.35±0.13 IU/kg/day and 0.76±0.23 IU/kg/day (p<0.0001, p<0. 01), respectively. After 3 months mean glucose measurements decreased from 204.6±68.5 to 189.7±61 mg/dl (p<0.03) and the percent of patients with very high (>300 mg/dl) and very low (<50 mg/dl) glucose levels decreased significantly (p<0.015, and p<0.017, respectively). Less hypoglycemic episodes were observed after the switch. These results demonstrate that switching to Tregludec as basal insulin in children and young adults with T1DM improves glycemic control.


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2472‑PUBBone Turnover in Women with Prior Gestational Diabetes Mellitus Before and After 52 Weeks’ Treatment with LiraglutideLOUISE VEDTOFTE, ELISABETH HANNERUP, SIGNE FOGHSGAARD, THORA BUHL, ELISABETH R. MATHIESEN, JENS A. SVARE, TINE D. CLAUSEN, PETER DAMM, NIKLAS R. JØRGENSEN, FILIP K. KNOP, TINA VILSBØLL, Hellerup, Denmark, Copenhagen, Denmark, Herlev, Denmark, Hillerød, Denmark

Liraglutide induces weight loss and as weight loss is associated with loss of bone mass, we investigated the effect of liraglutide-treatment in women with prior gestational diabetes mellitus (pGDM) on whole-body bone mineral density (BMD), whole-body bone mineral content (BMC), the bone resorption marker C-terminal telopeptide of type 1 collagen (CTX-I) and the bone for-mation marker procollagen type 1 amino-terminal propeptide (P1NP). One-hundred and two women with pGDM (age: 38±5 years (mean±SD), BMI: 32±4

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kg/m2) underwent a 4-hour 75-g oral glucose tolerance test at baseline and after one year’s randomised and blinded intervention with placebo (n=54) or liraglutide, 1.8 mg once-daily, (n=48). During the trial, 10 women withdrew from the liraglutide group and 9 from the placebo group. Fifteen controls matched for age and BMI were studied once (age: 39±4 years, BMI: 31±5 kg/m2). Dual energy X-ray absorptiometry was used to assess whole-body BMD and whole-body BMC. At baseline, there were no differences between con-trols and women with pGDM with respect to whole-body BMD, whole-body BMC and the total area under the curve (tAUC) during the OGTT for CTX-I and P1NP. Compared to placebo, liraglutide-treatment induced a significantly greater weight loss after 52 weeks (4.9±6 vs. 1.3±5 kg, P<0.005). No changes in whole-body BMD, whole-body BMC, tAUC for CTX-I or tAUC for P1NP were observed in the two groups. We conclude that liraglutide-treatment-induced weight loss in women with pGDM seems not to affect bone turn-over, whole-body BMD and whole-body BMC respectively, suggesting that liraglutide treatment from a bone turnover perspective is safe to use in this population.


2473‑PUBFamilies Defeating Diabetes (FDD): Focus Group Analysis of a Post‑partum Healthy Living Intervention for Women with Gestational Diabetes (GDM)TANIYA NAGPAL, MICHELLE MOTTOLA, RUTH M. MCMANUS, London, ON, Canada

FDD was a postpartum Canadian diabetes healthy living intervention for women with recent GDM within their family context. We report results from a Focus Group program analysis.

Women (W) with recent GDM and interested partners (P) participated in FDD, provided from months 3 to 12. Study components included: DM pre-vention seminar; password-protected website; automatic email hints 2X/month; weekly walking group. W and P finishing 12 month follow-up were invited to a Focus Group to assess perceived value of the program compo-nents. Responses were recorded anonymously; thematic analysis was done identifying most prominent comments; results are reported qualitatively.

