Achieving Glycemic Control in the Hospital Setting (Part 3 of 4)

Recommendations for Managing Patients With Diabetes in the Hospital Setting Review as stated

IV Insulin in the ICU Setting Antihyperglycemic Therapy Insulin Recommended OADs Not generally recommended IV Insulin in the ICU Setting In the hospital setting, insulin therapy is the recommended method for glycemic control For critically ill patients, IV insulin is the preferred route of administration Subcutaneous dosing of insulin is recommended for noncritically ill patients The role of oral antidiabetic agents is limited in the hospital setting Reference Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control. Diabetes Care. 2009;32(6):1119-1131. IV Insulin Critically ill patients in the ICU SC Insulin Noncritically ill patients Moghissi ES et al. Diabetes Care. 2009;32(6):1119-1131.

IV Insulin Protocols Multiple published protocols are available that are effective and safe. Some examples include: Yale1 Markovitz2 Leuven3 Portland4 Texas Diabetes Council5 DIGAMI6 University of Washington7 Krinsley8 Rush University Protocol9 Northwestern University10 IV Insulin Protocols There are several published insulin protocols available. The exact protocol is probably less important than its presence in an institution, adaptation to the individual hospital, adequate buy-in from key local opinion leaders and implementation staff, and ultimate validation References Goldberg PA, Siegel MD, Sherwin RS, et al. Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care. 2004;27(2):461-467. Markovitz LJ, Wiechmann RJ, Harris N, et al. Description and evaluation of a glycemic management protocol for patients with diabetes undergoing heart surgery. Endocr Pract. 2002;8(1):10-18. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345(19):1359-1367. Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. Endocr Pract. 2004;10(suppl 2):21-33. Texas Diabetes Council. Available at: http://www.dshs.state.tx.us/diabetes/pdf/algorithms/iv%20insulin%20infusion.pdf. Malmberg K, Norhammar A, Wedel H, Rydén L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation. 1999;99(20):2626-2632. Ku SY, Sayre CA, Hirsch IB, Kelly JL. New insulin infusion protocol improves blood glucose control in hospitalized patients without increasing hypoglycemia. Joint Commission J Quality Patient Safety. 2005;31(3):141-147. Krinsley J. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79(8):992-1000. Donaldson S, Villanuueva G, Rondinelli L, Baldwin D. Rush University guidelines and protocols for the management of hyperglycemia in hospitalized patients: elimination of the sliding scale and improvement of glycemic control throughout the hospital. Diabetes Educ. 2006;32:954-962. DeSantis AJ, Schmeltz LR, Schmidt K, et al. Inpatient management of hyperglycemia: the Northwestern experience. Endocr Pract. 2006;12(5):491-505. 1. Goldberg PA et al. Diabetes Care. 2004;27(2):461-467; 2. Markovitz LJ et al. Endocr Pract. 2002;8(1):10-18; 3. Van den Berghe G et al. N Engl J Med. 2001;345(19):1359-1367; 4. Furnary AP et al. Endocr Pract. 2004;10(suppl 2):21-33; 5. Texas Diabetes Council. Available at: http://www.dshs.state.tx.us/diabetes/pdf/algorithms/iv%20insulin%20infusion.pdf; 6. Malmberg K et al. Circulation. 1999;99(20):2626-2632; 7. Ku SY et al. Joint Commission J Quality Patient Safety. 2005;31(3):141-147; 8. Krinsley J. Mayo Clin Proc. 2004;79(8):992-1000; 9. Donaldson S et al. Diabetes Educ. 2006;32:954-962; 10. DeSantis AJ et al. Endocr Pract. 2006;12(5):491-505.

Considerations When Converting From IV to Subcutaneous Insulin Initial doses of scheduled subcutaneous insulin are based on previously established dose requirements1 75%-80% of the total daily IV infusion dose is proportionally divided into basal and prandial components2 Subcutaneously administered insulin must be given before discontinuation of IV insulin therapy in order to prevent hyperglycemia2 Intermediate- or long-acting insulin must be injected subcutaneously 2 to 3 hours before discontinuing the IV insulin infusion1 A short- or rapid-acting insulin should be given subcutaneously 1-2 hours before discontinuation of the IV insulin infusion1 Considerations When Converting From IV to Subcutaneous Insulin Review as stated References Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-591. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4):353-369. 1. Clement S et al. Diabetes Care. 2004;27:553-591; 2. Moghissi ES et al. Endocr Pract. 2009;15(4):353-369.

