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Screening for Unidentified Diabetes

Heather P. Whitley, PharmD, BCPS, CDEAssociate Clinical Professor of Pharmacy PracticeAuburn University Harrison School of Pharmacy

Clinical Pharmacy Specialist and Co-Director of ResearchBaptist Health; Montgomery Family Medicine Residency Programwhitlhp@auburn.edu

Please text

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Funded: Diabetes Hands Foundation via The Big Blue Test Alabama Department of Public Health

Colleagues: Larry Skelton, MD and the Moundville Medical Clinic Montgomery Family Medicine Residency Program

Former students: Drs Seth Edwards and Katherine Fuller

Statistical Support: Courtney Hanson and Jason M. Parton, PhD University of Alabama, Department of Information Systems

Disclosures & Acknowledgements

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ObjectivesAccording to the American Diabetes Association:

List diagnostic glycemic thresholds for diabetes and prediabetes

Compare and contrast A1C to blood glucose in terms of diagnostic benefits

Discuss benefits of point-of-care versus venipuncture laboratory measures for diabetes

List screening criteria for diabetes

Basic Pathophysiology

Hyperglycemia

Impaired insulin secretion Insulin resistance

Ominous Octet

DeFronza RA. Diabetes. 2009;58:773-95. Tahrani AA, et al. Lancet. 2011;378:182-97.

GLP1, DPP4i, AGi

GLP1, DPP4iAmylin mimetic

SU, GLP1 DPP4i

SGLT2i

GLP1

TZD, METMET GLP1 DPP4i

TZD

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Permanent organ damage

Macrovascular risks Heart attack, strokes

Microvascular risks Blindness

Kidney failure

Amputation

Consequences

http://www.cdc.gov/diabetes/home/index.html

Age-Adjusted Percent, Adults 2014

Puerto Rico 14.2West Virginia 12 Mississippi 11.9 Alabama 11.8 Tennessee 11.7 Guam 11.6 Arkansas11.5 Kentucky 11.3

National 9.1

http://www.cdc.gov/diabetes/home/index.html

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CDC Identified “Diabetes Belt”

Diabetes Diagnosis Rate: 11.7% Inside Diabetes Belt

8.5% Outside of Diabetes Belt

http://www.cdc.gov/diabetes/pdfs/data/diabetesbelt.pdf

EpidemiologyNational Statistics (2014)

Diabetes Prevalence: 9.1% (29.1 million) 72% (21 million) aware/diagnosed

27.8% (8.1 million) unaware/undiagnosed

Incidence: 1.7 million/yr

Prediabetes Prevalence: 37% (86 million) 11% aware; 89% unaware

Alabama Statistics (2014)

Diabetes Prevalence: 11.8% per CDC

Prediabetes Prevalence: 37% (1.2 million) 7.2% aware; 92.8% unaware

www.americashealthrankings.org/ALhttp://www.cdc.gov/brfss/brfssprevalence/

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Diabetes Prevention Program

N=3234 people with prediabetes (average A1C 5.9%)

Treatment arms: Placebo

Metformin 850 mg BID

Lifestyle-modification program: Goal 7% weight loss, 150 min weekly physical activity

Average follow-up = 2.8 years

Baseline demographics: 51 yo, BMI 34; 68% women; 45% minority

N Engl J Med. 2002;346(6):393-403.

Diabetes Prevention Program

Year

Cum

ulat

ive

Inci

denc

e of

Dia

bete

s

N Engl J Med. 2002;346(6):393-403.