Seven people attended (4W, 3P) a 3 hour session. Comments: Walk-ing group: opportunity to socialize with other W (4/4W); should last past 12 months (4/4W); allowed partner to get out of house (3/3 P). Nutrition: assisted healthy choices (4/4W); P felt most engaged in diet component, aided them to make healthier choices (2/3P). P perceived their biggest study role was making healthy food choices (3/3P); 2/3P had not realized their diet was unhealthy until FDD; 2/4W reported being pleased P was learning about diet as this supported their choices. Message vectors: seminar was informa-tive for diet/breastfeeding information (4/4W); 3 months postpartum was appropriate timing (4/4W); email hints 2X/month best for messaging (4/4W). W and P preferred receiving short email hints, none found website useful. All P said seminar helpful but preferred email provision vs. face-to-face. P had no interest in any social media options. All W preferred receiving study hints at least twice a week.

Focus Group analysis of the FDD healthy living program for women with recent GDM and interested partners concluded access to a study website was not of value; whereas helpful study components included: postpartum seminar at 3 months; weekly walking group; frequent automatic provision of healthy living hints by email.

Supported By: International Diabetes Federation

2474‑PUBPoor Adherence to and Reliability of Self‑Monitored Blood Glucose in Women with Gestational Diabetes Mellitus Are Usual and Asso‑ciated with Poor OutcomesEMMANUEL COSSON, BAZ BAZ, FRANÇOISE GARY, DORIAN SANDRE-BANON, ISABELA BANU, SABRINA CHIHEB, YAHYA JABER, PAUL VALENSI, Bondy, France

We aimed to evaluate adherence to self-monitored blood glucose (SMBG) and reliability of blood glucose diary records in women with gestational dia-betes mellitus (GDM), their determinants and prognosis. We prospectively selected women with newly-diagnosed GDM who were referred to our dia-betes management program, spoke national language and had understood glycaemic SMBG techniques and goals. During the first follow-up visit, we collected SMBG results from glucometers and diary records. We analyzed pregnancy outcomes. Data were analyzed over 13±3 days in 91 women. Only 61.5% of them had performed >80% of required measurements. Poor adher-ence was associated with family history of diabetes, social deprivation and non-European origin. Average delay between pre- and post-prandial mea-surements was 131±26 minutes; with 46.5% of women performing 80% of

post-prandial measurements 100-140 minutes after meals. An inadequate delay was associated with origin and a higher HbA1c at inclusion (5.3±0.5 vs. 5.1±0.4%, p=0.03). A poor concordance (23.1% of women had <90% matched values in diary and meter memory) was associated with family history of diabetes; 9.9% of women were considered as dissemblers as they underesti-mated glucose values or did not report a high glucose value more than three times a week. Poor adherence was associated with more preeclampsia (12.2 vs. 1.9%, p=0.049) and inadequate post-prandial delay with a high HbA1c at delivery (5.3±0.4 vs. 5.0±0.3%, p<0.01), despite a higher rate of insulin therapy. To conclude, although women with GDM are considered as highly motivated, poor SMBG adherence and reliability raise concern and are asso-ciated with poor prognosis.

Supported By: Roche Diagnostic France

2475‑PUBDoes Early Gestational Diabetes Mellitus Correspond to Unknown Prediabetes Before Pregnancy? Arguments from Metabolic Mark‑ers at Initial CareEMMANUEL COSSON, LUCIO BIANCHI, FRANÇOISE GARY, DORIAN SANDRE-BANON, YAHYA JABER, ISABELA BANU, CAMILLE PILLEGAND, SABRINA CHI-HEB, MINH TUAN NGUYEN, PAUL VALENSI, Bondy, France

