Diabetes Management in the Hospital

3. Diabetes in Hospitalized Patients1997

4. Diabetes in Hospitalized Patients1997 Costs

5. Diabetes in Hospitalized PatientsReason for Higher Costs Higher Rate of Hospitalization Longer Stays More Procedures, Medications Chronic Complications More Arteriosclerotic Disease More Infections Complicated Pregnancies

7. Infections in Diabetes More Frequent Bacteremia Septic Shock Pyelonephritis Candida TPN Unique Necrotizing Fasciitis Fournier’s Gangrene Mucoromycosis Emphysematous GB Malignant External Otitis

8. Infections in Diabetes One BG >220 mg/dl results in 5.8 times increase in nosocomial infection rate Two hours hyperglycemia results in impaired WBC function for weeks

9. TPN In DiabetesVA Cooperative Trial Benefit Negated Increased Infections Related to Hyperglycemia

10. Side Effects of BG >200 mg/dl Reduced Intravascular Volume Dehydration Electrolyte Fluxes Impaired WBC Function Immunoglobulin Inactivation Complement Disabling Increased Collagenase, Decreased Wound Collagen

11. Psychology of Diabetes in Hospital Patients expect good glycemic control as part of hospital care They strive for recommended goals at home Difficult to understand staff’s casual approach to BG’s >150

12. Evidence for Immediate Benefit of Normoglycemia in Hospitalized Patients Numerous Publications on in Vitro Evidence Neutrophil Dysfunction Complement Inhibition Altered Redox State (Pseudohypoxia) Glucose Rich Edema as Culture Media Six Recent Clinical Publications supporting good glucose control in the hospital setting

13. Open Heart Surgery in DiabetesPortland St. Vincent Medical Center Control Group N=968 1987-1991 SubQ Insulin q 4 h Goal 200 mg/dl Standard Deviation 36 All Mean BG’s <200 47% Study Group N=1499 1991-1997 IV Insulin Goal 150-200 mg/dl Standard Deviation 26 All Mean BG’s <200 84%

14. Open Heart Surgery in DiabetesPortland CII ProtocolDemographics Total Open Heart Surgery Patients 14,468 Diabetes at Admission 2467 (17%) Age 65 SD 10 Males 62% Insulin Rx 36% OHA 48%

15. Open Heart Surgery in DiabetesPortland St. Vincent Medical Center Perioperative Blood Glucose

16. Incidence of DSWI: 1987-1997

17. Open Heart Surgery in DiabetesPortland CII ProtocolInfectious Complications Diabetes 31/2467 (1.3%) Deep Sternal Wound Infection (DSWI) 23/31 Required Second Admission 22 Micrococcus 0 Anaerobes, fungal, yeast Non-Diabetes 40/12,005 (0.3%)

18. Open Heart Surgery in DiabetesPortland CII ProtocolMortality All (99/2467) 4.0% SQI 6.1% CII 3.0% DSWI 19.0% No DSWI 3.8% Recent Experience 1994-1997 DSWI as in non-diabetics 1996-7 No DSWI in last 15 mo.

19. Open Heart Surgery in DiabetesPortland CII ProtocolComparison of GroupsHigher Risk Patients in CII Group

20. Open Heart Surgery in DiabetesPortland CII ProtocolUnivariate Analysis of DSWI

22. Open Heart Surgery in DiabetesPortland CII ProtocolWeakness of Study Not Randomized Temporal Sequential Nature Subtle Cumulative Improvements in Techniques

23. Open Heart Surgery in DiabetesPortland CII ProtocolConclusions Magnitude and Strength of Study is Compelling Ethics of Confirming Study Would be Questionable Application of CII is Simple and Safe Hyperglycemia Predicts DSWI CII Prevents DSWI

24. Open Heart Surgery in DiabetesJohn Hopkins Prospective Cohort Study of 411 OHS pts with Diabetes 1990 – 1995 Diabetes based on history (42% insulin treated, 45% oral agents) SMBG 4x/day with sliding scale Measured relationship between peri-operative control and risk of all infections

25. Open Heart Surgery in DiabetesJohn Hopkins 24.3% with infections BG divided into quartiles Relative Odds Q1 121-206 20.1% Q2 207-229 21.6% 1.17 Q3 230-252 29.8% 1.86* Q4 252-352 25.7% 1.72*