58% reduced incidenceNNT = 6.9

31% reduced incidenceNNT = 13.9

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Blood glucose (BG) (mg/dL)

Hemoglobin A1C (A1C) (%)

Diagnostic Methods and Criteria

Test Diabetes Prediabetes

OGTT ≥ 200 mg/dL 140-199 mg/dL

Fasting BG (FBG) ≥ 126 mg/dL 100-125 mg/dL

Random BG ≥ 200 mg/dL+ symptoms

---

Test Diabetes Prediabetes

A1C ≥ 6.5 % 5.7 – 6.4 %

Symptoms of Hyperglycemia

Blood glucose (BG) (mg/dL)

Hemoglobin A1C (A1C) (%)

Diagnostic Methods and Criteria

Test Diabetes Prediabetes

OGTT ≥ 200 mg/dL 140-199 mg/dL

Fasting BG (FBG) ≥ 126 mg/dL 100-125 mg/dL

Random BG ≥ 200 mg/dL+ symptoms

---

Test Diabetes Prediabetes

A1C ≥ 6.5 % 5.7 – 6.4 %

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A1c to Average Glucose

Glycemic assessment of the past 2-3 months

Prospective controlled study

Location: Hale County family medicine medical clinic

Objective: To improve the undiagnosed rate of diabetes by screening with POC A1C tests and compare that rate to standard of care

Duration: 1 year April 2013 – March 2014

Rural Study Design

Traditional Counties of the Alabama Black Belt

Source: Center for Business and Economic Research, The University of Alabama

16% Diabetes Prevalence

Study Criteria

Inclusion

Patient at the Moundville Medical Clinic

45 years-of-age or older

Exclusion

PMH of type 1 or type 2 diabetes

Pregnancy

Oral or injectable steroid use within 3 months

A1C test in past 12 months

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Electronic medical record (EMR) review Standard Practice Arm Wednesday medical appointments EMR evaluations to determine frequency of appropriate

screening per ADA guidelines

Active Screening arm Tuesday medical appointments EMR evaluation + live confirmation of meeting study criteria Lack of PMH of diabetes Non pregnant No steroid use (IV or PO) within past 3 months

Offered free POC hemoglobin A1C test

Methods: Pre-Screening Process

Bayer A1C Now+ point-of-care device

Secondary questions Comorbidities Hyperglycemic symptoms

All A1C results documented in EMR ≥ 6.5% practitioner notified 5.7-6.4% prediabetes brochure; EMR flag > 5.7% consultation by a Certified Diabetes Educator free-of-charge

Live Evaluation

Screening and Enrollment

Consort Diagram

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Baseline Demographics

Active Screening Arm (N=164) Control Arm (N=324)

Characteristic N (%) Mean Std. Dev. N (%) Mean Std. Dev.Age (years) 63.5 10.28 63.3 11.71

BMI (kg/m2) 31.0 7.08 29.3 7.08 Morbidly Obese (BMI>40) 16 (10) 46.3 5.13 30 (9) 44.2 4.19

Obese (BMI 30‐40) 60 (37) 34.2 2.69 90 (28) 34.2 2.65 Overweight (BMI 25‐29) 58 (35) 27.5 1.46 106 (33) 27.2 1.38

Healthy Weight (BMI 18.5‐25) 28 (17) 22.5 2.16 95 (29) 21.9 2.21 Did Not Report 2 (1) 3 (1)

Race/Ethnicity African American 12 (7) 27 (8) Caucasian 142 (87) 285 (88) Did Not Report 10 (6) 12 (4)

Sex Female 91 (55) 209 (65) Male 73 (45) 113 (35)

Possesses Health Insurance 155 (95) 302 (93)

Actively Screened Arm (n=164)

Control Arm (n=324)

A1C Outcomes

A1C Result (%) N (%) Mean Std. Dev.

Total 164 (100) 5.80 0.51

Diabetes (≥ 6.5%) 16 (10) 6.86 0.19

Prediabetes (5.7-6.4%) 88 (53) 5.93 0.47

Euglycemia (A1C ≤ 5.6% ) 62 (37) 5.34 0.23

A1C Result (%) N (%)

Eligible but not screened 252 (78)

Eligible and screened 73 (22)

Diabetes 6 (8)

Prediabetes 24 (33)

Euglycemia 43 (49)

Diabetes: N=30Prediabetes: N=174

Comparative Analysis of Screening Methods

Active Screening Arm n (%)

Standard Practice Arm n (%)

Screening Method

A1C 164 (100) 4 (5)

Blood Glucose 0 (0) 70 (96)

Screening Outcome

Diabetes 16 (10) 6 (8)

Pre-Diabetes 88 (53) 24 (33)

