1. Hyperglycemia in the Hospital: Subcutaneous Regimens Arizona ACP – Chapter Meeting Cheryl.O’Malley@bannerhealth.com November 5, 2006

2. SHM Glycemic Control Workgroup Greg Maynard-UCSD Maryann Emmanuele – Loyola Irl Hirsh- Univ of Wash Robert Rushakoff- UCSF Susan Braithwaithe- UNC Andrew Ahmann-OHSU Michelle Magee- Nathanial Clark- ADA David Wesorick – Univ of Michigan Kevin Larson-HCMC Jeff Schnipper-Brigham and Women’s Case Management, Pharmacy and Nursing representatives ACP, AACE, ACE, and ADA representatives

3. Hospital Costs Account for Majority of Total Costs of Diabetes Hogan P, et al. Diabetes Care. 2003;26:917 – 932. Per Capita Healthcare Expenditures (2002) DiabetesWithout diabetes

4. Hyperglycemia*: A Common Comorbidity in Medical-Surgical Patients in Hospitals 64% ) ( 1.7% mortality) 12% (16% mortality) 26% 3% mortality Normoglycemia Known Diabetes New Hyperglycemia Umpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002 n = 2,020 * Hyperglycemia: Fasting BG  126 mg/dl or Random BG  200 mg/dl X 2 or Random BG  200 mg/dl X 2

5. Relationship between inpatient and outpatient diabetes management Inpatient Compliance with glycemic goals depends on physicians, nursing and hospital staff Outpatient Compliance with glycemic goals depends on the patient Lessons learned in the hospital can impact patient self care behavior at home Care received in the outpatient setting can affect need for hospitalization

6. Landmark trials favoring tight glycemic control for inpatients and outpatients Inpatient DIGAMI (1997) van den Berghe (2001): IV insulin in SICU Outpatient DCCT UKPDS

7. First DIGAMI: Insulin Therapy Improves Outcomes in Patients with MI IV insulin in AMI X 24 hours Then subcutaneous for 3 months Target glucose 126-180mg/dL 29% reduction in mortality- 1 year 28% reduction in mortality- 3.4 year

8. Intensive Insulin Therapy in Critically Ill Surgical Patients: Morbidity and Mortality Benefits van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367. Reduction (%) MortalitySepsisDialysisPolyneuropathy Blood Transfusion 34% 46% 41% 44% 50% N = 1,548

9. What do the experts say? ICUNon-ICU Preprandial Non-ICU Maximal AACE/ACE ADA 110 mg/dL 100 mg/dL 110 mg/dL 90-130 mg/dL 180 mg/dL

10. Achieving these goals is not easy!

11. Sliding Scale Alone Doesn’t Work Sliding scale prospective cohort study Patients treated solely with SSI were 3X more likely to have BG>300 In 80% of patients, the orders written at admission were never changed despite poor control Quele et al, Arch Intern Med 1997: 157; 545-552

12. Oral Agents in the Hospital Sulfonylureas –Hypoglycemia (long acting) Metformin –Lactic acidosis risk =renal insufficiency, hypotension, CHF –GI (nausea, abd. pain, diarrhea) Thiazoladinediones (TZDs) or “glitazones” –Possible liver toxicity –Fluid overload, CHF –Inability to titrate (very slow onset of action) –Only pioglitazone approved for use with insulin

13. Indications for IV Insulin Therapy Prolonged fasting (>12 h) in type 1 DM Critical illness Before major surgical procedures After organ transplantation DKA Labor and delivery Acute MI Other illnesses requiring prompt glucose control ACE Position statement on inpatient diabetes 2004

14. Insulin (µU/mL) Glucose (mg/dL) Physiologic Insulin Secretion 150 100 50 0 789101112123456789 A.M.P.M. Basal Glucose Time of Day 50 25 0 Breakfast Lunch Supper Normal 24-Hour Profile Prandial Glucose 1. Nutritional Insulin 2. Basal Insulin: Suppresses Glucose Production Between Meals And Overnight

15. Insulin Requirements in Health and Illness Clement S, et al. Diabetes Care. 2004;27:553–591. Reprinted with permission. Units HealthySick/EatingSick/NPO Correction Nutritional Prandial Basal

16. Methods to estimate the total daily dose of insulin (TDDI) 1.Based on the amount required by insulin infusion 2.Adding up the total dose of insulin used in the patient’s home regimen 3.Calculating the dose based on weight and body habitus 0.3 units/kg if on dialysis, very lean, or has hypoglycemia risk factors 0.4 units/kg standard patient with normal habitus 0.5 units/kg if BMI 25-30 0.6 units/kg if BMI >30, high dose steroids or known high degree of insulin resistance

17. Hirsch, I. B. N Engl J Med 2005;352:174-183 Approximate Pharmacokinetic Profiles of Human Insulin and Insulin Analogues

18. Distribution of Scheduled Basal vs. Nutritional Insulin 40-50% should generally be basal Remaining 50-60% divided evenly and given to cover nutritional intake –If the nutritional intake is interrupted, or severely reduced, this portion of insulin must be proportionately reduced.

