2. Inpatient Glycemic Management Patients with Non-Critical illness Approaches and Tools

3. Inpatient Glycemic Management Definition of terms: Hospital hyperglycemia: Any BG > 140 mg/dl (7.8 mmol/L) Stress hyperglycemia: Elevations in blood glucose levels that occur in patients with no prior history of diabetes and A1c levels that are not significantly elevated (<6.5%) A1c values above 6.5 in patients with hyperglycemia suggests a prior history of diabetes Hypoglycemia: Any BG < 70 mg/dl (3.9 mmol/L) Severe hypoglycemia: Any BG < 40 mg/dl (2.2 mmol/L) Definition of terms: Hospital hyperglycemia: Any BG > 140 mg/dl (7.8 mmol/L) Stress hyperglycemia: Elevations in blood glucose levels that occur in patients with no prior history of diabetes and A1c levels that are not significantly elevated (<6.5%) A1c values above 6.5 in patients with hyperglycemia suggests a prior history of diabetes Hypoglycemia: Any BG < 70 mg/dl (3.9 mmol/L) Severe hypoglycemia: Any BG < 40 mg/dl (2.2 mmol/L)

4. What are the Glycemic Goals in Non-Critically Ill Patients? The goal is to identify reasonable, achievable, and safe glucose targets using protocols that are efficacious and minimize risk for hypoglycemia. AACE/ADA Consensus Statement on Inpatient Glycemic Control Diabetes Care 32:1119 2009 Endocrine Practice 15:353 2009

5. Recommended Inpatient Glycemic Targets Maintain fasting and preprandial BG <140 mg/dL (7.8 mmol/L) Modify therapy for BG < 100 mg/dl to avoid risk for hypoglycemia Maintain random BG <180 mg/dL (10 mmol/L) More stringent targets may be appropriate in stable patients with previous tight glycemic control.More stringent targets may be appropriate in stable patients with previous tight glycemic control. Less stringent targets may be appropriate in terminally ill patients or in patients with severe co-morbidities.Less stringent targets may be appropriate in terminally ill patients or in patients with severe co-morbidities. Maintain fasting and preprandial BG <140 mg/dL (7.8 mmol/L) Modify therapy for BG < 100 mg/dl to avoid risk for hypoglycemia Maintain random BG <180 mg/dL (10 mmol/L) More stringent targets may be appropriate in stable patients with previous tight glycemic control.More stringent targets may be appropriate in stable patients with previous tight glycemic control. Less stringent targets may be appropriate in terminally ill patients or in patients with severe co-morbidities.Less stringent targets may be appropriate in terminally ill patients or in patients with severe co-morbidities.

6. 1.ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. Endocrine Practice 2009 2.Diabetes Care. 2009;31(suppl 1):S1-S110. Options for glycemic management Insulin Recommended Insulin Recommended Oral agents Non-insulin injectable medications Not Generally Recommended Oral agents Non-insulin injectable medications Not Generally Recommended SC Insulin Non-critically ill patients SC Insulin Non-critically ill patients Recommendations for Managing Hyperglycemia in the Hospital Setting

7. How can the recommended glycemic goals of non-critically ill patients be achieved in a reasonable and safe manner that minimizes risk for hypoglycemic events? AACE/ADA Consensus Statement on Inpatient Glycemic Control Diabetes Care 32:1119 2009 Endocrine Practice 15:353 2009

8. Considerations with Non-insulin therapies in the hospital Sulfonylureas are a major cause of prolonged hypoglycemia Metformin is contraindicated in patients with decrease renal function, use of iodinated contrast dye, and any state associated with poor tissue perfusion (CHF, sepsis) Thiazolidinediones associated with edema and CHF α glucosidase inhibitors are weak glucose lowering agents Amylin and GLP1 agonists can cause nausea and exert a greater effect on postprandial glucose Time action profiles of oral agents can result in delayed achievement of target glucose ranges in hospitalized patients Sulfonylureas are a major cause of prolonged hypoglycemia Metformin is contraindicated in patients with decrease renal function, use of iodinated contrast dye, and any state associated with poor tissue perfusion (CHF, sepsis) Thiazolidinediones associated with edema and CHF α glucosidase inhibitors are weak glucose lowering agents Amylin and GLP1 agonists can cause nausea and exert a greater effect on postprandial glucose Time action profiles of oral agents can result in delayed achievement of target glucose ranges in hospitalized patients

9. Glycemic Management in the Hospital A suggested approach

10. Glycemic Management Strategies in Non-critically Ill Patients Insulin therapy is preferred strategy Scheduled SQ insulin with basal, nutritional, and correctional components Prolonged therapy with “sliding scale” insulin alone is not recommended Insulin therapy is preferred strategy Scheduled SQ insulin with basal, nutritional, and correctional components Prolonged therapy with “sliding scale” insulin alone is not recommended