Screening for dysglycemia at first antenatal visit was proposed to detect unknown diabetes apart from pregnancy (Diabetes in pregnancy: DIP). Early gestational diabetes mellitus (eGDM), beginning before pregnancy-induced insulin resistance, might correspond to unknown prediabetes. From a series of 188 pregnant women without known diabetes before pregnancy, we con-sidered 126 women having had skin forearm skin autofluorescence measure (AGE Reader (tm)): 8 women without eGDM and regular GDM (IADPSCG criteria); 62 women with eGDM (<22 weeks of gestation); 48 women with regular GDM but normal early screening; and 8 women with DIP. Women with dysglycemia also had fasting plasma glucose, insulin, fructosamine and HbA1c measurements when they were referred for care. Skin autofluo-rescence (advanced glycation endproducts (AGE), arbitary units) differed according to glycemic status (p<0.05 after adjustment for age): no GDM (1.79±0.32), regular GDM (1.99±0.47), eGDM (2.11±0.48) and DIP (2.42±0.34); with different proportions of women having AGE >1 standard deviation (SD) (41.7; 45.8; 54.8 and 100%, respectively; p<0.05) or >2 SD for age (8.3; 10.4; 25.8 and 50%, respectively; p<0.05). Considering only women with regular GDM, eGDM and DIP, fructosamine (196±12; 203±18 and 223±35 μmol/L, respectively, p<0.0001), and HbA1c levels (4.9±0.5; 5.0±0.4 and 5.8±0.8%; p<0.001) differed significantly but not HOMA-IR index (2.73±1.59; 2.78±1.76 and 4.39±2.41; p=0.057). To conclude, fructosamine and HbA1c are high in case of DIP but not of eGDM. Skin autofluorescence is higher in women with eGDM and DIP than in those without GDM and regular GDM, suggesting that these conditions actually correspond to dysglycemia before pregnancy.

2476‑PUBAssessment of Insulin Resistance and Secretion Indexes in the Nonpregnant Condition as Predictors for Insulin Use of Gestational Diabetes MellitusKYOKO KOHASHI, YUSAKU MORI, ANNA OSAMURA, MASAKO TOMOYASU, YUKI TANABE, TOMOYASU FUKUI, TSUTOMU HIRANO, Tokyo, Japan

Background: Gestational diabetes mellitus (GDM) patients at high risk for insulin therapy need careful follow-up. We examined whether insulin secre-tion and resistance in the non-pregnant condition are useful predictors of insulin use in GDM.

Methods: GDM patients (all Japanese) admitted to Showa University Hos-pital between December 2004 and February 2016 were recruited retrospec-tively. Insulin therapy was initiated when a self-monitored blood glucose level over 100 mg/dL in the fasting state or 120 mg/dL 2 hours after a meal was consecutively observed. Insulin secretion indexes (ISIs: insulinogenic index [II], homeostasis model assessment [HOMA]-β, and area under the curve of insulin/glucose [AUC I/G]), insulin resistance indexes (IRIs: HOMA-R and composite index [CI]), and disposition index (DI) were calculated from a 75-g oral glucose tolerance test conducted 6 to 8 weeks after delivery. The odds ratio per unit change is shown with a 95% confidence interval.

Results: Insulin-treated GDM (111 patients out of 393) showed higher HOMA-R and lower CI in contrast to similar ISIs. In univariable logistic regression, IRIs, but not ISIs, were associated with insulin use. In multiple logistic regression with the simultaneous method, DI or a combination of one IRI and one ISI was used in addition to diabetes family history, age, gestational week at diagnosis, body mass index prior to pregnancy, and body weight change during the gestational period. Although the model using HOMA-R and -β showed the highest coefficient of determination (R^2), the

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value was only 0.092 (p<0.001; HOMA-R: 1.95 [1.20-3.16], p<0.01; HOMA-β: 0.99 [0.98-1.00], p=0.02).

Conclusion: Although insulin resistance and secretion assessed as HOMA-R and -β in the non-pregnant condition are predictors for insulin use in GDM, their clinical usefulness is limited.

2477‑PUBGestational and Pregestational Diabetes Exposure In Utero: Valida‑tion of a Definition for Use in Administrative DataELIZABETH A.C. SELLERS, RANDALL FRANSOO, DAN CHATEAU, HEATHER PRIOR, ANGELA TAN, HUI CHEN, BRANDY A. WICKLOW, Winnipeg, MB, Canada

Background: There are reported differences in the impact of gestational (GDM) vs. pregestational diabetes (PGDM) exposure on the metabolic health of offspring making differentiation imperative.

