I need help

1. I need help! Searching for Diabetes Type 2 patients Drug Na�ve New category of oral agent Clinical outpatient trial Email me: oatess@arnett.com Call me 448-8007

3. Today Money Mortality Morbidity Math (I love algebra)

4. Diabetes in Hospitalized Patients1997

5. Diabetes in Hospitalized Patients1997 Costs

6. 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

8. Infections in Diabetes More Frequent Bacteremia Septic Shock Pyelonephritis Candida Unique Necrotizing Fasciitis Fournier�s Gangrene Mucormycosis Malignant External Otitis

10. 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

11. 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

12. 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 >200

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

14. 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%

15. 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% Oral diabetes agent 48%

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

17. Incidence of DSWI: 1987-1997

18. 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%)

19. 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.

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

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

22. Interesting exercise in calculating savingsInteresting exercise in calculating savings

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

24. Open Heart Surgery in DiabetesPortland CII ProtocolConclusions Magnitude and Strength of Study is Compelling Ethics of Confirming Study Would be Questionable Application of CII (continuous insulin infusion) is Simple and Safe Hyperglycemia Predicts DSWI CII Prevents DSWI

25. 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 Examined relationship between peri-operative glucose control and risk of all infections

26. 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*

27. 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

28. 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, Ryd�n L, Hamsten A, Herlitz J, Waldenstr�m, 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, Ryd�n L, Hamsten A, Herlitz J, Waldenstr�m, 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.

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

30. ICU IV Insulin Protocol (not DKA) 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 This is not for DKAThis is not for DKA

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

32. 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 34 % reduction in hospital mortality 43 % reduction in ICU mortality Most data of ICU patients would suggest a mortality rate of 20% 63% of these were OHS patients This two year study was terminated early because the data were so robust.34 % reduction in hospital mortality 43 % reduction in ICU mortality Most data of ICU patients would suggest a mortality rate of 20% 63% of these were OHS patients This two year study was terminated early because the data were so robust.

33. Conclusion All hospital patients should have normal glucose

34. Insulin The agent we haveto control glucose

35. Methods For Managing Hospitalized Persons with Diabetes Continuous Variable Rate IV Insulin Drip Major Surgery, NPO, Unstable, MI, DKA, Hyperglycemia, Steroids, Gastroparesis Basal / Bolus Therapy when eating Teach them insulin injections

36. IV insulin protocol Not as intuitive as the Van den Berghe More agile in response to rate of change of blood sugars We do have a version of Van den Berghe available in the ICU

37. Continuous Variable Rate IV Insulin Drip 25 units Regular Insulin into 250 cc NS (0.1 unit/cc) Starting Rate Units / hour = (BG � 60) x 0.02 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)

38. 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 (one to three cc) Once eating, continue drip till 1 hour post SQ insulin This is lovely, elegant and simple. What it does is take into account the rate of change, the potential for This is lovely, elegant and simple. What it does is take into account the rate of change, the potential for

39. Example Initial glucose of 200: drip starts at 2 units per hour Glucose drops to 90, decrease drip to 0.6 units per hour If glucose instead rose to 210, the drip increases to 4.5 units per hour

40. Physiological Serum Insulin Secretion Profile This is for people without diabetesThis is for people without diabetes

41. Comparison of Insulins Insulin Onset of Duration ofpreparations action Peak action

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

43. Glargine vs NPH Insulin in Type 1 DiabetesAction Profiles by Glucose Clamp Based on euglycemic insulin clamp in normal subjectsBased on euglycemic insulin clamp in normal subjects

44. Correction Bolus�Rule of 1500 Must determine how much glucose is lowered by 1 unit of short- or rapid-acting insulin This number is known as the correction factor (CF) Use the 1500 rule to estimate the CF CF = 1500 divided by the total daily dose (TDD) ex: if TDD = 30 units, then CF = 1500/30 = 50 meaning 1 unit will lower the BG ~50 mg/dl

45. Correction Bolus Formula Example: Current BG: 220 mg/dl Ideal BG: 100 mg/dl Glucose Correction Factor: 50 mg/dl This the basis of the Baylor formula!! The baylor obviously fits no one! It works as an estimate for a total daily dose of 60 units, or about 260 pounds or 120 kilogramsThis the basis of the Baylor formula!! The baylor obviously fits no one! It works as an estimate for a total daily dose of 60 units, or about 260 pounds or 120 kilograms

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/NPH) = 40% of starting dose given at bedtime or anytime Correction bolus = (BG - 100)/ Correction Factor (CF = 1500/total daily dose)

47. How to Initiate MDI-example starting dose = 0.45 x wgt. in kg Wt is 110 kg; 0.45 x 110 = 50 units Basal dose (glargine) = 40% of starting dose at HS; 0.4 x 50 = 20 units at HS Bolus dose (aspart / lispro) = 20% of starting dose at each meal; 0.2 x 50 = 10 units ac (t.i.d.) Correction bolus = (BG - 100)/ CF, where CF = 1500/total daily dose; CF = 30 This is a starting point not gospel!! My friends in pulm/ccuThis is a starting point not gospel!! My friends in pulm/ccu

48. Correction Bolus Formula Example: Current BG: 250 mg/dl Ideal BG: 100 mg/dl Glucose Correction Factor: 30 mg/dl

49. Diabetes PlanWhat Can We Do For Patients Admitted To Hospital? Finger Stick BG ac q.i.d. on ALL Admissions Do Not Use Sliding Scale As Only Diabetes Management Check All Steroid Treated Patients Diagnose Diabetes FBG >126 mg/dl Any BG >200 mg/dl

50. Diabetes PlanWhat Can We Do For Patients Admitted To Hospital?  Get Diabetes Education Consult 449-5180 Do an A1C 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 Do Not Use Sliding Scale As Only Diabetes Management

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

52. Diabetes at HospitalConclusions 2 Type 2 Diabetes is Resistant to Insulin Reaction Do Not Hold Insulin for Normal BG A1C Values >7% Indicates Sub-optimal Care

53. Diabetes at HospitalConclusions 3 Discharge Plan For BG Control You Are the Link Between the Best Diabetes Care and the Patient Use Your Diabetes Resources Regional Diabetes Center 449-5180 Endocrinologists

54. 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 May Be Malpractice

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

56. QUESTIONS Email oatess@arnett.com Thanks to Dr. Bruce Bode

57. I need help! Searching for Diabetes Type 2 patients Drug Na�ve New category of oral agent Clinical outpatient trial Email me: oatess@arnett.com

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

60. Primary Structure of Lys(B29)-N-?-Tetradecanoyl, Des(B30)-Insulin

61. 61 Insulin Detemir in Nondiabetic Subjects�Pharmacokinetics by Glucose Clamp