Presentation in summer 2009 on the inpatient management of diabetes.

1. Inpatient Management of Hyperglycemia Russell Vinik, M.D. Hospitalist, University of Utah

3. Umpierrez GE et al. J Clin Endocrinol Metab . 2002;87:978-982. Hyperglycemia Is an Independent Marker of Inpatient Mortality in Patients With Undiagnosed Diabetes In-hospital Mortality Rate (%) Newly Discovered Hyperglycemia Patients With History of Diabetes Patients With Normoglycemia P < 0.01 P < 0.01

4. Postoperative Glycemic Control Correlates With Cardiac-Related Mortality * ( P <.001). Furnary AP et al. J Thorac Cardiovasc Surg . 2003;125:1007-1021. Mortality (%) 0.9 1.3 2.3 4.1 6.0 14.5 Average Postoperative Glucose (mg/dL) * * * *

5. Poor Outcomes Correlate With Hyperglycemia After Acute Ischemic Stroke Williams LS et al. Neurology . 2002;59:67-71. Blood Glucose at Admission .015 .07 .15 .018 .009 7.2 ± 0.4 73% 7% 10% 18% 6 ± 0.3 79% 5% 5% 11% Length of stay Discharged to home In-hospital mortality 30-Day mortality 1-Year mortality P value BG  130 mg/dL (n=258) BG <130 mg/dL (n=385) Outcome

7. Hyperglycemia and Poor Outcomes Following Myocardial Infarction Arch Intern Med. 2009;169(5):438-446 In Hospital Mortality (%) Average Post-admission Glucose

9. Intervention Studies

11. Insulin and Sternal Wound Infections Furnary AP et al. Ann Thorac Surg . 1999;67:352-362. 4 3 2 1 0 DSWI (%) 87 88 89 90 91 92 93 94 95 96 97 Year CII Patients with diabetes Nondiabetic patients

12. Insulin and Mortality in CABG patients CII Year Furnary AP Endocr Pract . 2004;10(suppl 2):21-33. Mortality

14. Intensive Insulin in the Critically Ill Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. 100 96 92 88 84 80 0 0 20 40 60 80 100 120 140 160 Intensive treatment Conventional treatment Intensive treatment Conventional treatment Survival in ICU (%) 100 96 92 88 84 80 0 0 50 100 150 200 250 In-Hospital Survival (%) Days After Admission Days After Admission 42.5% reduction in mortality with intensive treatment; P <.04 34% reduction in mortality with intensive treatment; P <.01

15. Benefits of IV Insulin Treatment in Critically Ill Hospitalized Patients Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. Reduction (%) 34% 46% 41% 50% 44%

17. Stamford Project: Improvement in Mortality * *P <.01 compared with control group. † P <.05 compared with control group. † * † Krinsley JS. Mayo Clin Proc . 2004;79:992-1000. Decrease in Mortality With Treatment (%)

18. Leuven II- Intensive Insulin in MICU Patients with expected LOS >3 days Van den Berghe G et al. N Engl J Med. 2006;354;5:449-61 . * p<.05 * * *

19. Intensive Insulin Meta-analysis of 29 Trials 8432 Patients JAMA 2008;300(8):933-44

21. NICE-SUGAR Results Critical Care Med 2008;36:12 1-8

22. How do we use this data to care for our patients?

23. American Diabetes Association 2009* “Standards of Medical Care” Diabetes Care 2009 32;Supp 1:S14-61 Circulation 2008;117;1610-19 Critical Care Med 2008 35:296-327 International Guidelines for Management of Severe Sepsis and Septic Shock: 2008 American Heart Association: Hyperglycemia and Acute Coronary Syndrome The Endocrine Society- Position Statement March 2009 * ADA/AACE statement March 09 promised new guidelines and recommended targets similar to the “conventional” arm of NICE-SUGAR <150 mg/dL 2C Critical E (Expert Consensus) <180-200mg/dL <126 mg/dL Noncritical <140 110 mg/dL Non-Fasting C A Evidence level <140 Critical non-surgical 110 mg/dL Critical surgical Fasting Patients <180 mg/dL 90-140 mg/dL C C Noncritical Critical <144-180 mg/dL Critical

28. Source of Nutrition- Effects on Insulin Secretion Prandial insulin B L D B L D Basal insulin Basal insulin Basal insulin Prandial insulin The Eating Patient Pt. Receiving Continuous Feeds

30. Kinetics of Insulins Regular NPH 0 12 6 18 24 aspart/glulisine/lispro glargine

31. Mimicking Nature With Insulin Basal/Bolus Concept Physiologic Insulin Secretion Insulin (µU/mL) Glucose (mg/dL) 9 B L D 150 100 50 0 7 8 9 10 11 12 1 2 3 4 5 6 7 8 AM PM Time of Day Basal glucose Adapted from Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Co.; 2001:821 50 25 0 24-hr profile Basal insulin

32. Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart Insulin aspart/glulisine/lispro Insulin glargine B D L HS Insulin Effect Adapted from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy . New York, NY: Marcel Dekker Inc.; 2002:87

33. Example: Patient’s Total Daily Insulin Estimate=60 Units 10 units aspart glulisine lispro 10 units aspart glulisine lispro 10 units aspart glulisine lispro 30 units glargine Insulin Effect Adapted from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy . New York, NY: Marcel Dekker Inc.; 2002:87

34. Twice-Daily Split-Mixed Regimens Regular NPH B D L HS B Endogenous insulin Dawn phenomenon Hyperglycemia

35. Example: Patient’s Total Daily Insulin Estimate=60 Units 13 units NPH 27 units NPH 40 units of insulin in the a.m. 20 units of insulin in the p.m. +13 units regular +7 units regular

37. Insulin Requirement During Continuous Dextrose, TPN or Enteral Feedings, or Negligible Carbohydrate Exposure 8 12 6 10

38. Regimens for patient while NPO, on IV’s, or receiving continuous enteral feedings.

40. The Insulin Infusion

43. Peri-Procedural Management 8 12 6 10 Regular NPH Hold short acting insulin and give ½ regular dose of NPH

45. Thank You