26. DIGAMI StudyDiabetes, Insulin Glucose Infusion in Acute Myocardial Infarction(1997) Acute MI With BG > 200 mg/dl Intensive Insulin Treatment IV Insulin For > 24 Hours Four Insulin Injections/Day For > 3 Months Reduced Risk of Mortality By: 28% Over 3.4 Years 51% in Those Not Previous Diagnosed

27. Cardiovascular RiskMortality After MI Reduced by Insulin Therapy in the DIGAMI Study Slide 6-11 BARRIERS TO INSULIN THERAPY Cardiovascular Risk Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study Patients at high risk of cardiovascular disease are often thought to be inappropriate candidates for treatment with insulin because of the belief that hypoglycemia, hyperinsulinemia, or other metabolic effects of insulin might provoke or worsen the outcome of major cardiovascular events. This figure shows data from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial. This Swedish trial studied the short-term and long-term effects of intensive insulin treatment of patients with diabetes who were enrolled in the trial at the time of a myocardial infarction. The subjects were immediately randomized to continued management according to the judgment of their physicians, or to intravenous infusion of insulin and glucose for 48 hours followed by a four-injection regimen subsequently for as long as 5 years. Other aspects of management of the infarction included treatment with b-blockers, angiotensin-converting enzyme inhibitors, fibrinolytic agents, and aspirin in high proportions of both groups. The rationale underlying the study was the old observation that, in animal experiments and studies of small numbers of humans, infarct size and outcome are improved by insulin-glucose infusion, in part because of suppression of otherwise elevated free fatty acid levels in plasma. The figure shows the cumulative total mortality rates in the whole population of 620 subjects randomized to the two treatments, as well as the rates for a predefined subgroup of subjects who were judged likely to survive the initial hospitalization and were not previously using insulin. The whole population showed an 11% actual and a 28% relative risk reduction with intensive insulin treatment after 5 years, and the subgroup showed a 15% actual and a 51% relative risk reduction. Most of the benefit was apparent in the first month of treatment and presumably was partly due to immediate intravenous infusion of insulin; however, the survival curves tended to separate further over time, suggesting an ongoing benefit from intensive treatment. This study suggests that insulin is an entirely appropriate treatment for patients with type 2 diabetes and high cardiovascular risk, especially at the time of myocardial infarction. Malmberg K, Rydén L, Hamsten A, Herlitz J, Waldenström, Wedel H, and the DIGAMI study group. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. Eur Heart J. 1996;17:1337-1344; Nattrass M. Managing diabetes after myocardial infarction: time for a more aggressive approach. BMJ. 1997;314:1497; Malmberg K, and the DIGAMI study group. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997;314:1512-1515.Slide 6-11 BARRIERS TO INSULIN THERAPY Cardiovascular Risk Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study Patients at high risk of cardiovascular disease are often thought to be inappropriate candidates for treatment with insulin because of the belief that hypoglycemia, hyperinsulinemia, or other metabolic effects of insulin might provoke or worsen the outcome of major cardiovascular events. This figure shows data from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial. This Swedish trial studied the short-term and long-term effects of intensive insulin treatment of patients with diabetes who were enrolled in the trial at the time of a myocardial infarction. The subjects were immediately randomized to continued management according to the judgment of their physicians, or to intravenous infusion of insulin and glucose for 48 hours followed by a four-injection regimen subsequently for as long as 5 years. Other aspects of management of the infarction included treatment with b-blockers, angiotensin-converting enzyme inhibitors, fibrinolytic agents, and aspirin in high proportions of both groups. The rationale underlying the study was the old observation that, in animal experiments and studies of small numbers of humans, infarct size and outcome are improved by insulin-glucose infusion, in part because of suppression of otherwise elevated free fatty acid levels in plasma. The figure shows the cumulative total mortality rates in the whole population of 620 subjects randomized to the two treatments, as well as the rates for a predefined subgroup of subjects who were judged likely to survive the initial hospitalization and were not previously using insulin. The whole population showed an 11% actual and a 28% relative risk reduction with intensive insulin treatment after 5 years, and the subgroup showed a 15% actual and a 51% relative risk reduction. Most of the benefit was apparent in the first month of treatment and presumably was partly due to immediate intravenous infusion of insulin; however, the survival curves tended to separate further over time, suggesting an ongoing benefit from intensive treatment. This study suggests that insulin is an entirely appropriate treatment for patients with type 2 diabetes and high cardiovascular risk, especially at the time of myocardial infarction. Malmberg K, Rydén L, Hamsten A, Herlitz J, Waldenström, Wedel H, and the DIGAMI study group. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. Eur Heart J. 1996;17:1337-1344; Nattrass M. Managing diabetes after myocardial infarction: time for a more aggressive approach. BMJ. 1997;314:1497; Malmberg K, and the DIGAMI study group. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997;314:1512-1515.