19. Specific Situations

20. Eating Regular Meals Basal: 50% of TDDI –Long acting at bedtime or morning –Intermediate bid (50/50 or 2/3 am and 1/3 pm) or at bedtime –Insulin drip Prandial/Nutritional: 50% of TDDI OR based on carbohydrate counting –Rapid acting before breakfast, lunch and dinner –Regular before breakfast and dinner +/- lunch Correction –Rapid acting or regular before meals +/- bedtime

21. Not Eating Basal: 50% of TDDI –Long acting at bedtime or morning –Intermediate bid (50/50 or 2/3 am and 1/3 pm) or at bedtime  Reduce dose by ½ to 1/3 –Insulin drip (preferred if prolonged NPO, ICU or ketosis prone) Prandial/Nutritional: N/A Correction –Rapid acting every 4 hours –Regular every 6 hours

22. NPO = Hold scheduled “meal” insulin AND give basal and supplemental Plasma Glucose (mg/dL) 200 100 0 06001200 Time of Day 180024000600 150 250 50 Glucose Glargine (Lantus) Rapid Acting meal/Prandial 30 units 1 unit 3 units 10 units Hold “meal” insulin

23. NPO = Reduce the dose of NPH by ½ or 1/3 due to the peak Plasma Glucose (mg/dL) 200 100 0 06001200 Time of Day 180024000600 150 250 50 Glucose NPH Rapid Acting meal/Prandial 1 unit 3 units 10 units Hold “meal” insulin

24. Continuous Enteral Tube Feeds Basal: Less than or equal to 50% of TDDI –Long acting at bedtime or morning –Intermediate divided equally bid or tid –Insulin drip Prandial/Nutritional: 50% of TDDI –Rapid acting every 4 hours –Regular every 6 hours Alternative of prandial + basal together –70/30 divided equally q 6-8 hours Correction –Rapid acting every 4 hours –Regular every 6 hours

25. Bolus Tube Feeds Basal: 50% of TDDI –Long acting at bedtime or morning –Intermediate bid (50/50 or 2/3 am and 1/3 pm) or at bedtime –Insulin drip Prandial/Nutritional 50% of TDDI –Rapid acting with each tube feeding –Regular before each tube feeding Correction –Rapid acting every 4 hours –Regular every 6 hours

26. Night time tube feeds Monitor blood sugars every 4 hours for the first few nights with supplemental scale coverage. After the dosing is determined –Give a short acting insulin at the start of the tube feeds to cover the first several hours along with NPH to cover the rest of the night.

27. Total Parenteral Nutrition Basal/Prandial together: –Insulin drip separate from TPN –Regular insulin added to TPN bags (80% of TDDI) –70/30 q 8 hours* Correction –Rapid acting every 4 hours –Regular every 6 hours

28. Transitioning from IV insulin Calculate the avg insulin infusion rate in a steady state over the last 6 hours Multiply this by 20 (this is about 80% of the total in the last 24 h) –If substantial nutrition was provided during this time period, then the amount calculated represents the TDDI –If insignificant nutritional intake was taking place, this amount equals the basal dose

29. High dose glucocorticoids Basal: 30% of TDDI –Intermediate bid (50/50 or 2/3 am and 1/3 pm) or at morning only –Insulin drip –Long acting at bedtime or morning Prandial/Nutritional: 70% of TDDI –Rapid acting before breakfast, lunch and dinner –Regular before breakfast and dinner +/- lunch –RA or Regular every 4-6 hours if NPO Correction –Rapid acting or regular before meals +/- bedtime or –Every 4-6 hours if NPO

30. Correction Dose Scales Low dose <40 units/d Medium dose 41-80 units/d High dose >80 Units/d Premeal BG Lispro/Aspart Insulin 120-170 1 unit 3 units 171-220 2 units 3 units 5 units 221-270 3 units 5 units 7 units 271-320 4 units 7 units 9 units >320 5 units 9 units 11 units

31. Calculating the Correction Factor 1700/TDD= the amount that one unit of insulin will lower the blood sugar

32. Responding to hypoglycemia Were they symptomatic? Did they get the insulin amount as ordered? Did they eat within 15 minutes of getting their rapid acting insulin? Did they get bedtime rapid acting insulin to cover a blood sugar without eating? Have they had a recent change in their nutrition—tube feeds turned off, advancing po? If none of these, decrease TDDI

33. Investigate Hyperglycemia Were they low at some point and insulin held  should still be given just decreased dose NPO at some point and insulin was held? Were the correct doses given (pre-meal + supplemental) Are they getting dextrose containing fluids? Increase your doses

34. Adjust Doses Daily Add up ALL of the insulin given in the last 24 hours this was the real TDDI If some were over 180 mg/dL and none less than 80 then –Add 10% to the TDDI from the prior day If some were less than 80 and no other cause –Decrease the TDDI by 20% Redivide the new TDDI to preserve the desired ratio

35. Discharge Planning for New Hyperglycemia Check HgbA1C: –>6% highly likely to have DM –<5.2% unlikely to have DM –5.2-6% indeterminate Need close follow up –Fasting blood glucose or OGTT –Consider home blood glucose testing Refer patients for diabetes education with follow-up education Greci, et al. Diabetes Care April 2003 26; 1064-1068