Euglycemic 62 (37) 43 (59)

χ2 9.86, df 2, p 0.0072

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A1C Outcomes by DemographicsVariable Column1 N (%) Mean A1C Std. Dev

EthnicityAA 12 7% 6.03 0.53

Caucasian 142 87% 5.77 0.51Sex Male 73 45% 5.73 0.42

Female 91 55% 5.85 0.56Advised to Change Diet Yes 66 40% 5.80 0.40

No 98 60% 5.80 0.64Advised to Exercise More Yes 78 48% 5.79 0.60

No 86 52% 5.81 0.41Advised to Lose Weight Yes 61 37% 5.80 0.64

No 103 63% 5.80 0.41History of High Cholesterol Yes 100 61% 5.79 0.52

No 64 39% 5.82 0.49History of High Blood Pressure Yes 95 58% 5.82 0.56

No 69 42% 5.78 0.43History of Gestational Diabetes Yes 3 2% 6.03 0.51

No 161 98% 5.80 0.51

History of "Pre-Diabetes"Yes 11 7% 5.81 0.71No 153 93% 5.80 0.49

A1C Outcomes by Symptoms

Variable Column1 N (%) Mean A1C Std. Dev

Blurred Vision Yes 25 15% 5.87 0.63

No 139 85% 5.79 0.48

Difficulty Concentrating Yes 31 19% 5.85 0.75

No 133 81% 5.79 0.43

Dry Mouth Yes 49 30% 5.92 0.57

No 115 70% 5.75 0.47

Feeling Tired or Weak Yes 72 44% 5.83 0.60

No 92 56% 5.77 0.43

Frequent Urination Yes 38 23% 5.82 0.53

No 126 77% 5.80 0.50

Headaches Yes 36 22% 5.76 0.70

No 128 78% 5.81 0.44

Leg Cramps Yes 65 40% 5.82 0.55

No 99 60% 5.78 0.48

Thirst Yes 30 18% 5.92 0.68

No 134 82% 5.77 0.46

Weight LossYes 24 15% 5.59 0.44

No 140 85% 5.84 0.51

A1C Outcomes by Symptoms

Analysis of Covariance and Adjusted Means

Variable Estimate Standard Error

t Value P Value

Race/Ethnicity 0.150 0.157 0.95 0.34

Sex 0.081 0.080 1.00 0.32

Age (years) 0.014 0.004 3.48 0.0007

BMI (kg/m2) 0.016 0.006 2.64 0.0094

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63% of the actively screened unknowingly living in chronic hyperglycemia Risk for hyperglycemia increase with BMI and age

No specific comorbidity or symptom or constellation of symptoms better projects the coincidence than others

Control arm was severely under screened Blood glucose did not as effectively identify chronic

hyperglycemia

Proactive screening asymptomatic adults is critical to help facilitate early diagnosis of diabetes

A1C appears to more effectively identify chronic hyperglycemia than blood glucose

Conclusion & Impact

Blood Glucose versus A1C

A1C = Glycemic assessment of the past 2-3 months

Factors Contributing to Variation Biologic Intraindividual; interindividual variation

Preanytical Issues pertaining to the specimen before it is measured

Analytical Differences result from the measurement procedure itself

Sacks DB. Diabetes Care. 2011;34:518-523.Enzo B; Tuomilehto J. Diabertes Care. 2013;34(2):S184-S190.

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Fasting Blood Glucose A1C

Critique of Diagnostic Methods

Advantages Easily automated assay Widely available InexpensiveDisadvantages Reflects glucose

homeostasis at a single point Must fast ≥ 8 hours Large biologic variation Numerous factors alter

glucose (stress, illness) Diurnal variation Varies with source (venous,

capillary, arterial blood) Source: plasma, whole blood Sample not stable FBG less tightly linked to

complications vs A1C

Advantages Reflects long-term glucose Subject need not fast Samples may be obtained

anytime of day Very little biologic variation Not altered by acute factors

(stress, exercise) Sample stable Assay standardized across

instruments Outcome predicts risk of

microvascular complication Disadvantages Altered by other factors

(erythrocyte life span, ethnicity) Interferences

(hemoglobinopathies) Not available in some labs Cost

Sacks DB. Diabetes Care. 2011;34:518-523.