Aim: To determine the best administrative data case definitions for GDM and PGDM in pregnancy.

Methods: We compared the performance of several case definitions for GDM and PGDM within the administrative health data housed in the Mani-toba Population Health Research Repository at the Manitoba Centre for Health Policy to an identified population of women in whom the diagnosis of GDM or PGDM was known from the clinical database of the Diabetes Education Resource for Children and Adolescents (DER-CA). The DER-CA database contains maternal diabetes status during pregnancy collected through careful history and corroborating information and includes women diagnosed with type 2 diabetes in childhood whose pregnancies were thus all complicated by PGDM. Linkage of mother-child dyads is possible within the Repository. ICD 9/10 diagnosis codes and physician tariff codes were used to identify diabetes in the biologic mother of children with type 2 dia-betes identified from the DER-CA database. The timing of the diagnosis of diabetes in the mother with respect to the gestational age of the pregnancy was determined.

Results: The best administrative definition of GDM exposure was any inci-dent code for diabetes (diabetes or GDM) > 25 weeks gestation and < 12 weeks post-partum (sensitivity 81%, PPV 64%). PGDM exposure was best defined in administrative data as an incident code for diabetes (excluding GDM) in the mother prior to the pregnancy of the index child or within the first 24 weeks (inclusive) of pregnancy (sensitivity 91%, PPV 92%).

Conclusion: We validated administrative definitions for GDM and PGDM exposure. The PGDM definition has superior performance. These definitions can be used to differentiate GDM and PGDM exposure in studies utilizing administrative data.

Supported By: Children’s Hospital Research Institute of Manitoba

2478‑PUBGlycated Haemoglobin in Gestational Diabetes Predicts Need for Medical/Obstetric Intervention and Higher Postnatal Glucose LevelsMALIHA IQBAL, LING LING CHUAH, STONNY E. JOSEPH, Margate, United Kingdom, Ashford, United Kingdom

The value of glycated haemoglobin (A1c) in gestational diabetes (GDM) is controversial. Its routine use is not recommended despite its link to fetal weight (FW) in established diabetes. The role of A1c in predicting the need for medical/obstetric intervention (I) and future maternal metabolic state is not known. We set out to explore the relationship between maternal A1c, I and 3 months post-natal glycaemic status (PNG).

Retrospective analysis of 25 GDM pregnancies was performed. Data on maternal weight, A1c, metformin and/or insulin use, FW and PNG were obtained. Patients were divided into 2 groups; 10 higher (HA) and 15 lower (LA) A1c using 35mmol/mmol (5.3%) as cut off. The pregnancy outcomes were compared and unpaired test performed with p value< 0.05 deemed significant. Data is expressed as mean±SD.

A1c was performed at a mean gestational age of 29.4±2.9 (HA) and 27.7±3.7 weeks (LA). BMI and blood pressure was higher in the HA group compared to LA (30.4±5.3 vs. 28.8±5.2kg/m2; 125.6±20.6/69.4±10.8 vs. 112±8.3/65.1±9.3mmHg, p=0.035) as was fasting glucose (5.9±0.8 vs. 4.5±0.4mmol/L, p<0.002). 50% of the HA required Metformin/insulin and 40% required obstetric intervention (only 25% of LA required any form of I). PNG was also significantly higher in the HA group (e.g., 2 hour post glucose load levels of 8.0±2.1 vs. 5.1±0.9mmol/L, p<0.002). There was a non-signifi-cant trend toward higher FW in HA.

Our data suggest that GDM patients with A1c above 35mmol/mol have a worse metabolic/haemodynamic profile and are more likely to require inter-vention. They also had higher PNG and a tendency to macrocosmic babies. We conclude that A1c remains a valuable biochemical parameter in GDM

and important in predicting the risk of future prediabetes. The small numbers however suggest the need for larger scale studies to confirm our findings.