11. Physiologic Components of Insulin Therapy Basal insulin glargine (Lantus ® ) NPH detemir (Levemir ® ) The amount of insulin necessary to regulate glucose levels between meals and overnight Nutritional insulin regular (Humulin ® Novolin ® ) lispro (HumaLOG ® ) aspart (NovoLOG ® ) glulisine (Apidra ® ) The amount of insulin required to cover meals, IV dextrose, enteral nutrition, TPN or other nutritional supplements Correctional insulin (Supplemental insulin) Refers to supplemental doses of rapid or short acting insulin given to correct elevations in blood glucose that occur despite use of basal and nutritional insulin. Usually administered before meals together with prandial insulin Basal insulin glargine (Lantus ® ) NPH detemir (Levemir ® ) The amount of insulin necessary to regulate glucose levels between meals and overnight Nutritional insulin regular (Humulin ® Novolin ® ) lispro (HumaLOG ® ) aspart (NovoLOG ® ) glulisine (Apidra ® ) The amount of insulin required to cover meals, IV dextrose, enteral nutrition, TPN or other nutritional supplements Correctional insulin (Supplemental insulin) Refers to supplemental doses of rapid or short acting insulin given to correct elevations in blood glucose that occur despite use of basal and nutritional insulin. Usually administered before meals together with prandial insulin

12. Methods for Managing Hospitalized Non-Critically Ill Patients With Diabetes Non-critically ill patients Basal/bolus therapy (multiple daily injections) NPH with rapid acting insulin analog NPH with regular insulin Long-acting insulin (glargine or detemir) with rapid-acting or regular insulin Insulin pump therapy

13. Rapid acting analog or regular NPH BSLHS Insulin Effect B 6-23 NPH with Rapid Acting Analog or Regular Insulin Correction Insulin can be administered with premeal insulin

14. Initiating Insulin Therapy in the Hospital Adjust according to results of BSGM Adjust dose for NPO status or changes in clinical status Adjust according to results of BSGM Adjust dose for NPO status or changes in clinical status Obtain patient weight in kg Calculate total daily dose (TDD) as 0.2-0.4 units per kg/day Calculate total daily dose (TDD) as 0.2-0.4 units per kg/day Choose the dosing schedule Give 50-60% of TDD as basal insulin Give 40-50% of TDD as bolus (premeal or nutritional) insulin Use Correction Insulin for BG above goal range Choose the dosing schedule Give 50-60% of TDD as basal insulin Give 40-50% of TDD as bolus (premeal or nutritional) insulin Use Correction Insulin for BG above goal range

15. Pharmacokinetics of Insulin Preparations Insulin Onset Peak Duration Lispro/Aspart/ Glulisine 5-15 min 1-2 hours 4-6 hours Regular 30-60 min 2-3 hours 6-10 hours NPH 2-4 hours 4-10 hours 12-18 hours Glargine 2-4 hours Relatively peakless 20-24hours Detemir 2 hours 6-24 hours Relatively peakless

16. Pharmacokinetics of Insulin Preparations Short acting Analog Regular 8 AM6 PMN10 PM Insulin Effect 6-23 8 AM NPH Glargine Detemir

17. 130 nonsurgical insulin-naive patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Randomly assigned to sliding scale insulin (SSI) or a basal-bolus regimen with glargine and glulisine –0.4 units per kg/day for BG 140-200 –0.5 units per kg /day for BG > 200 –50% given as glargine and 50% as glulisine Oral antidiabetic drugs discontinued 2 hypoglycemic events (BG < 60 mg/dl) in each group 130 nonsurgical insulin-naive patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Randomly assigned to sliding scale insulin (SSI) or a basal-bolus regimen with glargine and glulisine –0.4 units per kg/day for BG 140-200 –0.5 units per kg /day for BG > 200 –50% given as glargine and 50% as glulisine Oral antidiabetic drugs discontinued 2 hypoglycemic events (BG < 60 mg/dl) in each group Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial) Umpierrez et al. Diabetes Care. 30:2181 2007

18. *P<.01; † P<.05. 240 – 220 – 200 – 180 – 160 – 140 – 120 – 100 – Admit 1 2 3 4 5 6 7 8 9 10 Days of Therapy Blood Glucose (mg/dL) * * * † † † † SSI Basal-Bolus Blood Glucose (BG) Concentration Over Time for Both Groups Umpierrez et al. Diabetes Care. 2007;30:2181–2186. Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial)

19. Adjusting scheduled insulin regimen If fasting and premeal BG >140 mg/dl, dose of glargine increased by 20% For BG <70 mg/dl, glargine reduced by 20% Adjusting scheduled insulin regimen If fasting and premeal BG >140 mg/dl, dose of glargine increased by 20% For BG <70 mg/dl, glargine reduced by 20% Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial) Umpierrez G et al Diabetes Care. 30:2181 2007