DCCT Results

A1C Predicts Associated Risk of Microvascular Complications

NEJM. 1993;329(14):977-986.

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A1C Predicts Risk of Developing Diabetes

A1C Risk of Developing diabetes in 5 years

5 – 5.5% 3 – 12%

5.5 – 6% 9 – 25%

6 – 6.5% 25 – 50%

Pradhan, et al. Am J Med. 2007;120(8):720-727. Selvin, et al. N Engl J Med. 2010;362:800-811. Zhang, et al. Diabetes Care. 2010;33(7):1665-1673.

A1C Predicts Diabetes Risk

Zhang, et al. Diabetes Care. 2010;33(7):1665-1673.

A1C

Annual Incidence of Diabetes A1C

Inci

dent

Rat

e of

Dia

gno

sed

(per

100

0 pe

rson

-yr)

Selvin, et al. N Engl J Med. 2010;362:800-811.

Prospective controlled study

Location: Montgomery County family medicine residency clinic

Objective: To improve the undiagnosed rate of diabetes by screening with POC A1C tests and compare that rate to previous practices

Duration: 1 year August 2015 – present

Urban Study Design

Traditional Counties of the Alabama Black Belt

Source: Center for Business and Economic Research, The University of Alabama

13.5% Diabetes Prevalence

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Study Criteria

Inclusion

Any patient at the MFMRP

Exclusion

PMH of type 1 or type 2 diabetes

Recommended: Pregnancy

Oral or injectable steroid use within 3 months

A1C test in past 12 months

Active Screening Arm (August 2015 - present) Physicians (medical residents or attending)

Identified patients to screen for diabetes ANY patient seen in clinic without a PMH of diabetes

Offered POC hemoglobin A1C test

Physician documented reasons to screen each patient

Analyzed for demographic information, A1C outcomes, criteria for screening

Methods: Screening Process for Active Screening Arm

To fortify and verify medical resident education Study purpose and process

Screening recommendation per ADA

Diagnostics of diabetes and prediabetes

Pre-Study Physician Education

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Add Poll Everywhere question

Besides age, what are other criteria to screen an individual for diabetes?

Reasons for Screening in Asymptomatic Adults

Age of initiation: 45 yearsFrequency: Every 3 years; Annually in prediabetes

Reasons for Screening in Asymptomatic Children

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Previous Practice Arm (October 2014 – April 2015) EMR evaluation

n=200 random patient encounters n=100 (ages 10-44 yo); n=100 (ages > 45 yo)

Meeting criteria: Lack of PMH of diabetes, Non-pregnant, No steroid use (IV or PO) within past 3 months, A1C screening in past year

Encounters analyzed for demographics, meeting ADA screening qualifications, A1C screening performed, outcome, diagnosis, and initial drug therapy

Methods: Screening Process for Control Arm

Results: DemographicsActive Control Groups All Controls

N=22410‐44 years old

(n=100)≥45 years old

(n=100)Control Total

(n=200)

Age (yrs; mean ± SD) 49.3 27.39 ± 9.87  61.67 ± 11.10 44.53 ± 20.13 Female n (%) 154 (69) 63 62 125  (63)

Ethnicity n (%)Black 187 (83.5) 73 56 129 (64.5)White 28 (12.5) 20 36 56 (28)

Hispanic 6 (2.7) 7 8 15 (7.5)Asian 1 (0.5) 0 0 0 (0)

Weight (kg; mean ± SD) 98.8 99.00 ± 61.35 85.37 ± 21.42 92.19 ± 46.34BMI (kg/m2; mean ±SD) 34.7 33.18 ± 6.46 30.06 ± 7.17 31.62 ± 6.98

Screening Results

Prospective RetrospectiveA1C

Encouraged (n=224)

10-44 yearsold

(n=100)

≥45 yearsold

(n=100)Control Total

(n=200)Qualified n (%) ‐‐ 85 (85) 100 (100) 185 (92.5)