SC Insulin Is Appropriate for Noncritically Ill Patients Antihyperglycemic Therapy Insulin Recommended OADs Not generally recommended SC Insulin Is Appropriate for Noncritically Ill Patients [Slide used to introduce subcutaneous insulin section] Reference Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32(6):1119-1131. IV Insulin Critically ill patients in the ICU SC Insulin Noncritically ill patients Moghissi ES et al. Diabetes Care. 2009;32(6):1119-1131.

Overview of Subcutaneous Insulin Preferred method for achieving and maintaining glucose control in non–ICU patients with diabetes or stress hyperglycemia Effective insulin therapy must contain basal, nutritional, and supplemental (correction) components to achieve target goals Supplemental-dose insulin is the use of additional short- or rapid-acting insulin in conjunction with scheduled insulin doses to treat blood glucose levels above desired targets Prolonged therapy with sliding-scale insulin alone is ineffective in the majority of patients and potentially dangerous in those with type 1 diabetes Overview of Subcutaneous Insulin Review as stated Reference Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4):353-369. Moghissi ES et al. Endocr Pract. 2009;15(4):353-369.

The Basal-Bolus Principle: Adding Mealtime Control Rapid-acting insulin analog Long-acting insulin analog Insulin level The Basal-Bolus Principle: Adding Mealtime Control The basal-bolus principle is the concept of using a long-acting insulin for basal (FPG) control, as well as a rapid-acting insulin to cover mealtime (PPG) control 0:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 0:00 Time of day Theoretical representation of insulin profiles

RABBIT 2: Glycemic Control With Basal-Bolus vs Sliding-Scale Insulin N=130 insulin-naïve hospitalized nonsurgical patients with T2DM n=9 with BG >240 mg/dL 240 220 200 180 160 140 120 100 1 Admit 2 3 4 5 6 7 8 9 10 † * 300 Switched from sliding-scale to basal-bolus insulin Sliding-scale 260 220 Blood glucose (mg/dL) 180 RABBIT 2: Glycemic Control With Basal-Bolus vs Sliding-Scale Insulin Basal-bolus regimens have an important advantage over sliding-scale regimens: they are proactive Umpierrez et al randomized 130 insulin-naïve hospitalized nonsurgical patients to 1 of 2 insulin regimens: Long-acting insulin (glargine) given once daily with supplemental rapid-acting insulin (glulisine). Patients were started at a total daily dose of 0.4 unit/kg if BG levels were 140-200 mg/dL or 0.5 unit/kg if BG levels were 201-400 mg/dL. One-half of the total daily dose was given as long-acting insulin Regular insulin administered 4 times daily according to a sliding scale for glucose levels >140 mg/dL The goal of insulin therapy was to maintain fasting and premeal BG levels <140 mg/dL while avoiding hypoglycemia (BG <60 mg/dL) As shown, the basal-bolus regimen achieved better glycemic control than the sliding-scale regimen. Hypoglycemia occurred in 2 patients in each group Compared with the sliding-scale regimen, the basal-bolus regimen was associated with lower mean fasting glucose (147 vs 165 mg/dL, P<.01), lower mean random glucose (164 vs 188 mg/dL, P<.001), and lower mean glucose during hospital stay (166 vs 193 mg/dL, P<.001) (data not shown) RABBIT 2=Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes Reference Umpierrez GE, Smiley D, Zisman A, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30(9):2181-2186. 140 Basal-bolus‡ 100 Admit 1 2 3 4 1 2 3 4 5 6 7 Days of therapy *P<.01; †P<.05; ‡Long-acting insulin (glargine) once daily + short-acting insulin (glulisine) before meals, total dose 0.4 unit/kg (BG 140-200 mg/dL) or 0.5 unit/kg (BG 201-400 mg/dL). RABBIT 2=Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes. Umpierrez GE et al. Diabetes Care. 2007;30:2181-2186.

Estimating SC Insulin Dose Model From a Tertiary Care Center To calculate the estimated total daily dose of insulin: T2DM: 0.5-0.7 unit/kg T1DM or type unknown: 0.3-0.5 unit/kg The total daily dose of insulin is then divided into 50% basal (insulin detemir or glargine) and 50% prandial (insulin aspart, lispro, or glulisine) The prandial insulin dose is divided into 3 equal doses that are given with meals Estimating SC Insulin Dose These estimations are recommended for patients when no intravenous insulin therapy has been given Reference DeSantis AJ, Schmeltz LR, Schmidt K, et al. Inpatient management of hyperglycemia: the Northwestern experience. Endocr Pract. 2006;12(5):491-505. DeSantis AJ et al. Endocr Pract. 2006;12(5):491-505.