20. Persistent hyperglycemia (BG>240 mg/dl) is common (15%) with SSI therapy Days of Therapy BG, mg/dL 100 120 140 160 180 200 220 240 Admit 1 Sliding-scaleBasal-bolus 260 280 300 3345672421 Rabbit 2 Trial: SSI Resulted in Uncontrolled Hyperglycemia in some Patients Hypoglycemia rate: Basal Bolus Group: BG < 60 mg/dL: 3% BG < 40 mg/dL: none SSRI: BG < 60 mg/dL: 3% BG < 40 mg/dL: none Basal Bolus Group: BG < 60 mg/dL: 3% BG < 40 mg/dL: none SSRI: BG < 60 mg/dL: 3% BG < 40 mg/dL: none Umpierrez GE, et al. Diabetes Care. 2007;30(9):2181-2186.

21. 130 nonsurgical non-critically ill patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Half of patients were receiving insulin prior to admission and received similar outpatient insulin dose in the hospital Randomly assigned to: –Detemir once a day with premeal Aspart 3 times a day –NPH and regular twice a day before breakfast and dinner Dosing –0.4 units per kg/day for BG 140-200 –0.5 units per kg /day for BG > 200 Distribution of insulin –Determir group: 50% given as detemir and 50% as aspart –NPH group: 2/3 given as NPH and 1/3 as regular 130 nonsurgical non-critically ill patients age 18-80 with known type 2 diabetes admitted to noncritical care unit Half of patients were receiving insulin prior to admission and received similar outpatient insulin dose in the hospital Randomly assigned to: –Detemir once a day with premeal Aspart 3 times a day –NPH and regular twice a day before breakfast and dinner Dosing –0.4 units per kg/day for BG 140-200 –0.5 units per kg /day for BG > 200 Distribution of insulin –Determir group: 50% given as detemir and 50% as aspart –NPH group: 2/3 given as NPH and 1/3 as regular Detemir with Aspart vs NPH with Regular Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Umpierrez et al. J Clin Endocrinol Metab. 94:564 2009 DEAN Trial

22. Changes in Mean Daily Glucose BG, mg/dL Duration of Therapy, d Data are means  SEM. Detemir + aspart NPH + regular Basal-bolus regimen: detemir was given once daily; aspart was given before meals. NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM. Basal-bolus regimen: detemir was given once daily; aspart was given before meals. NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM. Umpierrez GE, et al. J Clin Endocrinol Metab. 2009;94(2):564-569. P=NS 100 120 140 160 180 200 220 240 Pre-Rx BG 0123456-10 DEAN Trial

23. Copyright ©2009 The Endocrine Society Umpierrez, G. E. et al. J Clin Endocrinol Metab 2009;94:564-569 Mean BG concentrations in hospitalized patients treated with detemir/aspart or NPH/regular Detemir/Aspart NPH/Regular DEAN Trial NPH/Regular BG < 40 mg/dl: 1.6% BG < 60 mg/dl: 25.4% NPH/Regular BG < 40 mg/dl: 1.6% BG < 60 mg/dl: 25.4% Detemir/Aspart BG < 40 mg/dl: 4.5% BG < 60 mg/dl: 32.8% Detemir/Aspart BG < 40 mg/dl: 4.5% BG < 60 mg/dl: 32.8% B L D HS

24. Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009 DEAN Trial “Treatment with basal/bolus regimen with detemir once daily and aspart before meals results in equivalent glycemic control and no differences in the frequency of hypoglycemia compared to a split-mixed regimen of NPH and regular insulin in patients with type 2 diabetes.” Commentary NPH insulin was administered twice a day in this study Detemir insulin was administered once a day It is possible that detemir insulin may need to be administered twice a day Commentary NPH insulin was administered twice a day in this study Detemir insulin was administered once a day It is possible that detemir insulin may need to be administered twice a day

25. *p-values are from Wilcoxon Two-Sample Test Risk Factors for Hypoglycemia Umpierrez et al, ADA Scientific Meeting, Poster #516 p-value * VariableBG < 60 mg/dlBG < 70 mg/dl Age0.0360.001 Weight0.0270.001 A1C0.5210.658 Creatinine0.0110.002 Enrollment BG0.1660.319 Previous treatment 0.005<.001 Previous insulin Rx <0.001<.001 Treatment group <0.001<.001 DEAN Trial

26. Strategies for Reducing Risk for Hypoglycemia in Non-Critical Care Settings Avoidance of sliding-scale insulin alone Use caution in prescribing oral antihyperglycemic agents Modify outpatient insulin doses in patients treated with insulin prior to admission Avoidance of sliding-scale insulin alone Use caution in prescribing oral antihyperglycemic agents Modify outpatient insulin doses in patients treated with insulin prior to admission Braithwaite SS, et al. Endocr Pract. 2004;10(suppl 2):89-99. Umpierrez GE, et al. Poster 516, ADA Scientific Meeting, 2009

27. Specific Clinical Situations Patients with insulin pumps Patients who use CSII pump therapy in the outpatient setting can continue to use these devices as inpatients provided that they have the mental and physical capacity to do so. Availability of hospital personnel with expertise in CSII therapy is recommended A formal Inpatient Insulin Pump Protocol reduces confusion and treatment variability. Patients with insulin pumps Patients who use CSII pump therapy in the outpatient setting can continue to use these devices as inpatients provided that they have the mental and physical capacity to do so. Availability of hospital personnel with expertise in CSII therapy is recommended A formal Inpatient Insulin Pump Protocol reduces confusion and treatment variability.