Screened n (%) 224 (100) 8 (9.4) 6 (6) 14 (7.5)

Diagnosed (n) (% of screened)Diabetes (A1C ≥ 6.5) 39 (17.4) 3 (37.5) 0 (0) 3 (21)

Prediabetes (A1C 5.7‐6.4) 84 (37.5) 3 (37.5) 3 (50) 6 (43)Euglycemic (A1C < 5.7) 101 (45) 2 (25) 3 (50) 5 (36)

Wrong or omitted diagnosis, n (% screened) 3 (37.5) 2 (33.3) 5 (35.7)Therapy for Diabetes (n) 1 0 1 Therapy for Prediabetes (n) 3 2 5

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Results: Active Screening by A1C Outcomes

A1C Category N (%) Age BMI A1C Result

Diabetes (≥ 6.5) 39 (17.4) 56 35 9.1

Prediabetes (5.7 ‐ 6.4) 84 (37.5) 52 36 6

Euglucemic (≤ 5.6) 101 (45) 42 35 5.3

Report Total 224 (100) 49 35 6.4

Black

White

Total

0

10

20

30

40

50

60

70

80

90

100

TotalFemale

Male

Results: Active Screening Race & Sex by A1C Category

Percent with A1C 5.7 – 6.4% (Prediabetes)

58%

63%

100%

11%

37%

30%5%

88%

5%

Total

Female

Male

0

10

20

30

40

50

60

70

80

90

100

WhiteBlack

HispanicTotal

0%

Results: Active Screening Race & Sex by A1C Category

Percent with A1C ≥ 6.5% (Diabetes)

58%

23%

80%70 %

30%

13%7.5%5%

5%5%

100%

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Total

Female

Male

0

2

4

6

8

10

12

WhiteBlack

HispanicTotal

Results: Active Screening Race & Sex by A1C Category

Average A1C Outcome ≥ 6.5% (Diabetes) by Demographic

9%

10.4%

9.3%9.7%

9%8.2%

8.2%

9.7%9%

8.3%

9.2%

Reasons Screening Conducted

Criteria for Screening N (%)

Total 758 (100)

Overweight or obese 173 (22.8)

High-risk race/ethnicity 134 (17.7)

≥ 45 years old 126 (16.6)

Hypertension 84 (11.1)

Physical inactivity 73 (9.6)

Previous A1C ≥ 5.7%, IGT, or IFG 49 (6.5)

HDL < 35 md/gL; triglycerides > 250 mg/dL 15 (2)

Other (acanthosis nigricans) 14 (1.8)

History of CVD 10 (1.3)

First-degree family history 6 (0.8)

GDM or Delivering baby weighing > 9 lbs 4 (0.5)

Women with PCOS 2 (0.3)

Reasons Screening Conducted

Criteria for Screening All

Total n (%) 758 (100)

Overweight or obese 173 (22.8)

High-risk race/ethnicity 134 (17.7)

≥ 45 years old 126 (16.6)

Hypertension 84 (11.1)

Physical inactivity 73 (9.6)

Previous A1C ≥ 5.7%, IGT, or IFG 49 (6.5)

HDL < 35 md/gL; TG > 250 mg/dL 15 (2)

Other (acanthosis nigricans) 14 (1.8)

History of CVD 10 (1.3)

First-degree family history 6 (0.8)

GDM or Delivering baby wt > 9 lbs 4 (0.5)

Women with PCOS 2 (0.3)

Criteria for Screening All A1C ≥ 6.5 5.7-6.4 A1C < 5.7

Total n (%) 758 (100) 170 (100) 287 (100) 309 (100)

Overweight or obese 173 (22.8) 29 (17.1) 66 (23) 79 (26)

High-risk race/ethnicity 134 (17.7) 27 (15.8) 48 (16.7) 62 (20)

≥ 45 years old 126 (16.6) 30 (17.6) 53 (18.5) 46 (15)

Hypertension 84 (11.1) 16 (9.4) 39 (13.6) 29 (9)

Physical inactivity 73 (9.6) 16 (9.4) 22 (7.7) 35 (11)