2479‑PUBThe Prevalence of Gestational Diabetes in the Province of Trento, Trend 2010‑2015 and Adverse Neonatal OutcomesSILVANO PIFFER, RICCARDO PERTILE, TIZIANA ROMANELLI, Trento, Italy

Introduction: A blood glucose control at the initial assessment (before the 13th week of gestation) and at a second check between the 24-27 week is recommended in Italy for the monitoring of physiological pregnancy. These data as all data concerning the characteristics of the mother, the care during pregnancy and childbirth are registered in the medical birth register of the province of Trento.

Aims: To estimate the prevalence of gestational diabetes mellitus (GDM) in pregnant women assisted at the birth centers of Trento Province from 2010 to 2015, verifying the differences in relation to citizenship and the impact on the newborns.

Methods: A retrospective birth cohorts study was conducted for the years 2010-2015, including a total of 29.025 pregnant women. The annual GDM prevalence was calculated analyzing the data according to nationality and whether the foreign, the geographical area of origin. The diagnostic criteria for the definition of GDM are those of IADPSG. Maternal Characteristics and pregnancy outcomes were analyzed.

Results: The average GDM prevalence was 4.2%, increasing since 2010 (2.6%) to 2015 (4.6). The prevalence is higher in foreign (6.3%) than the Ital-ian (3.5%) with a statistically significant difference (p <0.0001). Among the foreigners, the prevalence is greater, with a statistically significant differ-ence (p <0.0001) in African (9.5%) and Asian (10.5%) nationalities.

In GDM mothers there is an excess of stillbirths, born with birth defects and an excess of preterm, low birth weight and hospitalized at birth (statisti-cally significant) infants.

Conclusions: GDM is increasing in Trento province. Excess in foreign, par-ticularly in some specific ethnic groups are confirmed, as well as an excess of adverse events for newborns. Given the recent migration flows it has recom-mended an effective state control model.

2480‑PUBIdentifying Women with Recent Gestational Diabetes at Greatest Need of Early Postpartum Testing for DiabetesMICHELE DREHMER, CRISTINA CASTILHOS, ADRIANA COSTA E FORTI, RUBEN LADWIG, BRUCE B. DUNCAN, MARIA INÊS SCHMIDT, Porto Alegre, Brazil, Fortaleza, Brazil

Background: Gestational diabetes (GDM) is a strong risk factor for future diabetes, which justifies postpartum screening. Yet, gives the overwhelming duties of recent motherhood, adherence to testing is low, particularly early on. The purpose of this study is to assess diabetes risk and related factors over the first 20 months postpartum among women with GDM participating in the LINDA-Brasil Study.

Methods: LINDA-Brasil, an ongoing clinical trial of diabetes prevention postpartum, is nested within a cohort of women with recent GDM. The cohort currently comprises 2856 women with GDM recruited from high risk pregnancy clinics. We used various approaches to stimulate OGTTs after 8 weeks postpartum, including nearby, no cost testing, phone reminders and free clinic visits. Cox regression was used to estimate relative risks (RR) of developing diabetes.

Results: Mean (SD) BMI before pregnancy was 30.1 (6.4) kg/m2 and mean age 31.9 (6.2) y; 19.3% used insulin during pregnancy and an additional 16.3% oral hypoglycemic agents. By six months postpartum, 44% had under-gone diabetes screening; among those who completed an OGTT, diabetes incidence was 2% for non-insulin users and 16% for insulin users. By 20 months postpartum, 110 (8%) of those tested had developed diabetes, with corresponding incidences being 4% and 27%, respectively. Use of insulin and of hypoglycemic medication during pregnancy were associated with RR of developing diabetes of 6.0 (95% CI 3.9-9.1) and of 1.9 (95% CI 1.3-2.9), respectively. Each 5 unit increase in BMI increased risk by 20% (RR 1.2; 95% CI 1.0-1.4). Most incident cases used insulin (65%) or oral hypoglycemic agents alone (17%) during pregnancy.

Conclusion: Use of insulin or oral hyperglycemic agents during pregnancy identifies most future cases of diabetes developed over 20 months postpar-tum, constituting a simple means of targeting those at highest need of early postpartum testing.