28. Inpatient CSII Protocol Noschese ML et al Endocrine Practice 15:415 2009 An insulin pump should NEVER be discontinued without initiation of either subcutaneous or intravenous insulin. If the pump is discontinued for any reason, additional insulin (either IV or subcutaneous) MUST be given 30 minutes prior to discontinuation. Patient is to self-manage insulin pump and nurse is to verify and document all basal rates and bolus doses administered. Insulin pumps must be discontinued for an MRI. If the pump is interrupted for more than one hour, another insulin source needs to be ordered.

29. Inpatient CSII Protocol Noschese ML et al Endocrine Practice 15:415 2009 Patient Attestation I confirm that I have been fully trained on the use of my insulin pump prior to this hospitalization and that Patient Attestation I confirm that I have been fully trained on the use of my insulin pump prior to this hospitalization and that I am capable and willing to manage it independently during my hospital stay. If at any time I feel that I am unable to manage the pump, I will alert my medical team. Requires patient and witness signature If at any time I feel that I am unable to manage the pump, I will alert my medical team. Requires patient and witness signature Bailon RM et al Endocrine Practice 15:25 2009

30. Results of an Inpatient CSII Protocol Noschese ML et al Endocrine Practice 2009;15:415 IDS + IPP IPP No IDS/IIP N (%F) 34(32) 12(50) 4(75) Age 48 ± 15 51 ± 16 36 ± 12 LOS (days) 9.8 ± 15.4 5.2 ± 6.2 3 ± 1.5 CSII use (days) 5.4 ± 7.1 3.2 ± 2.9 3 ± 1.5 Mean CBG (mg/dl) 173 ± 43 187 ± 62 218 ± 46 % pt days with ≥ 1 CBG < 70 All CBG 70-180 ≥ 1 CBG 181-300 ≥ 1 CBG > 300 % pt days with ≥ 1 CBG < 70 All CBG 70-180 ≥ 1 CBG 181-300 ≥ 1 CBG > 300 21 25 56 22 21 25 56 22 10 24 55 7 10 24 55 7 20 24 73 60 20 24 73 60 IDS = inpatient diabetes service IPP = inpatient pump protocol

31. Inpatient Insulin Therapy in Patients Treated with Insulin as Outpatients Patients completing questionnaire (n = 17) reported a high degree of satisfaction with their ability to continue CSII therapy in the hospital There were 2 CSII related adverse events –1 infusion site problem –1 pump malfunction Patients completing questionnaire (n = 17) reported a high degree of satisfaction with their ability to continue CSII therapy in the hospital There were 2 CSII related adverse events –1 infusion site problem –1 pump malfunction Noschese ML et al Endocrine Practice 15:415 2009

32. Inpatient CSII Therapy Bailon RM et al Endocrine Practice 15:25 2009 Prevalence of hyperglycemia and hypoglycemia in inpatients who continued (Pump on) or discontinued (Pump off) CSII during their hospital stay Prevalence of hyperglycemia and hypoglycemia in inpatients who continued (Pump on) or discontinued (Pump off) CSII during their hospital stay

33. Hyperglycemic Events in Patients Continuing or Stopping CSII Therapy During their Hospital Stay Bailon RM et al Endocrine Practice 15:25 2009 Blood glucose mg/dl Pump On Pump Off Values per person

34. Hypoglycemic Events in Patients Continuing or Stopping CSII Therapy During their Hospital Stay Bailon RM et al Endocrine Practice 15:25 2009 Blood glucose mg/dl Pump On Pump Off

35. Implications of this study There was less hypoglycemia among patients who continued to use their insulin pump during their hospital stay Bailon RM et al Endocrine Practice 15:25 2009

36. Clinical Situations Associated with Inpatient Hyperglycemia Enteral or parenteral nutrition Glucocorticoid therapy Enteral or parenteral nutrition Glucocorticoid therapy

