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Diabetes Update Glycemic Control Raymond O. Estacio, MD Denver Health Associate Professor of Medicine University of Colorado, Denver School of Medicine Director of Medical Affairs, Colorado Prevention Center

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Why are We Concerned about Diabetes? Every 24 hours... 3,600 new cases of diabetes are diagnosed 3,600 new cases of diabetes are diagnosed 580 people die of diabetes-related complications 580 people die of diabetes-related complications 225 people have a diabetes-related amputation 225 people have a diabetes-related amputation 120 people with diabetes progress to end-stage renal disease 120 people with diabetes progress to end-stage renal disease 55 people with diabetes become blind 55 people with diabetes become blind www.diabetes.orb

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Increasing Prevalence of Diagnosed Diabetes in US Adults 19942005

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The Burden of Diabetes in the United States 21 million Americans have diabetes 21 million Americans have diabetes 6 th leading cause of death in the US (225,000) 6 th leading cause of death in the US (225,000) Direct and indirect cost = $174 billion Direct and indirect cost = $174 billion Diabetes accounts for 19% of health care expenditures in the US Diabetes accounts for 19% of health care expenditures in the US Source: American Diabetes Association

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ADA, Diabetes Care. 2003;26:917-932 Projected Increase in the US Population with Diagnosed Diabetes by 2020 by Ethnicity

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Diabetic Complications Complications of diabetes include: Complications of diabetes include: Cardiovascular Disease Cardiovascular Disease Heart Attacks Heart Attacks Stroke Stroke Heart Failure Heart Failure Renal Disease Renal Disease Retinopathy Retinopathy Neuropathy Neuropathy

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Reduction in Life Expectancy According to Age at Time of Diagnosis Years Roper et al, BMJ 2001

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Ischemic heart disease % of Deaths Geiss LS et al. In: Diabetes in America. 2 nd ed. 1995; chap 11. Mortality in People with Diabetes Causes of Death Other heart disease Diabetes CancerStroke Infection Other

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Trends in Mortality Rates for CVD in NHANES Subjects with and without Diabetes Gregg et al., Ann Inttern Med 2007 Progress in reducing mortality rates among persons with diabetes has been limited to men. Diabetes continues to greatly increase the risk for mortality, particularly among women. Mortality rates are calculated as annual deaths per 1000 persons

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Glycemic Control in Type 2 Diabetes

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Glycemic Control on Diabetic Microvascular Complications Type 2 UKPDS 8 7% 17-21% 24-33% - HbA1c Retinopathy Nephropathy Neuropathy Type 1 DCCT 9 7% 76% 54% 60% Type 2 Kumamoto 9 7% 69% 70% - DCCT Research Group, NEJM 1993, Ohkubo et al., Diab Res Clin Pract 1995, UKPDS Group, Lancet 1998

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Glycemic Control and Diabetic Macrovascular Complications Epidemiologic data demonstrating a 2 4x increased in CVD outcomes Epidemiologic data demonstrating a 2 4x increased in CVD outcomes Blood Sugar Related to Lipoproteins, Syndrome X, Clotting, AGE, Renal Disease Therefore, improved glycemic control over a long period of time should lead to a decrease in CVD outcomes?

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Veterans Affairs Diabetes Feasibility Study 150 patients over 2 years Randomized to Standard versus Intensive therapy 2.07% separation of glycosylated hemoglobin (HbA1c) 61 new cardiovascular events 32% intensive treatment 20% standard treatment (P =.10). Intensive Standard Abraira et al., Arch Int Med 1997

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UKPDS 3800 newly diagnosed type 2 DM patients Randomized to Intensive versus Standard therapy Over 10 years of follow up A1C 7% vs 8%

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UKPDS Aggregate endpoints by treatments EndpointIntensiveConventionalRR for Intensive Treatment (N=2729) (N=1138) Any diabetes endpoint 963 438 0.88 (0.79-0.99) Diabetes-related death 285 129 0.90 (0.73-1.11) All-cause mortality 489 213 0.94 (0.8-1.10) MI 387 186 0.84 (0.71-1.00) Stroke 148 55 1.11 (0.81-1.51) Amputation/ PVD death 29 18 0.65 (0.36-1.18) Microvascular 225 121 0.75 (0.60-0.93) UKPDS Group, Lancet 1998

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DCCT/EDIC Metabolic Results DCCT Intervention DCCT Intervention S t u d y Y e a r DCCT 1 2 3 4 5 6 7 8 9 EDIC Observation EDIC ObservationTraining EDIC Conventional EDIC mean 8.2% Intensive EDIC mean 8.0% DCCT/EDIC Study Research Group, NEJM 2005

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Conventional Intensive Non-Fatal MI, Stroke or CVD Death Cardiovascular Events 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Number at Risk Intensive: 705 686 640 118 Conventional: 721 694 637 96 Years from Study Entry 0.00 0.02 0.04 0.06 0.08 0.10 0.12 Cumulative Incidence Risk reduction 57% 95% CI: 12, 79 Log-rank P = 0.018 DCCT/EDIC Study Research Group, NEJM 2005

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Recent Studies Evaluating Glycemic Control on CVD ACCORD ACCORD ADVANCE ADVANCE VADT VADT

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ACCORD: Study design ACCORD Study Group. Am J Cardiol. 2007;99(suppl):21i-33i. www.accordtrial.org *Statin + fibrate vs statin, treatment group assignment blinded until end of trial Primary outcome: CV death, MI, stroke Glycemia trial N = 10,251 with T2DM and existing CVD or additional CV risk factors 1178 1184 1193 1178 1383 1370 1374 1391 5128 5123 2362237127532765 SBP