Supported By: Brazilian National Counsel of Technological and Scientific Devel-opment (563942/2010-0); Eli Lilly and Company

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2481‑PUBAssociation between Peroxisome Proliferator‑Activated Receptor Pro12Ala Polymorphism and Gestational Diabetes MellitusDI MAO, PING LI, SHUO LIN, LING LI, JIANHUI FAN, Guangzhou, China

The polymorphisms of peroxisome proliferator-activator receptor-gamma2 (PPAR-γ2) have been suggested to affect glucose metabolism. This study aims to explore the possible association between PPAR-γ2 gene Pro-12Ala polymorphism and gestational diabetes mellitus (GDM). Two hundred pregnant women diagnosed as GDM and 200 non-GDM pregnant women in our hospital were recruited from June 2015 to December 2015. There were no statistically significant differences in baseline characteristics between the two groups. The Pro12Ala polymorphism (genotype Pro/Pro, Pro/Ala) were found in both GDM and control groups. A significant difference was observed in frequencies of Ala allele between GDM group (4%) and control group (8.8%) (P<0.05, odds ratio 0.49 (95% CI 0.26-0.92)). There were no statistical differences between genotype and prenatal BMI, fasting glucose, HDL, triglyceride, LDL (P>0.05). Our study suggested that PPAR-γ2 Pro12Ala polymorphism were associated with GDM. Ala allele in PPAR-γ2 may be an protect factor of GDM.

2482‑PUBAssessing the Outcome of Universal vs. Risk‑Based Screening for GDM in Resource Limited Setting of the Niger‑DeltaROSEMARY N. OGU, OSITA C. JOHN, OMOSIVIE MADUKA, SUNDAY CHINENYE, Port Harcourt, Nigeria

Diabetes is a growing NCD epidemic. In Pregnancy, early detection is essential to improve fetomaternal outcomes and mitigate future type 2 dia-betes and co-morbidities.

Objective: To assess the outcome of universal or risk-based Screening for GDM in a resource-limited setting.

Methods: A retrospective cohort survey of antenatal clinic attendees who accessed care between January to October 2014 when screening for GDM was universal and November 2014 to October 2015 when screening for GDM was selective risk-based. Data relating to diagnoses of GDM using the new WHO criteria, maternal characteristics such as age, parity, maternal and fetal outcomes such as gestational age at delivery, mode of delivery, birth weight, Apgar scores, etc were retrieved. Data analysis was done using SPSS version 21.

Results: Prevalence of GDM was 15.2% when universal screening was done and 3.2% when selective risk-based screening was done. Multiple logistic regression analysis showed that for every unit increase in parity, women had a 63% greater odds of being screened for GDM at the antenatal clinic. (Odds ratio = 0.63; p value=0.00; C.I = 0.50 to 0.79). With selective risk-based screening, there was no significant difference between Apgar scores and the prevalence of stillbirths in babies born to women diagnosed with GDM compared with babies born to women not screened for GDM.

Conclusion: Selective risk-based screening for GDM missed cases of GDM. The need for universal screening for GDM in resource-limited settings is reiterated.

EPIDEMIOLOGY—AGING

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2484‑PUBA Comparison of Characteristics of Elderly and Younger Adults with Type 2 Diabetes Mellitus (T2DM) after Failure of Oral Antidiabetic Drugs (OAD)JI HAI CHEN, XIAO JUN OUYANG, TIAN TIAN LU, KE WANG, YUN CHEN, LI SHEN, RONG WEN BIAN, Nanjing, China, Shanghai, China