37. Complications of Enteral Nutrition A prospective and observational study carried out in 64 patients average age (mean age 76.2 y) receiving EN on an Internal Medicine Inpatient Unit with Most frequent complications: Tube dislodgement (48.5%) Electrolytic alterations (45.5%) Hyperglycemia (34.5%) Diarrhea (32.8%) Constipation (29.7%) Vomiting (20.4%) Clogging of tube (12.5%) Aspiration (3.1%) A prospective and observational study carried out in 64 patients average age (mean age 76.2 y) receiving EN on an Internal Medicine Inpatient Unit with Most frequent complications: Tube dislodgement (48.5%) Electrolytic alterations (45.5%) Hyperglycemia (34.5%) Diarrhea (32.8%) Constipation (29.7%) Vomiting (20.4%) Clogging of tube (12.5%) Aspiration (3.1%) Pancorbo Hidalgo PL J Clin Nsg 10:482 2001

38. Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009

39. Treatment Algorithm For Patients Receiving Continuous Enteral Nutrition ≥ 2 BG > 130 mg/dl Continue current regimen ≥ 2 BG >180 mg/dl in prior 24 hours Add 25-50% Correction Insulin to Glargine Administer regular insulin q6h ≥ 2 BG >180 mg/dl in prior 24 hours Add 25-50% Correction Insulin to Glargine Administer regular insulin q6h Glargine 10 units + Correction Insulin q6h Patient with no prior history diabetes started on EN All BG < 130 mg/dl Discontinue BG Monitoring BG < 130 mg/dl x 48 hrs

40. Alternative Treatment Algorithm For Patients Receiving Continuous Enteral Nutrition ≥ 2 BG > 130 mg/dl Continue regimen ≥ 2 BG >180 mg/dl in prior 24 hours ≥ 1 BG > 250 mg/dl in prior 24 hours ≥ 2 BG >180 mg/dl in prior 24 hours ≥ 1 BG > 250 mg/dl in prior 24 hours Initiate correction insulin q6h All BG < 180 mg/dl Discontinue BG Monitoring BG < 130 mg/dl x 48 hrs Patient with no prior history diabetes started on EN Start Scheduled Insulin Therapy

41. GlargineCI*P value Mean CBG during study mg/dl163±31161±30.75 Hypoglycemia/pt days %2.74.8.34 Hyperglycemia/pt days %49.347.6.77 Blood Glucose Data on Participants According to Group Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009 There were no group differences in adverse events. *CI= correction insulin

42. Summary 50% of eligible subjects for this study had no previous history of type 2 diabetes or hyperglycemia Both glargine and correction insulin (CI) (with the addition of NPH) were effective at achieving glycemic control in these patients with careful glucose monitoring and adjustments of the insulin regimen 13/25 patients randomized to correction insulin alone required NPH insulin to achieve glycemic control No severe hypoglycemia events occurred during this study 50% of eligible subjects for this study had no previous history of type 2 diabetes or hyperglycemia Both glargine and correction insulin (CI) (with the addition of NPH) were effective at achieving glycemic control in these patients with careful glucose monitoring and adjustments of the insulin regimen 13/25 patients randomized to correction insulin alone required NPH insulin to achieve glycemic control No severe hypoglycemia events occurred during this study Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009

43. Implications of this study Bedside glucose monitoring is recommended for all hospitalized patients with and without a prior history of diabetes with initiation or augmentation of enteral nutrition. Glargine insulin is effective at achieving and maintaining glycemic control in patients receiving both continuous and intermittent enteral nutrition without increasing the risk for hypoglycemia. Bedside glucose monitoring is recommended for all hospitalized patients with and without a prior history of diabetes with initiation or augmentation of enteral nutrition. Glargine insulin is effective at achieving and maintaining glycemic control in patients receiving both continuous and intermittent enteral nutrition without increasing the risk for hypoglycemia. Korytkowski M, Salata R, Koerbel G et al Diabetes Care 32:594, 2009

44. Glycemic Management of the Patient Receiving Enteral Nutrition Continuous enteral nutrition (EN) Basal: 40-50% of TDD as long or intermediate acting insulin given once twice a day Short acting 50-60% of TDD given q6h Cycled enteral nutrition Intermediate acting insulin given together with a rapid or short acting insulin with start of TF Rapid or short acting insulin administered q4 to 6 hours for duration of EN administration Correctional insulin given for BG above goal range Bolus enteral nutrition Rapid acting analog or short acting insulin given prior to each bolus Continuous enteral nutrition (EN) Basal: 40-50% of TDD as long or intermediate acting insulin given once twice a day Short acting 50-60% of TDD given q6h Cycled enteral nutrition Intermediate acting insulin given together with a rapid or short acting insulin with start of TF Rapid or short acting insulin administered q4 to 6 hours for duration of EN administration Correctional insulin given for BG above goal range Bolus enteral nutrition Rapid acting analog or short acting insulin given prior to each bolus

