Inpatient Diabetes Management

1. Inpatient Diabetes Management Ananda Nimalasuriya April 2010

2. Objectives • Update diabetes prevalence data • Inpatient hyperglycemia observations • Inpatient diabetes management studies • ADA/AACE recommendations

3. CDC Diabetes Fact Sheet 2010 • Newest data, released January 26, 2011 • Diabetes affects 25.8 million people • 8.3% of the U.S. population • DIAGNOSED18.8 million people • UNDIAGNOSED7.0 million people

4. New Hyperglycemia: An Independent Marker of In-Hospital Mortality 31%* 30 20 10 0 ICU Mortality Mortality (%) 11% 10% Normoglycemia Known New Diabetes Hyperglycemia *P<0.01 Umpierrez et al. J Clin Endocrinol Metab 87:978, 2002

5. Hyperglycemia: An Independent Marker of ICU Mortality in Patients without known diabetes Krinsley, JS. Mayo Clin Proc. 2003;78:1471-1478

6. New Hyperglycemia: An Independent Marker of In-Hospital Mortality 30 20 10 0 Total Inpatient Mortality Mortality (%) 16%* 3.0% 1.7% Normoglycemia Known New Diabetes Hyperglycemia *P<0.01 Umpierrez et al. J Clin Endocrinol Metab 87:978, 2002

7. Stress Hyperglycemia Counterregulatory hormones • Cortisol • Epinephrine • Glucagon • Growth Hormone +  Glucose Production FFAs Glucose FFAs  Glucose Utilization FFAs  Lipolysis Metchick LN et al. Am J Med 113:317, 2003 Mizrock et al, Am J Med 1995 Kitabchi AE et al. Diab Care 24:131, 2001

8. Hyperglycemia in the Hospital 1034 Hospitalized Patients 130 (13%) with BG >200 mg/dl DM as 1° Dx = 15 (12%) DM as 2° Dx = 115 (88%) Known h/o DM 74 (56%) Unrecognized DM 41 (32%) Levetan CS et al. Diab Care 21:246, 1998

9. Hyperglycemia in the Hospital Diabetes undiagnosed before or at admission in 41/130 of patients with glucose >200 mg/dL • 54% received insulin • 59% received bedside glucose monitoring • Only 33% of progress notes documented hyperglycemia • Only 7.3% (3 patients) documented diabetes as a possible diagnosis Levetan CS et al. Diab Care 21:246, 1998

10. 2008 ADA/AACE Inpatient Diabetes Clinical Practice Recommendations • All patients with diabetes admitted to the hospital should havetheir diabetes clearly identified in the medical record. (E) • All patients with diabetes should have an order for bloodglucosemonitoring, with results available to all members ofthe healthcare team. (E) American Diabetes Assoc. Clinical Practice Recommendations 2008, Diabetes Care, January 2008

11. 2009 ADA/AACE Inpatient Diabetes Clinical Practice Recommendations • All patients with diabetes admitted to the hospital should have an A1C obtained if the result of testing in the previous 2–3 months is not available. (E) • A diabetes education plan including “survival skills education” and follow-up should be developed for each patient. (E) • Patients with hyperglycemia in the hospital who do not have a diagnosis of diabetes should have appropriate plans for follow-up testing and care documented at discharge. (E) American Diabetes Assoc. Clinical Practice Recommendations 2009, Diabetes Care, January 2009

12. Controlling Hyperglycemia in the Hospital – What’s the evidence? • Observational studies correlate hyperglycemia with adverse outcomes • Case-control studies show reduction in surgical site infections, length of stay • RCTs in select patient populations followed

13. Normoglycemia in IntensiveCare Evaluation– Survival Using Glucose Algorithm Regulation(NICE-SUGAR) • RCT multicenter (42 hospitals) trial • 6104 patients randomized to • tight control(81-104 mg/dL), using insulin infusion • standard control (<180) using insulin infusion • 20% with diabetes at admission • Mean fasting blood glucose of 144 N Engl J Med. 2009 Mar 26;360(13):1283-97.

14. Data on Blood Glucose Level, According to Treatment Group The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297

15. NICE-SUGAR VariableConventionalIntensive (N=3012)(N=3010) 28 day mortality 627 630 3 Month mortality 751 829 Severe Hypoglycemia 0.5% 6.8% • All other outcome measures and adverse effects similar beteween groups ARRRRR NS NS -2.6 -10.6

16. ADA/AACE after NICE-SUGAR • NICE-SUGAR…should NOT lead to an abandonment of the concept of good glucose management in the hospital setting • The ADA and AACE caution against … providers [becoming] complacent about uncontrolled hyperglycemia http://www.diabetes.org/for-media/2009/joint-statement-from-ada-and.html accessed Nov 25, 2009.

17. Response to NICE-SUGAR • Different target ranges used for conventional group (140-180 mg/dL vs 180-215) • Nonstandardized glucometers may have underestimated hypoglycemia rate • Insulin may be deleterious in hypocaloric feeding used in NICE-SUGAR (enteral only) • Early withdrawal of care (median 6 days) may have biased the studysignificantly more corticosteroid use in intensive group VandenBerhe, et al. NEJM July 2009 vol. 361 no. 1 89-92

18. ADA/AACE: Care of critically ill patients after NICE-SUGAR • insulin infusion should be used to control hyperglycemia in the majority of critically ill patients in the ICU setting, with a starting threshold of no higher than 180 mg/dl (10.0 mmol/l). • Once initiated, the glucose level should be maintained between 140 and 180 mg/dl (7.8 and 10.0 mmol/l) Lower targets may be appropriate is some groups • Have appropriate protocols to limit hyper- and hypoglycemia Diabetes Care June 2009 vol. 32 no. 6 1119-1131

19. Diabetes on the medical/surgical floors How effective is sliding scale insulin? Are there more effective means of controlling blood sugar?

