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Diabetes – A 21st Century Epidemic Diagnosis and what is it A common disease An expensive disease A serious disease A treatable disease A preventable disease Diagnosis and what is it Glucose Tolerance Categories FPG 2-Hour PG on OGTT Diabetes Mellitus Diabetes Mellitus 126 mg/dL 100 mg/dL 7.0 mmol/L Impaired Fasting Glucose Normal 5.7 mmol/L 200 mg/dL 140 mg/dL 11.1 mmol/L Impaired Glucose Tolerance 7.8 mmol/L Normal Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197. What is it ? Diabetes is a Vascular Disease % Affected Background Retinopathy 100 125 150 175 200 Fasting Plasma Glucose Natural History of Type 2 Diabetes Post-meal glucose 350 Gluco 300 250 se (mg/d 200 150 L) 100 Diabetes IGT Fasting glucose -15 -10 -5 0 5 10 125 Relative 100 Functio 75 n (%) 50 25 0 15 20 25 Insulin resistance ß-cell -15 -10 -5 0 5 10 Years of Diabetes Adapted from: International Diabetes Center (Minneapolis, 15 20 25 Etiologic Classification of Diabetes Mellitus Type 1 b-cell destruction with lack of insulin Type 2 Insulin resistance with insulin deficiency Other specific types Genetic defects in b-cell function, exocrine pancreas diseases, endocrinopathies, drug- or chemicalinduced, and other rare forms Gestational Insulin resistance with b-cell dysfunction Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197. Diabetes in the U.S. • 23.6 million (10.7% ≥ 20 y.o) at a cost of $174 billion in 2007 – 57 million with prediabetes • 6th disease specific cause of death. • Leading cause of: – Kidney failure. – Adult blindness. – Nontraumatic limb amputation. – Cardiovascular disease. ADA. Diabetes Care 31:596-615, 2008 Diabetes is a Common Disease : Estimated Prevalence of Diabetes in the US: Adult Men and Women Percent of Population 30 Men Women 21.1 20.2 20 17.8 17.5 12.9 12.4 10 6.8 6.1 1.6 1.7 0 20-39 40-49 Harris, et al. Diabetes Care. 1998;21:518-524, with permission. 50-59 Age (y) 60-74 75+ Estimated Prevalence of Diabetes in the US: Breakdown by Ethnicity 10 9.3 Diagnosed Percent of Population 8.2 Undiagnosed 8 6 4.8 4.5 3.6 4 2.5 2 0 Non-Hispanic White Data from Harris, et al. Diabetes Care. 1998;21:518-524. African American Hispanic American Diabetes – An expensive disease Direct and indirect costs of diabetes estimated to be $174 Billion annually in the USA in 2007 Costs to most health systems is 2-3 fold greater annually for patients with diabetes 1997 Per Capita Health Care Costs: Persons With and Without Diabetes 25 23.5 Diabetes Annual Costs ($1000s) No diabetes 20 15 12.2 10 5 0 2.5 Inpatient 1.5 Outpatient Services 0.7 0.4 ER Data from American Diabetes Association. Diabetes Care. 1998;21:296-309. 0.7 0.4 Office Visits 0.7 0.2 Outpatient Drugs Diabetes – A serious but treatable disease Microvascular complications Blindness, renal failure and nerve dysfunction Macrovascular complications Atherosclerosis –MI, Stroke and amputations Hypertension - Stroke, CHF, CAD The Arterial Tree in Diabetes Conduit Artery Resistance Arterioles Atherosclerosis Hypertension Precapillary Capillaries Arterioles Retinopathy Neuropathy Nephropathy Framingham Heart Study 30-Year Follow-Up: CVD Events in Patients With Diabetes (Ages 35-64) 10 10 9 Men 8 Risk ratio Women 11 6 4 30 19 38 9 20 2 6 3* 0 Total CVD CHD Cardiac failure Intermittent Stroke claudication Age-adjusted annual rate/1,000 P<0.001 for all values except *P<0.05. Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease. Ruderman N et al, eds. Oxford; 1992. Women, Diabetes, and CHD • Diabetic women are at high risk for CHD • Diabetes eliminates relative cardioprotective effect of being premenopausal – risk of recurrent MI in diabetic women is three times that of nondiabetic women • Age-adjusted mean time to recurrent MI or fatal CHD event is 5.1 yr for diabetic women vs 8.1 yr for nondiabetic women Kannel WB. Am Heart J. 1985;110:1100-1107. Abbott RD et al. JAMA. 1988;260:3456-3460. Atherosclerosis in Diabetes • ~80% of all diabetic mortality – 75% from coronary atherosclerosis – 25% from cerebral or peripheral vascular disease • >75% of all hospitalizations for diabetic complications • >50% of patients with newly diagnosed type 2 diabetes have CHD National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995. 