45. Glycemic Management of the Patient Receiving Enteral Nutrition Suggested Dose of short acting insulin can be based on anticipated “dose” of carbohydrate Example: 67 yo woman receiving Peptamin with calculated 188 G of carbohydrate over 24 hrs Insulin to carbohydrate ratio: 1 unit/10 G Calculated total insulin dose 19 units Administered total insulin dose over 24 h 20 units BG over 1 st 36 hours 90-135 mg/dl Suggested Dose of short acting insulin can be based on anticipated “dose” of carbohydrate Example: 67 yo woman receiving Peptamin with calculated 188 G of carbohydrate over 24 hrs Insulin to carbohydrate ratio: 1 unit/10 G Calculated total insulin dose 19 units Administered total insulin dose over 24 h 20 units BG over 1 st 36 hours 90-135 mg/dl

46. Recommendations for Patients Receiving Parenteral and Enteral Nutrition Initiate bedside capillary blood glucose (CBG) monitoring for all patients receiving enteral nutrition (EN). Continue glucose monitoring during upward (or downward) titrations of enteral nutrition Initiate correctional insulin for any patient with CBG levels > 140 mg/dL during EN. Consider use diabetes-specific formulas in patients with pre-existing diabetes. Consider use of Diabetes-specific formulas in patients with new onset or difficult to control hyperglycemia. Initiate bedside capillary blood glucose (CBG) monitoring for all patients receiving enteral nutrition (EN). Continue glucose monitoring during upward (or downward) titrations of enteral nutrition Initiate correctional insulin for any patient with CBG levels > 140 mg/dL during EN. Consider use diabetes-specific formulas in patients with pre-existing diabetes. Consider use of Diabetes-specific formulas in patients with new onset or difficult to control hyperglycemia.

47. Glycemic Management of the Patient Receiving Enteral Nutrition Patients who already have an underlying diagnosis of diabetes are likely to experience further elevations in blood glucose levels with the initiation of enteral nutrition 1. Patients receiving EN often have a higher severity of illness that those who do not. Unanticipated dislodgement of a feeding tube, temporary discontinuation of the feedings, or changes in the rate of administration can result in hypoglycemia. Protocols for avoidance and early treatment of hypoglycemia are recommended in case of abrupt discontinuation of EN. For example: Keep order in place to start dextrose-containing IVFs in event of abrupt discontinuation of EN Patients who already have an underlying diagnosis of diabetes are likely to experience further elevations in blood glucose levels with the initiation of enteral nutrition 1. Patients receiving EN often have a higher severity of illness that those who do not. Unanticipated dislodgement of a feeding tube, temporary discontinuation of the feedings, or changes in the rate of administration can result in hypoglycemia. Protocols for avoidance and early treatment of hypoglycemia are recommended in case of abrupt discontinuation of EN. For example: Keep order in place to start dextrose-containing IVFs in event of abrupt discontinuation of EN

48. Enteral Nutritional Support and Use of Diabetes Specific Formulas Standard formulas High in carbohydrate Low Fat Low fiber Standard formulas High in carbohydrate Low Fat Low fiber Diabetes Specific Formulas 35–40% of calories from carbohydrate 15% of calories from fructose 40-50% of calories from fat with a large contribution from MUFAs (e.g. >60% of fat calories) Diabetes Specific Formulas 35–40% of calories from carbohydrate 15% of calories from fructose 40-50% of calories from fat with a large contribution from MUFAs (e.g. >60% of fat calories) Marinos et al. Diabetes Care 28:2267 2005

49. Postprandial Rise in Blood Glucose and Type of EN Formula Marinos et al Diabetes Care 28:2267 2005 N = 20 Hi MUFA fructose fibre Peters 1989 N = 40 Hi MUFA fructose fibre Stanz Paris 1998 N = 12 Hi MUFA fructose fibre Stanz Paris 1998 N = 61 Hi MUFA fructose fibre Mesejo 2003 Meta analysis Long term N = 34 Hi MUFA fructose fibre Craig 1998 N = 11 Hi MUFA fructose fibre del Carmen Crespillo 2003 Meta analysis Short term Meta analysis All studies Favors specific Favors Standard -6 -4 -2 0 2 4 6 Postprandial rise in BG reduced by 18 mg/dl (1.03 mmol)

50. Peak Blood Glucose and Type of EN Formula Marinos et al Diabetes Care 28:2267 2005 N = 24 Hi MUFA fructose fibre Hofman 2004 Meta analysis Favors specific Favors Standard -3 -2 -1 0 1 2 3 N = 20 Hi MUFA fructose fibre Hofman 2004 Postprandial rise in BG reduced by 29 mg/dl (1.59 mmol)

51. Glycemic Management of the Patient Receiving TPN Usual method Adding incremental doses of insulin to TPN based on previous days requirement of correctional (sliding scale insulin) Other (preferred?) Use of a separate IV insulin infusion titrated according to bedside glucose levels There are no controlled trials examining different strategies for achieving glycemic control in this group of patients Usual method Adding incremental doses of insulin to TPN based on previous days requirement of correctional (sliding scale insulin) Other (preferred?) Use of a separate IV insulin infusion titrated according to bedside glucose levels There are no controlled trials examining different strategies for achieving glycemic control in this group of patients