The aim of this study was to compare the glycemic profiles of elderly vs. younger Chinese patients with T2DM at the time of insulin initiation to provide rationale for tailored insulin therapy. Data were extracted from a diabetes patient registry database of Jiangsu Province Geriatric Hospital, Nanjing, China. Medical records of patients with T2DM (aged ≥18 years [yrs] and HbA1c ≤7%) who had initiated insulin therapy from Jan 2005 to Sep 2014 were analyzed. Data were stratified into 2 groups: elderly patients (≥65 yrs of age) and younger patients (<65 yrs of age). Patient demographics, disease duration, glycemic profiles, and OAD usage prior to insulin initiation were compared between groups. A univariate analysis followed by multiple logistic regression was applied to confirm the findings. Data from 165 Chi-nese patients with T2DM (elderly: 104; younger: 61) were analyzed. Demo-graphic characteristics were similar in both groups, the majority of patients were male (61.5% vs. 75.4%, P=0.07). Duration of T2DM was higher among elderly patients than younger patients (14 vs. 10 yrs; P=0.0002). Usage of OADs was similar in both groups (P=0.93), with a majority of patients using 2 OADs (57% vs. 60%, P=0.93). Both groups had a similar HbA1c level (8.54 vs. 8.77%; P=0.39). However, elderly patients had significantly lower fasting (8.09 vs. 8.97mmol/L; P=0.045) and numerically higher postprandial glucose levels (15.1 vs. 13.7 mmol/L; P=0.12) prior to insulin initiation than younger patients. The mean blood glucose [BG] excursion level (mmol/L) was sig-nificantly higher among elderly patients as compared with younger patients (6.97 vs. 4.62; P=0.009), which was confirmed by the multiple logistic regres-sion (OR [95% CI]: 1.17 [1.02, 1.35]; P=0.03). The present analysis showed that Chinese elderly patients with T2DM after OAD failure had significantly greater BG excursions than younger patients. Tailored therapy may need to be chosen accordingly.

2485‑PUBReal‑Life Efficacy and Safety of Adding SGLT2 Inhibitors to Elderly DM2 Already Treated with DPP‑IV Inhibitors or GLP‑1R AgonistsCARLOS TRESCOLI, PATRICIA PLATERO, JOSE ALEJANDRO ARAZO, EDUARDO ROVIRA, ANA TRESCOLI, ANDREA PEREZ, Alzira, Spain

Management of DM2 in Elderly is challenging because little research, morbidities, frailty, polypharmacy and risk of hypoglycemia Combination of new antidiabetic drugs (ADD) claim to be more effective and safe.

We evaluated the real world safety and efficacy of adding an SLGT2 Inhib-itor to an Elderly not controlled DM2 already treated with a DPP-4 Inh or a GLP-1 RA at least for one year and if their outcomes are different.

We studied 102 Elderly DM2, treated with DPP-4 Inh (n= 54) and GLP-1 RA (n= 48) besides other ADD. SLGT-2 Inh. was added during a mean period of 19, 5 months in a Spanish Health Department. Data was collected from com-puterized Primary and Hospital Records before and after starting SLGT-2 Inh.

Baseline Data: (DPP-4 Inh. and GLP-1 RA) Mean age 70,2 vs. 69,2 years, Mean period DM2: 12 vs. 13,4 years. Comorbidities: Hypertension 82 vs. 85%, Hypercholesterolemia 88 vs. 85%, BMI > 30 56 vs. 62% and had a previous cardiovascular or heart failure event: 50 vs. 53%. Baseline ADD: Metformin 76,5 vs. 82,3%, Insulin 32,3 vs. 38,2%, Sulphonylurea 38,2 vs. 26,5%, Repaglinide 20 vs. 9% and Pioglitazone, 9 vs. 15%

Results pre- and post-SLGT-2 Inh: (DPP-4 Inh and GLP-1 RA) HbA1c: 8,8 vs. 7,6%, (S) and 8,4 vs. 7,3%, (S); Weight: 87,4 vs. 83,0 kg, (S) and 92,9 vs. 88,7 kg, (S); Systolic Blood Pressure (SBP): 134,4 vs. 133,1 mmHg, (NCS) and 136´7 vs. 131,2 mmHg, (S); There were no significant differences in Heart Rate, DBP, Lipid Profile, and Urinary function before and after SLGT-2 Inh

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clinical therapeutics/new technology— glucose...

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