36. Admission HbA1C Helpful If pre-admission control acceptable go back to home regimen If HbA1C>8% on maximum oral agents, probably needs basal insulin Discharge Planning for Patients with Known Diabetes

37. Starting Outpatient Basal Insulin at Discharge Continue oral agent(s) at same dosageContinue oral agent(s) at same dosage Add a single, bedtime insulin doseAdd a single, bedtime insulin dose –NPH –Glargine (bedtime or am) Increase insulin dose as needed to achieve FBS<110mg &/or HbA1C <Increase insulin dose as needed to achieve FBS<110mg &/or HbA1C < 7% Diabetic teaching

38. How Are We Doing? 1/3 of your patients with hyperglycemia have a mean glucose of >200 mg/dL 60% will remain on a static regimen of sliding scale only insulin 10% of your patients will have at least one hypoglycemic event Nursing and medical staff are unevenly educated Discharge plans will include follow-up of hyperglycemia only a minority of time Umpierrez and Maynard J Hosp Med 2006

39. “Insanity: Doing the same thing over and over again and expecting different results” – Albert Einstein

40. Steps Toward Avoiding Hypoglycemia Physiologic insulin dosing regimens Standardize order sets with built in orders of when to hold or reduce insulin doses Multidisciplinary team Lots of education! (nurses, mds, etc)

41. Summary Focus has shifted recently toward the importance of glucose management in hospitalized patients Use a physiologic regimen for insulin It is most important to work within the framework of your institution Review glucose results and adjust daily Make glucose control and diagnosis of diabetes part of your d/c planning Still quite a bit of study needed

42. http://www.hospitalmedicine.org/

44. Essential Guidelines and Reviews ACE Position Statement and Consensus Conference Reviews –Garber AJ, Moghissi ES, Bransome ED Jr, et al. American College of Endocrinology Position Statement on Inpatient Diabetes and Metabolic Control. Endocr Pract. 2004;10 Suppl 2:4-9. –Magee MF, Clement S. Subcutaneous insulin therapy in the hospital setting: issues, concerns, and implementation. Endocr Pract. 2004;10 Suppl 2:81-8. –Bode BW, Braithwaite SS, Steed RD, Davidson PC. Intravenous insulin infusion therapy: Indications, methods, and transition to subcutaneous insulin therapy. Endocr Pract. 2004;10 Suppl 2:71-80. ACE / ADA Inpatient Diabetes and Glycemic Control Consensus Statement –Garber A, Moghissi E, Buonocore D, Clark N, Cobin R, Eckel R, Fleming B, Fonseca V, Haas L, Inzucchi S, Kelemen M, Korytkowski M, Maynard G, Newton C, Peeples M. American College of Endocrinology and American Diabetes Association Consensus statement on inpatient diabetes and glycemic control: a call to action. Diabetes Care. 2006 Aug;29(8):1955-62. also published in Endocrine Practice. 2006 July / Aug 12 (4) 458-68. ADA Technical Review –Clement S, Braithwaite SS, Magee MF et al; American Diabetes Association Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-91. ADA Standards for Diabetes –American Diabetes Association: Standards of Medical Care in Diabetes. Diabetes Care. 2006”29(Suppl. 1): S4-S42. ASHP Recommendations for Safe Use of Insulin in Hospitals –American Society of Health-System Pharmacists and the Hospital and Health-System Association of Pennsylvania: Recommendations for Safe Use of Insulin in Hospitals. Accessed as pdf at: http://www.ashp.org/emplibrary/Safe_Use_of_Insulin.pdf

45. Hyperglycemia in Medical / Surgical Wards Leahy JL Insulin management and diabetic patients on general medical and surgical floors Endocrine Practice 2006; 12, supp 3 86-90 Umpierrez GE, Isaacs SD, Bazargan N, et al. Hyperglycemia: an independent marker of in- hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87:978– 982. Fonseca, V Newly Diagnosed Diabetes/ Hyperglycemia in Hospitals: What should we do? Endocrine Practice 2006; 12; supp 3: 108-111 Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia as a prognostic indicator in trauma. J Trauma. 2003;55:33-8. Capes SE, Hunt D, Malmberg K Pathak P, et al. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001;32:2426-2432. Golden S, Peart -Vigilance C Kao W, et al. Perioprerative glycemic conrol and risk of infectious complications in a cohort of adult with diabetes. Diabetes Care 1999;22:1408-1414. Khaw KT, Wareham N, Luben R, et al. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ. 2001;322:1-6 Levetan CS, Passaro M, Jablonski K, Ratner RE. Unrecognized diabetes among hospitalized patients. Diabetes Care.1998;21:246-249. Pomposelli JJ, Baxter JK, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenter Enteral Nutr. 1998;22:77-81. Weiser et al. Cancer 2004 Mar 15;100(6):1179-85. Mathew et al. Early peri-operative glycemic control and allograft rejection in patients with DM: a pilot study.Transplantation 2001 Oct 15;72(7):1321-4