52. Glycemic Management of the Patient Receiving TPN Suggested In patients with known type 2 diabetes, add 1 unit for each 10 Grams of carbohydrate in the solution Initiate Correctional Insulin Scale for BG > 140 mg/dl Add 60 to 100% of previous days correctional insulin dose to next day’s TPN solution Consider Add basal long or intermediate acting insulin at a dose of 0.2 to 0.4 units per kg per day Suggested In patients with known type 2 diabetes, add 1 unit for each 10 Grams of carbohydrate in the solution Initiate Correctional Insulin Scale for BG > 140 mg/dl Add 60 to 100% of previous days correctional insulin dose to next day’s TPN solution Consider Add basal long or intermediate acting insulin at a dose of 0.2 to 0.4 units per kg per day

53. Frequency of hyperglycemia in patients receiving high dose steroids % % Donihi A et al Endocrine Practice 12:358, 296 > 1 BG > 200 mg/dl> 2 BG > 200 mg/dl 64 56 81 52 41 75 0 0 30 60 90 All No Hx DM Hx DM

54. Steroid Therapy and Inpatient Glycemic Control The majority of patients receiving > 2 days of glucocorticoid therapy at a dose equivalent of at least 40 mg per day of Prednisone developed hyperglycemia No glucose monitoring was performed in 24% of patients receiving high dose glucocorticoid therapy The majority of patients receiving > 2 days of glucocorticoid therapy at a dose equivalent of at least 40 mg per day of Prednisone developed hyperglycemia No glucose monitoring was performed in 24% of patients receiving high dose glucocorticoid therapy Donihi A et al Endocrine Practice 12:358, 296

55. Risk for New Onset Diabetes with Glucocorticoid Therapy Clore JN, Thurber-Hay L. Endocrine Practice 15:469 2009

56. One Suggested Approach for Treatment of Hyperglycemia in Patients Receiving Glucocorticoid Therapy Clore JN, Thurber-Hay L. Endocrine Practice 15:469 2009 Prednisone (mg/day)NPH (units/kg/day)* > 400.4 300.3 200.2 100.1 *Administered in AM at time of prednisone administration Glargine preferred if dexamethasone used or Prednisone given twice a day *Administered in AM at time of prednisone administration Glargine preferred if dexamethasone used or Prednisone given twice a day

57. How do Steroids Differ in their Effects? Steroid Potency and Duration of Action 20mg/d of prednisone ~= 80mg/d of hydrocortisone ~= 16mg/d of methylprednisolone ~= 3mg/d dexamethasone) Glucocorticoid PotencyBiologic Half Life Hydrocortisone18-12 hours Prednisone418-36 hours Methylprednisolone518-36 hours Dexamethasone30-4036-54 hours

58. Steroid Therapy and Glycemic Control General Guidelines The majority of patients (but not all) receiving high dose glucocorticoid therapy will experience elevations in blood glucose For patients without prior DM or hyperglycemia or those with diabetes controlled with oral agents: Initiate glucose monitoring with low dose correction insulin scale administered prior to meals For patients previously treated with insulin Increase total daily dose by 20 to 40% with start of high dose steroid therapy Increase correctional insulin by one step (low to moderate dose) Adjust insulin as needed to maintain glycemic control The majority of patients (but not all) receiving high dose glucocorticoid therapy will experience elevations in blood glucose For patients without prior DM or hyperglycemia or those with diabetes controlled with oral agents: Initiate glucose monitoring with low dose correction insulin scale administered prior to meals For patients previously treated with insulin Increase total daily dose by 20 to 40% with start of high dose steroid therapy Increase correctional insulin by one step (low to moderate dose) Adjust insulin as needed to maintain glycemic control

59. IV Insulin Infusions may be required to maintain glycemic control in some patients Steroid Therapy and Glycemic Control General Guidelines

60. Glucocorticoid Therapy Suggested approach : Institute glucose monitoring for at least 48 hours in all patients Prescribe insulin therapy as needed according to results of bedside BG monitoring During initiation and taper of steroid therapy, proactive adjustment of insulin therapy can help avoid uncontrolled hyperglycemia and hypoglycemia. Suggested approach : Institute glucose monitoring for at least 48 hours in all patients Prescribe insulin therapy as needed according to results of bedside BG monitoring During initiation and taper of steroid therapy, proactive adjustment of insulin therapy can help avoid uncontrolled hyperglycemia and hypoglycemia.

