Insulin Delivery Systems Atlanta Diabetes Associates New Insulins and Insulin Delivery Systems Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia Part 1

Methods For Managing Persons with Diabetes Title Subtitle Methods For Managing Persons with Diabetes Take Diabetes out of the equation. Control glucose!!!

Prevalence of Glycemic Abnormalities in the United States Title Subtitle US Population: 275 Million in 2000 Undiagnosed diabetes ~5.2 million Diagnosed type 1 diabetes ~1.0 million Additional 25 -35 million with Prediabetes Diagnosed type 2 diabetes ~12 million Key Points Diabetes is highly prevalent in the United States Of the nearly 17 million people with diabetes, approximately 5.9 million are undiagnosed As the graph illustrates, diabetes and other glycemic abnormalities are highly prevalent conditions in the United States (2000 data). Recent estimates indicate that of the nearly 17 million people with diabetes in the United States, approximately 5.9 million people have undiagnosed diabetes. It is further estimated that an additional 24.6 million people, or 11% of the adults in the United States, have IGT. The incidence of diabetes is also on the rise, with a 49% increase in the number of cases diagnosed between 1990 and 2000.1-3 References Centers for Disease Control. National Diabetes Fact Sheet. Available at http://www.cdc.gov/diabetes/pubs/estimates.htm. Accessed May 9, 2002. Harris MI. Classification, diagnostic criteria, and screening for diabetes. In: National Diabetes Data Group. Diabetes in America. 2nd ed. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases; 1995:15-36. NIH Publication No. 95-1468. U.S. Census Bureau Statistical Abstract of the United States; 2001. Centers for Disease Control. Available at: http://www.cdc.gov/diabetes/pubs/estimates.htm; Harris MI. In: National Diabetes Data Group. Diabetes in America. 2nd ed. Bethesda, Md: NIDDK; 1995:15-36; U.S. Census Bureau Statistical Abstract of the U.S.; 2001 3

Diagnostic Criteria Associated with Glucose Abnormalities Title Subtitle Diagnostic Criteria Associated with Glucose Abnormalities FPG 2-Hour PG on OGTT Diabetes Mellitus Diabetes Mellitus 126 mg/dL 7.0 mmol/L 200 mg/dL 11.1 mmol/L Impaired Glucose Tolerance Prediabetes 100 mg/dL 5.6 mmol/L 140 mg/dL 7.8 mmol/L Normal Normal Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2001;24(Suppl 1):S5-S20.

Relative Risk of Progression of Diabetes Complications (DCCT) Title Subtitle RELATIVE RISK Mean A1C DCCT Research Group, N Engl J Med 1993, 329:977-986.

Lifetime Benefits of Intensive Therapy (DCCT) Title Subtitle Gain of 15.3 years of complication free living compared to conventional therapy Gain of 5.1 years of life compared to conventional therapy DCCT Study Group, JAMA 1996, 276:1409-1415.

Effect of A1C On Complications in the UKPDS Study Stratton IM et al. BMJ 2000;321:405 10 20 30 40 50 60 Myocardial Infarction Microvasc Disease 5.5% 6.5% 7.5% 8.5% 9.5% 10.5% A1C