28. ICU Survival 1548 Patients (mostly OHS pts.) All with BG >200 mg/dl Randomized into two groups Maintained on IV insulin Conventional group (BG 180-200) Intensive group (BG 80-110) Conventional Group had 1.74 X mortality

29. ICU IV Insulin Protocol If > 100 mg/dl, 2 U/h If > 200 mg/dl, 4 U/h If > 140 mg/dl, increase by 1 – 2 U/h If 121 to 140 mg/dl, increase by 0.5 – 1 U/h If 111 to 120 mg/dl, increase by 0.1 – 0.5 U/h If 81 to 110 mg/dl, no change If 61 to 80 mg/dl, change back to prior rate

30. ICU Survival Blood glucose control: Convetional Intensive Mean AM BG 153 103 % Receiving Insulin 39% 100% BG < 40 mg/dl 6 39

31. ICU Survival Intensive Therapy (80 to 110 mg/dL) resulted in: 34% reduction in mortality 46% reduction in sepsis 41% reduction in dialysis 50% reduction in blood transfusion 44% reduction in polyneuropathy

32. Conclusion All hospital patients should have normal glucose

33. Insulin The agent we haveto control glucose

34. Comparison of Human Insulins / Analogues Insulin Onset of Duration ofpreparations action Peak action

35. Physiological Serum Insulin Secretion Profile

36. Basal/Bolus Treatment Program withRapid-acting and Long-acting Analogs

37. Methods For Managing Hospitalized Persons with Diabetes Continuous Variable Rate IV Insulin Drip Major Surgery, NPO, Unstable, MI, DKA, Hyperglycemia, Steroids, Gastroparesis, Delivery, etc Basal / Bolus Therapy (MDI) when eating

38. Continuous Variable Rate IV Insulin Drip Mix Drip with 125 units Regular Insulin into 250 cc NS Starting Rate Units / hour = (BG – 60) x 0.02 where BG is current Blood Glucose and 0.02 is the multiplier Check glucose every hour and adjust drip Adjust Multiplier to keep in desired glucose target range (100 to 140 mg/dl)

39. Continuous Variable Rate IV Insulin Drip Adjust Multiplier (initially 0.02) to obtain glucose in target range 100 to 140 mg/dL If BG > 140 mg/dL, increase by 0.01 If BG < 100 mg/dL, decrease by 0.01 If BG 100 to 140 mg/dL, no change in Multiplier If BG is < 80 mg/dL, Give D50 cc = (100 – BG) x 0.3 Give continuous rate of Glucose in IVF’s Once eating, continue drip till 1 hour post SQ insulin

40. Glucose Management System

41. Glucommander Based on 15 Year Experience with a Computer Based Algorithm for the Administration of IV Insulin Developed for Marketing by MiniMed and Roche GMS System Shelved Pending FDA Approval of IV Use of Insulin Useful and Safe for Any Application of IV Insulin

43. Glucommander Effectiveness Initial blood glucose Median 292 mg/dl Range 181-1,568 Time to achieve glucose < 180 mg/dl Median 3 hours Range 0.3 - 19.7 Time to achieve three consecutive glucose results between 60 - 180 mg/dL Median 3. 1 hours Range 0.3 - 22.5

44. Converting to SQ insulin Establish Daily Insulin Requirement IV Insulin First Night (BG - 60) x Multiplier = Ins/hr Targeted to 120 60 x Multiplier x 24 = Daily Insulin Requirement Give One-Half Amount As Basal Give p.c. Boluses Based on CHO Intake Start at CHO/Ins 1 CHO = 1.5 units Rapid-acting Monitor a.c. tid, hs, and 3 am Supplement All BG >150 (BG-100)/(1700/Daily Insulin Requirement)

45. Protocol for SQ Insulin in Hospitalized Patient Bedtime: Wt (kg) x 0.2 = Units of Glargine Meals Eaten: 1.5 units per 15 Gm CHO eaten BG >150: (BG-100) / CF CF = 3000 / Wt (kg) Do Not Use Sliding Scale Only Any BG <80: D50 = (100-BG) x 0.3 ml Maintain INT Do Not Hold Insulin When BG Normal

46. How to Initiate MDI Starting dose = 0.4 to 0.5 x weight in kilograms Bolus dose (aspart/lispro) = 20% of starting dose at each meal Basal dose (glargine) = 40% of starting dose given at bedtime or anytime Correction bolus = (BG - 100)/ Correction Factor, where CF = 1700/total daily dose