61. Bromage et al. Surg Gynecol Obstet June 1971 Changes in Blood Glucose During Surgery in Patients without Diabetes General Anesthesia Epidural Anesthesia % Change in blood glucose 70%

62. Pre-Op Recommendations for Patients Admitted Day of Surgery Oral Hypoglycemic Agents Withhold oral agents the morning of surgery Insulin is necessary to control blood glucose in patients with BG > 150 during surgery Oral agents can be resumed postoperatively when Patient is reliably taking PO Risk of liver, kidney and heart failure are minimized Withhold oral agents the morning of surgery Insulin is necessary to control blood glucose in patients with BG > 150 during surgery Oral agents can be resumed postoperatively when Patient is reliably taking PO Risk of liver, kidney and heart failure are minimized

63. Give at least 50 to 70 % of usual dose of NPH insulin and 70 to 100 % of detemir or glargine insulin For patients receiving premix insulin (70/30 or 75/25), give 1/3 of total dose as NPH insulin prior to the procedure For patients undergoing prolonged procedures (e.g. CABG) hold SQ insulin and start IV insulin infusion Give at least 50 to 70 % of usual dose of NPH insulin and 70 to 100 % of detemir or glargine insulin For patients receiving premix insulin (70/30 or 75/25), give 1/3 of total dose as NPH insulin prior to the procedure For patients undergoing prolonged procedures (e.g. CABG) hold SQ insulin and start IV insulin infusion Pre-op Recommendations for Patients Admitted Day of Surgery Insulin Treated Patients

64. Mucha et al. Diabetes Care 27:1209 2004 Study of Glargine Insulin During Fasting in Subjects with Type 1 Diabetes Plasma glucose mg/dl Fasting Control Usual dose of glargine insulin administered while fasting or on another day in combination with usual prandial insulin (Control) N = 15 This study suggests the safety of administering a percentage of basal insulin when a patient is made NPO.

65. DC insulin pump and change to IV insulin according to patients current basal rate If basal rate < 1 unit/h, start IV insulin at 0.5 units/h h If basal rate 1-2 units/h, start IV insulin at 1 units/h Preoperative Recommendations Patients using insulin pump therapy Hypoglycemia and hyperglycemia are treated in manner similar to that of patients receiving SQ insulin pre-op

66. General Guidelines Inpatient use of U500 insulin is reserved for patients who use this concentrated form of regular insulin as outpatients and who demonstrate a similar or greater degree of insulin resistance at time of hospital admission. To avoid dosing errors that have potential for hypoglycemia, many hospitals regulate the administration of U500 insulin by requiring one or all of the following: Order written as volume to be given using a TB syringe All doses prepared in pharmacy Alerts in patient room and on patient medicine administration record General Guidelines Inpatient use of U500 insulin is reserved for patients who use this concentrated form of regular insulin as outpatients and who demonstrate a similar or greater degree of insulin resistance at time of hospital admission. To avoid dosing errors that have potential for hypoglycemia, many hospitals regulate the administration of U500 insulin by requiring one or all of the following: Order written as volume to be given using a TB syringe All doses prepared in pharmacy Alerts in patient room and on patient medicine administration record Can U500 Regular Insulin Be Used in the Hospital?

67. Management of Hyperglycemia in the Hospital and Patient Safety Concern Both under and over-treatment of hyperglycemia create safety concerns in hospitalized patients. Areas of risk: Changes in carbohydrate or food intake Changes in clinical status or medications Failure to adjust therapy based on BG patterns Prolonged use of SSI as monotherapy Poor coordination of BG testing with insulin administration and meal delivery Poor communication during patient transfers Errors in order writing and transcription Both under and over-treatment of hyperglycemia create safety concerns in hospitalized patients. Areas of risk: Changes in carbohydrate or food intake Changes in clinical status or medications Failure to adjust therapy based on BG patterns Prolonged use of SSI as monotherapy Poor coordination of BG testing with insulin administration and meal delivery Poor communication during patient transfers Errors in order writing and transcription

68. Summary BG levels of 100-180 mg/dl are suggested for the majority of non-critically ill patients Insulin therapy the preferred method for achieving and maintaining glycemic control in the hospital Scheduled SQ Basal Bolus insulin therapy is effective and safe for treatment of hyperglycemia in non-critically ill patients Correction insulin alone may be appropriate for periods of < 24 to 48 hours in patients without a prior history of diabetes or prior insulin therapy with initiation of therapies known to be associated with high risk for hyperglycemia (TPN, EN, Steroids) Prolonged monotherapy with correction insulin is inappropriate once an insulin requirement is established with correction insulin Proactive adjustments in the hypoglycemic regimen are required for both initiation and tapering of steroid therapy BG levels of 100-180 mg/dl are suggested for the majority of non-critically ill patients Insulin therapy the preferred method for achieving and maintaining glycemic control in the hospital Scheduled SQ Basal Bolus insulin therapy is effective and safe for treatment of hyperglycemia in non-critically ill patients Correction insulin alone may be appropriate for periods of < 24 to 48 hours in patients without a prior history of diabetes or prior insulin therapy with initiation of therapies known to be associated with high risk for hyperglycemia (TPN, EN, Steroids) Prolonged monotherapy with correction insulin is inappropriate once an insulin requirement is established with correction insulin Proactive adjustments in the hypoglycemic regimen are required for both initiation and tapering of steroid therapy