Lessons from the DCCT and UKPDS: Sustained Intensification of Therapy is Difficult Title Subtitle DCCT EDIC (Type 1) UKPDS (Type 2), Insulin Group 10 8 Slide Index 00030 DISCUSSION POINTS: Click 1: DCCT and EDIC data in left panel: Left panel shows data from a sub-group of patients who had been in the intensive group during the DCCT and continued in EDIC, a long-term follow-up of the DCCT This sub-group began the DCCT with an average HbA1c of 9.0% [first bar], and ended the study with a mean of 7.3% [second bar]. After the DCCT ended, patients returned to community-based diabetes management and were followed for an additional 4 [third bar, blue] and 6 [last bar, blue] years. As can be seen by the increasing HbA1c in the last 2 blue bars, these patients had difficulty sustaining HbA1c improvements achieved during the DCCT. Click 2: UKPDS data appears in right panel The right panel shows data from the insulin-treated group of the UKPDS. Initial decreases in HbA1c were not sustained during the 10-year study period. SLIDE BACKGROUND: EDIC: Epidemiology of Diabetes Interventions and Complications 1375 of the 1441 DCCT participants (95%) volunteered to participate in EDIC. 1208 patients were evaluated after 4 years of follow-up in EDIC (605 of these were previously in the DCCT intensive group; N for Year 6 not yet available). Data for DCCT/EDIC on slide are for previous participants in DCCT intensive group. The gap between this group and their counterparts in the conventional group has diminished over time. Data for previous participants in DCCT conventional group are: DCCT time 0 = 9.0% DCCT time 6.5 yrs = 9.0% EDIC + 4 years = 8.2% EDIC + 6 years = 8.1% Data for DCCT/EDIC are means. 9.0 8.1 8 7.9 7.3 A1C (%) A1C (%) 7 Baseline 6 6 Normal 4 6.5 + 4 + 6 yrs 2 4 6 8 10 yrs DCCT EDIC DCCT/EDIC Research Group. New Engl J Med 2000; 342:381-389 Steffes M et al. Diabetes 2001; 50 (suppl 2):A63 UK Prospective Diabetes Study Group (UKPDS) 33 Lancet 1998; 352:837-853

Specific Goals in Management of Diabetes Title Subtitle Specific Goals in Management of Diabetes Fasting < 110 mg/dL Post-meal < 140 mg/dL A1C < 6.5% Blood Pressure < 130/80 LDL < 100 mg/dL; HDL > 45 mg/dL Triglycerides < 150 mg/dL

Primary Objectives of Effective Management Title Subtitle Primary Objectives of Effective Management lGæde P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-393. Diagnosis 9 A1C % 8 7 Reduction of both micro- and macro- vascular event rates …by 75%! SBP mm Hg 145 130 LDL mg/dL Key Points The primary objectives of effective diabetes management are to reduce A1C to as near-normal levels (ie, 4%–6%) as is possible and safe, to lower systolic blood pressure to <130 mm Hg, and to decrease LDL cholesterol to <100 mg/dL Achieving target levels of A1C, systolic blood pressure, and LDL cholesterol may reduce the risk of the micro- and macrovascular complications of diabetes by up to 75% As illustrated in this slide, the objectives of effective diabetes management are to reduce A1C to as near-normal levels as is possible and safe (ie, 4%–6%), lower systolic blood pressure to <130 mm Hg, and to decrease LDL cholesterol to <100 mg/dL. Evidence suggests that achieving these target levels can reduce the risk of both microvascular and macrovascular complications of diabetes by >75%.1 Most recently, the Steno-2 Study followed 160 patients with type 2 diabetes and microalbuminuria over 7.8 years to determine the effect of intensive treatment on long-term CV and microvascular outcomes. Researchers found that target-driven, intensive treatment consisting of stepwise diet, exercise, and pharmacotherapy for glycemia, microalbuminuria, lipids, and blood pressure resulted in a decreased risk of CV and microvascular events of about 50%. Control group members received conventional treatment in accordance with national guidelines. However, factors leading to diminished degrees of separation between the intensive treatment and control groups (eg, more than 50% of control group members were referred for specialist treatment during the course of the study) led the authors to estimate that the actual risk reduction associated with intensive versus conventional therapy may be even greater than that observed.2 References American Diabetes Association. Clinical Practice Recommendations. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 2003;26(suppl 1):S28-S32. Gæde P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-393. 140 100 45 50 55 60 65 70 75 80 85 90 Patient Age

Mortality of DM Patients Undergoing CABG Furnary et al J Thorac Cardiovasc Surg 2003;123:1007-21

Surgical ICU Mortality Effect of Average BG Van den Berghe et al (Crit Care Med 2003; 31:359-366) P=0.0009 BG>150 110<BG<150 P=0.026 BG<110

Hyperglycemia and Hospital Mortality 1826 consecutive ICU patients 10/99 thru 4/02, Stamford CT Krinsley JS: Mayo Clin Proc 78: 1471-1478, 2003