Previous A1C ≥ 5.7%, IGT, or IFG 49 (6.5) 24 (14.1) 21 (7.3) 4 (1)

HDL < 35 md/gL; TG > 250 mg/dL 15 (2) 10 (5.9) 3 (1) 2 (0.6)

Other (acanthosis nigricans) 14 (1.8) 2 (1.2) 5 (1.7) 7 (2)

History of CVD 10 (1.3) 6 (3.5) 2 (0.7) 2 (0.6)

First-degree family history 6 (0.8) 10 (5.9) 27 (9.4) 38 (12)

GDM or Delivering baby wt > 9 lbs 4 (0.5) 1 (0.3) 3 (1)

Women with PCOS 2 (0.3) 2 (0.6)

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55% of the actively screened unknowingly living in chronic hyperglycemia Risk for hyperglycemia greatest among: Women > men

Black > white

Overweight / obesity, high-risk ethnicity, age > 45 years prompt an A1C screening most often

Control arm was severely under screened by A1C High A1C did not consistently prompt diagnosis or correct

diagnosis, nor did it stimulate medication initiation

Conclusion & Impact

Combined Study Evaluation Proactive screening is under conducted

Active screening by A1C facilitate identification of unknown hyperglycemia

Greater frequency of hyperglycemia among rural/white population

Greater rate of diabetes among urban/black population

Higher A1C outcomes of those with diabetes among urban/black population

Identified Rural Study Urban Study

Hyperglycemia 63% 55%

Prediabetes 53% 37.5%

Diabetes 10% 17.4%

average A1C 6.86% 9.1%

Recommended Clinic Impact Do not rely on presence of symptom to facilitate screening

Screening all adults 45 years or older

Screening high-risk ethnicities (black) starting at a much lower age ADA 45 years old

USPSF 40 years old

Use A1C for screening versus blood glucose If available, consider POC over venipuncture

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NGSP-Certified A1C POC Instruments

A1C Now AfinionBench Top ModelsHand-Held

DCA Vantage

Axis-Shieldwww.axis-shield.com

Siemenswww.siemens.com

Chek Diagnosticswww.ptsdiagnostics.com

2.5 in

2 in

7.4 in

6.7 in 13.4 in

9 in

10.5 in11.5 inWeight: 0.4 lbs Weight: 11 lbs Weight: 9 lbs

A1C Testing Options

POC Outcomes

Finger prick blood sample

Results available in ~5 minutes

52% intervention rate1

A1C reduction: 1.03 ± 0.33%1 to 0.4 ± 1.65%2

Conventional Outcomes

Venipuncture blood sample Skilled personnel required

Results available next day

27% intervention rate1

A1C reduction: 0.33%1

1 Ferenczi, et al. Endocr Pract. 2001;7(2):85-8.2 Cagliero, et al. Diabetes Care. 1999;22(11):1785-1789.

Diabetes – prevent end-organ damage from chronic hyperglycemia

Prediabetes – opportunity to prevent/delay the onset of diabetes

Weight loss target of 7% Exercise 150 min aerobic exercise weekly

Dietary modification

Reduced incidence by 58%, NNT = 6.9

Metformin initiation Reduced incidence by 31%, NNT = 13.9

Benefits to Early Detection

NEJM. 2002;346(6):393.

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https://doihaveprediabetes.org

What is Prediabetes?When blood glucose is higher than normal, but not high

enough to be diagnosed with type 2 diabetes Are at risk for developing type 2 diabetes

Are at increased risk for stroke and heart disease

Can often be reversed through lifestyle changes

Increase physical activity and weight loss

Earlier diagnosis of prediabetes, the greater the opportunity to reverse the course of the disease

http://www.cdc.gov/diabetes/prevention/index.html

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Screening for Unidentified Diabetes

Heather P. Whitley, PharmD, BCPS, CDEAssociate Clinical Professor of Pharmacy PracticeAuburn University Harrison School of Pharmacy

Clinical Pharmacy Specialist and Co-Director of ResearchBaptist Health; Montgomery Family Medicine Residency Programwhitlhp@auburn.edu