From the ADA Diabetes in Hospitals Writing Committee Therapeutic Options for Glycemic Control in the Medical or Stabilized Surgical Patient From the ADA Diabetes in Hospitals Writing Committee Patient Status Basal Insulin Needs Nutritional or Prandial Insulin Needs Supplemental-Dose Insulin Needs Eating meals Intermediate-acting insulin twice daily or at bedtime Long-acting insulin analog once daily Insulin infusion Regular insulin 30-45 minutes before meals Rapid-acting insulin analog 0-15 minutes before meals Regular or rapid-acting insulin before meals and/or at bedtime as needed Not eating meals Not applicable Regular insulin every 4-6 hours Rapid-acting insulin analog every 4 hours Enteral tube feeding Intermediate-acting insulin twice daily Long-acting insulin analog at bedtime or in morning Daytime only: Intermediate-acting insulin in morning Therapeutic Options for Glycemic Control in the Medical or Stabilized Surgical Patient The chart illustrates recommendations for glycemic control in a variety of scenarios. Consideration must be given to basal, nutritional/prandial, and supplemental-dose needs Review as stated Reference Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591. Appendix 1. Clement S et al. Diabetes Care. 2004;27(2):553-591.

From the ADA Diabetes in Hospitals Writing Committee Subcutaneous Insulin Can Be Augmented With Premeal Supplemental-Dose Insulin From the ADA Diabetes in Hospitals Writing Committee Sample algorithm (worksheet) for supplemental-dose insulin to be administered in addition to scheduled basal and nutritional insulin to correct premeal hyperglycemia Additional Insulin Premeal BG (mg/dL) Low Dose Medium Dose High Dose Individualized 150-199 1 unit 2 units 200-249 3 units 4 units 250-299 5 units 7 units 300-349 10 units >349 8 units 12 units Subcutaneous Insulin Can Be Augmented With Premeal Supplemental-Dose Insulin This is a sample algorithm (worksheet) for supplemental-dose insulin based on total daily insulin requirements Reference Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591. Online Appendix 1. Low dose: for patients requiring <40 units/day Medium dose: for patients requiring 40-80 units/day High dose: for patients requiring >80 units/day Clement S et al. Diabetes Care. 2004;27(2):553-591. Online Appendix 1.

Potential Problems With Use of Sliding-Scale Insulin Regimens Sliding-scale insulin usually consists of regular insulin given alone This technique has been shown to be ineffective for the following reasons: Reactive approach can lead to rapid swings in blood glucose, resulting in hyperglycemia and hypoglycemia Admission regimen is likely to be used throughout hospitalization without appropriate modification It treats hyperglycemia after the fact instead of proactively anticipating need Hazards of sliding-scale insulin use exceed the advantages of its convenience Potential Problems With Use of Sliding-Scale Insulin Regimens The traditional sliding-scale insulin regimens consisting solely of regular insulin are ineffective for the reasons stated Reference American Diabetes Association. Standards of Medical Care in Diabetes–2006 (Position Statement). Diabetes Care. 2006;29(suppl):S4-S42. ADA. Diabetes Care. 2006;29(suppl):S4-S42.

Current Guidelines on the Use of Sliding-Scale Insulin American Diabetes Association Sliding-scale regimen prescribed on admission is likely to be used throughout the hospital stay without modification, even when control remains poor1 American Association of Clinical Endocrinologists Sliding-scale regimens are ineffective and potentially harmful when used alone2 American Medical Directors Association Sliding-scale is generally not recommended in long-term care facilities, as it is neither effective nor efficient in the inpatient setting3 Current Guidelines on the Use of Sliding-Scale Insulin Review as stated References American Diabetes Association. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33(suppl 1):S11-S61. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):3-68. American Medical Directors Association. Diabetes Management in the Long-term Care Setting: Clinical Practice Guideline. Columbia, MD: American Medical Directors Association; 2008. American Diabetes Association. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33(suppl 1):S11-S61. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):3-68. American Medical Directors Association. Diabetes Management in the Long-term Care Setting: Clinical Practice Guideline. Columbia, MD: American Medical Directors Association; 2008.