1. 1. Kyle Crisco IPPE-III Ambulatory Care Rotation
2. 2. Describe the pathophysiology, risk factors, signs/symptoms, and diagnosis of type II diabetes Recognize common treatment options for type II diabetes Present an ambulatory care patient case Discuss primary literature concerning the effectiveness of U500 insulin Recommend an assessment and plan for the patient case
3. 3. In 2010, 25.8 million people in the U.S. had diabetes Increasing risk with increasing age Relatively equal for men and women Most common in non-Hispanic whites 7th leading cause of death in 2010 Expensive Types Type I diabetes Type II diabetes Gestational diabetes CDC. National Diabetes Fact Sheet, 2011.
4. 4. Family history Overweight or obesity Sedentary lifestyle Pre-diabetes Gestational DM or baby > 9 lbs Hypertension Dyslipidemia Jalili M. Chapter 219. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e.
5. 5. Obesity Insulin resistance Excess free fatty acids Dysregulation of cytokines -cell dysfunction Initial hyperinsulinemia Postprandial hyperglycemia Excessive hepatic glucose production Impaired control of gluconeogenesis Funk JL. Chapter 18. Pathophysiology of Disease, 6e.
6. 6. Classic Polyuria Polyphagia Polydipsia Others Abdominal pain Fatigue Irritability Drowsiness Blurred vision Numbness or tingling
7. 7. A1c 6.5% Fasting plasma glucose 126 mg/dL Two-hour plasma glucose 200 mg/dL during an oral glucose tolerance test Random plasma glucose 200 mg/dL Used in patients with classic signs/symptoms ADA. Executive Summary: Standards of Medical Care in Diabetes 2014.
8. 8. Lifestyle changes Biguanides Glucophage (metformin) Sulfonylureas DiaBeta, Micronase, Glynase (glyburide) Glucotrol (glipizide) Amaryl (glimepiride) Thiazolidinediones (TZDs) Avandia (rosiglitazone) Actos (pioglitazone) DPP-4 inhibitors Januvia (sitagliptin) Onglyza (saxagliptin) Tradjenta (linagliptin)
9. 9. SGLT2 Inhibitors Invokana (canagliflozin) Incretin mimetic Byetta (exenatide) Victoza (liraglutide) Bydureon (exenatide ER) Amylinomimetic Symlin (pramlintide acetate) Insulin Rapid-acting Short-acting Intermediate-acting Long-acting
10. 10. Type Onset Peak Duration Rapid-acting 15-30 min 1-2 hours 3-6 hours Short-acting 0.5-1 hour 2-3 hours 4-8 hours Intermediate- acting 2-4 hours 4-8 hours 8-18 hours Long-acting 2-5 hours peakless 14- 24 hours U-500 30 min 2-4 hours 10-24 hours Triplitt CL et al. Chapter 83. Diabetes Mellitus. Pharmacotherapy: A Pathophysiologic Approach, 8e. Eli Lilly & Co. Humulin R regular U-500 package insert. 2010.
11. 11. Clinical uses Discomfort at the injection site Severe insulin resistance Cost Genetics
12. 12. Subjective
13. 13. JS 50 y/o Caucasian female HPI JS presented to the clinic concerning her type II diabetes. She has a history of an all or nothing philosophy and has been changing her lifestyle in small increments. However, during the holidays she admits to eating everything she wanted. Nighttime snacking is also a big problem for her, but rationalizes the hand-to-mouth motion is calming for her. Currently, she gives about 20 units of insulin at each meal, though she states she does carb count using a carb factor = 3 and sensitivity factor = 8.