4S: Major CHD Event Reduction in a Patients With Diabetes 1.00 5.00 0.90 4.00 0.80 Proportion 3.00 32% without 0.70 major CHD 2.00 event Diabetic, simvastatin - P=0.002 0.60 1.00 Diabetic, placebo 0.50 0.00 Nondiabetic, placebo 55% Nondiabetic, simvastatin 0 1 2 3 - P=0.0001 4 Yr since randomization Pyörälä K et al. Diabetes Care. 1997;20:614620. 5 6 The Arterial Tree in Diabetes Conduit Artery Resistance Arterioles Atherosclerosis Hypertension Precapillary Capillaries Arterioles Retinopathy Neuropathy Nephropathy UKPDS Blood Pressure Control blood pressure control reduced risk for Any diabetes-related endpoint diabetes-related deaths stroke microvascular disease heart failure retinopathy progression deterioration of vision 24% 32% 44% 37% 56% 34% 47% p=0.0046 p=0.019 p=0.013 p=0.0092 p=0.0043 p=0.0038 p=0.0036 Diabetes and CHD • HOPE Study – 9297 pts >55y.o. with DM or vascular disease + 1 CVD risk factor (~3578 DM ) – Placebo or Ramipril 10 mg qd followed ~ 4 yrs – Significant reductions in cardiovascular events (MI, stroke and CV death) – Changes seen in both DM and non-DM groups MICRO-HOPE • No clinical proteinuria, CHF or diminished EF and not on ACE. • 3577 patients with DM and either known CHD or one additional risk factor. • Ramapril 10 mg/d or placebo. • Study stopped at 4.5 yrs by DSMB ACE Inhibition in DM Hope Trial Ramipril Placebo (n=1808) (n=1769) P Combined 277 351 .0004 MI 185 229 .01 Stroke 76 108 .007 CV Death 112 172 .0001 The Arterial Tree in Diabetes Conduit Artery Resistance Arterioles Atherosclerosis Hypertension Precapillary Capillaries Arterioles Retinopathy Neuropathy Nephropathy Glucose Control Study Summary The intensive glucose control policy maintained a lower HbA1c by mean 0.9 % over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk of: 12% 25% for any diabetes related endpoint for microvascular endpoints 16% 24% for myocardial infarction for cataract extraction 21% 33% for retinopathy at twelve years for albuminuria at twelve years p=0.029 p=0.0099 p=0.052 p=0.046 p=0.015 p=0.000054 Quality of Life: Effect of Improved Glycemic Control 0.4 P<.001 Improved 0.3 P<.01 P<.01 P<.05 0.2 0.1 0 -0.1 -0.2 Worsened -0.3 Quality-of-Life Mental Analog Rating Health Cognitive Function Testa & Simonson, JAMA, 1998;280;1490-1496. General Perceived Health Symptom Distress Placebo Extendedrelease glipizide Glucose Control and Costs of Care A 6 year comparison between patients who improved glucose control (decline in HgbA1C >1%) or not has shown that improved glycemic control reduced annual health care costs for affected individuals Reductions due to fewer physican and emergency room visits Cost saving of $600-1000 annually. Diabetes a preventable disease Several trials of diabetes prevention have been conducted for type 1 diabetes using vaccine strategies. None have yet been successful For Type 2 diabetes, multiple trials successfully demonstrated that both lifestyle changes and pharmacologic interventions can delay or prevent diabetes among individuals at high risk Prevention of DM 2 F/U DM Incidence Risk Reduction Study Control Da Qing 6 Yr 68% Diet Exercise 44% DPS 4 Yr 23% 11% 58% DPP 3 Yr 29% 14% 58% 31% Prevention of Diabetes with Lifestyle Modification Effect of Metformin and Lifestyle Modification on New Onset Diabetes - Lifestyle changes work better as we age % Decline in Diabetes Incidence 80 70 60 50 Metformin Lifestyle 40 30 20 10 0 25-44 44-59 Subject Age >59 Okinawa • • • • • 161 island archipelago, most live on main island, pop 1.3 m “Galapagos of the East” Lowest age-adjusted mortality (CHD, stroke, cancer) Longest disability-free life expectancy of 47 Japanese prefectures (states) Highest centenarian prevalence Centenarians in the World (by prevalence) Willcox DC et al AGE 2006 Diabetes – A model for intervention in chronic disease • As the population ages: – Diabetes becomes more common – Diabetes itself is more preventable by a healthy lifestyle – Complications of diabetes while common can be prevented Ushi Okushima 106 Years Young and Still Diggin’ Life Domo Arigato! 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