47. How to Initiate MDI starting dose = 0.45 x wgt. in kg Wt. is 80 kg; 0.45 x 80 = 36 units Bolus dose (aspart / lispro) = 20% of starting dose at each meal; 0.2 x 36 = 7 units ac (tid) Basal dose (glargine) = 40% of starting dose at HS; 0.4 x 36 = 14 units at HS Correction bolus = (BG - 100)/ CF, where CF = 1700/total daily dose; CF = 50

48. Correction Bolus Formula Example: Current BG: 250 mg/dl Ideal BG: 100 mg/dl Glucose Correction Factor: 50 mg/dl

49. Piedmont Diabetes PlanWhat Can We Do For Patients Admitted To Hospital? NPO Pathway For All Diabetes Patients Finger Stick BG ac qid on ALL Admissions Check All Steroid Treated Patients Diagnose Diabetes FBG >126 mg/dl Any BG >200 mg/dl

50. Piedmont Diabetes PlanWhat Can We Do For Patients Admitted To Hospital?  Document Diagnosis in Chart Hyperglycemia Is Diabetes Until Proven Bring to All Physician’s Attention Note on Problem List and Face Sheet Check Hemoglobin A1C Hold Metformin; Hold TZD with CHF, Liver Dysfunction Start Insulin in All Hospitalized Patients Not Already on Insulin

51. Piedmont Diabetes PlanWhat Can We Do For Patients Admitted To Hospital?  Get Diabetes Education Consult Instruct Patient in Monitoring and Recording See That Patient Has Meter on Discharge Decide on Case Specific Program for Discharge Arrange Early F/U with PCP

52. Piedmont Diabetes PlanWhat Can We Do For Patients Admitted To Hospital?  Follow Guidelines For Endocrinology Consult Any Hypoglycemia Requiring Intervention DKA or HHNC Patient on Insulin Pump Diabetes in Pregnancy Glucocorticoid Therapy in Diabetes Progressive Diabetes Complications A1C >8%, Microalbuminuria >30 mg

53. Treat Any Patient With BG > 150 With Insulin Treat Any BG >150 with Rapid-acting Insulin (BG-100) / (5000 / wt #) or (3000 / wt kg) Treat Any Recurrent BG >200 with IV Insulin If More than 0.5 u/hr IV Insulin Required with Normal BG Start Long Acting Insulin Protocol for Insulin in Hospitalized Patient

54. Protocol for Insulin in Hospitalized Patient Daily Total: Pre-Admission or Weight (#) x 0.2 u 40 % as Glargine (Basal) 60% as Rapid-acting insulin (Bolus) Give in Proportion to Meal’s CHO Eaten BG >150: (BG-100) / CF CF = 5000 / Wt(#) or 3000 / Wt(kg) Do Not Use Sliding Scale As Only Diabetes Management

55. Protocol for Insulin in Hospitalized Patient Treatment of Hypoglycemia Any BG <80 mg/dl: D50 = (100-BG) x 0.3 ml IV Do Not Hold Insulin When BG Normal

56. Diabetes at Piedmont HospitalConclusions Any BG >200 mg/dl Is Diabetes (Fasting >126 mg/dl) Most Diabetes Is Type 2 All DM patients Must Self-Monitor BG’s and Record No BG >150 mg/dl Should Go Untreated Most Hospitalized DM [atients Should Be on Insulin IV Insulin is Most Effective, Efficient, Safest Rx in Acute Illness (Glucommander)

57. Diabetes at Piedmont HospitalConclusions 2 Type 2 Diabetics Are Resistant to Insulin Reactions Treat Insulin Reactions in Hospital With IV Glucose Do Not Be Hold Insulin for Normal BG, i.e. 80-120 mg/dl A1C Values >7% Indicates Sub-optimal Care

58. Diabetes at Piedmont HospitalConclusions 3 Discharge Plan For BG Control You Are the Link Between the Best Diabetes Care and the Patient Use Your Diabetes Resources Diabetes Education Center Endocrinologists

59. The Paradigm for the MilleniumHyperglycemia: A Mortal Sin A blood glucose over 200 in a hospitalized patient causes increased morbidity and mortality. In the 21st Century Neglecting a BG >200 Will Be Malpractice

60. Conclusion Intensive therapy is the best way to treat patients with diabetes

61. QUESTIONS For a copy or viewing of these slides, contact WWW.adaendo.com