14. 14. SH Does not drink or smoke FH Mother breast cancer, HTN, hyperlipidemia Father alcohol abuse Sister psoriasis Allergies ACEI (benazepril) angioedema Vaccines Influenza (2012) Tdap (2013) Pneumococcal (2006)
15. 15. Glucose readings have improved and mostly 200) Pre-lunch: 110 349 (most 130 180, also has several >200) Pre-dinner: 70 304 (most 80 160) HS: 88 204 (most 100 120 and 180 200)
16. 16. Breakfast Recently began juicing Incorporates vegetables and small portions of fruits Snacks Chips, popcorn, dry cereal Switched to wheat bread except at Chick-Fil-A Orders extra crispy chicken
17. 17. PMH Type II diabetes Neuropathy Hypertension Thyroid disease Depression Anxiety Arthritis Medications Lantus 60 units SQ BID NovoLOG 25 units SQ TIDAC metformin 1000 units PO BIDAC gabapentin 300mg PO TID HCTZ 25mg PO daily diltiazem 180mg PO daily levothyroxine 88mcg PO daily zolpidem 5mg PO QHS prn clonazepam 0.5mg PO QHS prn Tylenol XS 2 tabs PO daily
18. 18. Other Dyslipidemia Recurrent UTIs Psoriasis Asthma (mild) Misc. medications Aspirin 325mg PO daily Vitamin B12 lozenge
19. 19. Objective
20. 20. Vitals Ht: 54 Wt: 250 lbs 122/80 mmHg 121/61 mmHg (11/12/13) HR: 87 bpm A1c 10.7% (10/7/13) 9.1% (4/8/13) Lipids (10/7/13) TC: 166 mg/dL TG: 199 mg/dL LDL : 90 mg/dL HDL: 36 mg/dL BMI = 42.89
21. 21. Na 139 mg/dL K 3.8 mg/dL Cl 98 mg/dL CO2 28 mg/dL Ca 9.5 mg/dL TSH 2.267 mcg/L SCr 0.81 mg/dL BUN 13 mg/dL CrCL 60 mL/min eGFR 74.84 mL/min/1.73m2
22. 22. P. Jones & I. Idris
23. 23. Review article 10 retrospective case series P. Jones & I. Idris. The use of U-500 regular insulin in the management of patients with obesity and insulin resistance. Diabetes, Obesity and Metabolism. 2013.
24. 24. Recommends initiation of U-500 when total daily dose of insulin is >200 units Reduce TDD by 10-20% May give in 2-4 injections BID: 60% a.m. and 40% p.m. TID: 40/30/30, 45/35/20, 40/40/20 QID: 30/30/30/10 Lane WS et al. High-dose insulin therapy: is it time for U-500 insulin?. Endocr Pract. 2009. Lane WS. Use of U-500 regular insulin by continuous subcutaneous insulin infusion in patients with type 2 diabetes and severe insulin resistance. Endocr Pract.2006.
25. 25. Mean reduction in A1c of 1% Reduction in number of injections Weight gain Improved quality of life Reduction in cost Increase in total insulin dose No significant difference in combination of oral medications and U-500 compared to those not taking oral medications P. Jones & I. Idris. The use of U-500 regular insulin in the management of patients with obesity and insulin resistance. Diabetes, Obesity and Metabolism. 2013.
26. 26. Suzanne L. Quinn, M.D., M. Cecilia Lansang, M.D., and Deanna Mina, Pharm.D.
27. 27. To assess the safety and effectiveness of highly concentrated U-500 regular insulin in patients with insulin-resistant type 2 diabetes mellitus who were switched from U-100 insulin. Methods Retrospective cohort study Inclusion 21 patients aged 41-81 y/o with poorly controlled DM and insulin resistance that were referred to the clinic between 7/1/07- 6/30/08 The duration of diabetes was highly variable, ranging from 222 yrs, with an average duration of 9.1 5.7 years. Primary outcome Reduction in A1c Secondary outcomes Reduction in number of daily insulin injections, daily insulin dose (units/day)and body weight Suzanne QL et al. Safety and Effectiveness of U-500 Insulin Therapy in Patients with Insulin-Resistant Type 2 Diabetes Mellitus. Pharmacotherapy. 2011.
28. 28. Response to U-500 Regular Insulin in the 21 Patients Variable Before U-500 Insulin After U-500 Insulin Change p-value Hemoglobin A1c (%) 9.5 1.3 7.7 1.6 1.7