20. Performance of Sliding Scale Insulin Regimens in Diabetic Inpatients Study population: 171 adults with diabetes admitted to an acute care hospital’s Medical Service over a 7-week period Results: 23% of patients experienced hypoglycemia (3.4 episodes per 100 BGs) 40% experienced hyperglycemia (9.8 episodes per 100 BGs) Queale WS et al. Arch Intern Med 157:545, 1997

21. Frequency of Uncontrolled Glucose Levels in diabetic inpatientsTarget 72-162 mg/dL 50 40 30 20 10 0 Medical floor Surgical floor Percent Good control Suboptimal control Poor control (80%+ in target) (40-80% in target) (<40%+ in target) Bhattacharyya A et al. Diabet Med 19:412, 2002

22. Treatment of hyperglycemia:A well designed protocol dampens the blood glucose variability BG levels with sliding scale alone BG levels with infusion or basal, bolus, correction dosing

23. Insulin Action in the nondiabetic

24. Insulin Action: Intensive therapy with Basal + Bolus insulin Bolus Bolus Bolus Basal

25. BBC: Basal, Bolus, Correction Correction Needs- “Sliding scale” Bolus Needs- short acting insulin given with meals based on amount of carbohydrate eaten Basal Needs - long acting insulin THE “NEW” INSULIN PARADIGM

26. Basal-Bolus Insulin Therapy in the Inpatient management of patients with T2DM – RABBIT 2 Trial RCT to evaluate the safety and effectiveness of basal-bolus therapy vs. Sliding Scale insulin • 130 insulin-naïve patients with T2DM • Intervention • Glargine once daily, glulisine before meals at 0.4 or 0.5 Units/kg/day (1/2 as basal, ½ as bolus), with correction dose over 140 mg/dL • Control • SSI: given QAC or Q6h (NPO) for blood sugar over 140mg/dL using “sensitive,”“usual,” or “resistant” scale Umpierrez, et al, Diabetes Care 30:2181-2186, 2007

27. Basal-Bolus Insulin Therapy in the Inpatient management of patients with T2DM – RABBIT 2 Trial p<0.001 p<0.01 p<0.01 p<0.001 Umpierrez, et al, Diabetes Care 30:2181-2186, 2007

28. Basal Bolus Insulin in inpatients: RABBIT 2 Trial Figure 1— Changes in blood glucose concentrations in patients treated with glargine plus glulisine (•) and with SSI ( ). *P < 0.01; ¶P < 0.05. Umpierrez, et al, Diabetes Care 30:2181-2186, 2007

29. Basal Bolus Insulin in inpatients: RABBIT 2 Trial Figure 2— Mean blood glucose concentration in subjects who remained with severe hyperglycemia despite increasing doses of regular insulin per the sliding-scale protocol ( ). Glycemic control rapidly improved after switching to the basal-bolus insulin regimen (•). P < 0.05 Umpierrez, et al, Diabetes Care 30:2181-2186, 2007

30. 2009 ADA/AACE Inpatient Diabetes Clinical Practice Recommendations • Scheduled prandial insulin doses should be appropriately timed in relation to meals and should be adjusted according to point-of-care glucose levels. The traditional sliding-scale insulin regimens are ineffective as monotherapy and are generally not recommended. (C) • Using correction dose or “supplemental” insulin to correct premeal hyperglycemia in addition to scheduled prandial and basal insulin is recommended. (E) American Diabetes Assoc. Clinical Practice Recommendations 2009, Diabetes Care, January 2009

31. Other agents in the hospital? • Metformin – risk of lactic acidosis • Sulfonylureas –hepatic clearance, though can be influenced by renal clearance as well (active metabolites) • Alphaglucosidase inhibitors • Possible hepatitis if highly absorbed • Exenatide – not approved for use with insulin; renally cleared • Pramlintide – potentiates insulin • DPP-IV inhibitors, Liraglutide - Renally cleared, limited clinical experience

32. 2009 ADA/AACE Clinical Practice Recommendations • Noninsulin agents are inappropriate in most hospitalized patients • Continued use of such agents may be appropriate in selected stable patients who are expected to consume meals at regular intervals • Caution must be exercised with use of metformin Diabetes Care June 2009 vol. 32 no. 6 1119-1131

33. Finger stick blood sugar testing is not reliable in certain situation e.g • Hypoperfusion • Anemia and increased hemotocrit • Severe hyperlipedima • anoxia

34. Inpatient Blood Glucose Control:2008 ADA Clinical Practice Recommendations • Fasting <126 mg/ dL • All random glucose <180-200 mg/ dL • Critically ill 110 - 140 mg/ dL American Diabetes Assoc. Clinical Practice Recommendations 2008, Diabetes Care, January 2008

35. Inpatient Blood Glucose control:2009 ADA/AACE Consensus statement • Premeal <140 mg/ dL • All random glucose <180 mg/ dL • Critically ill 140-180 mg/ dL Diabetes Care June 2009 vol. 32 no. 6 1119-1131