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Diabetes – A 21 st Century Epidemic

Diabetes – A 21 st Century Epidemic. Diagnosis and what is it A common disease An expensive disease A serious disease A treatable disease A preventable disease. FPG. 2-Hour PG on OGTT. Diabetes Mellitus. Diabetes Mellitus. 126 mg/dL. 7.0 mmol/L. 200 mg/dL. 11.1 . mmol/L.

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Diabetes – A 21 st Century Epidemic

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  1. 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

  2. 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 Fasting Impaired Glucose Glucose Tolerance 100 mg/dL 5.7 mmol/L 140 mg/dL 7.8 mmol/L Normal Normal Diagnosis and what is itGlucose Tolerance Categories Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197.

  3. What is it ?Diabetes is a Vascular DiseaseBackground Retinopathy % Affected • 100 125 150 175 200 • Fasting Plasma Glucose

  4. 350 300 250 200 150 100 125 100 75 50 25 0 -15 -10 -5 0 5 10 15 20 25 Natural History of Type 2 Diabetes Post-meal glucose Diabetes IGT Glucose (mg/dL) Fasting glucose -15 -10 -5 0 5 10 15 20 25 RelativeFunction (%) Insulin resistance ß-cell Years of Diabetes Adapted from: International Diabetes Center (Minneapolis, Minnesota).

  5. 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, endo- crinopathies, drug- or chemical- induced, 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.

  6. 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

  7. Diabetes is a Common Disease : Estimated Prevalence of Diabetes in the US:Adult Men and Women 30 Men Women 21.1 20.2 20 17.8 17.5 Percent of Population 12.9 12.4 10 6.8 6.1 1.6 1.7 0 20-39 40-49 50-59 60-74 75+ Age (y) Harris, et al. Diabetes Care. 1998;21:518-524, with permission.

  8. Estimated Prevalence of Diabetes in the US:Breakdown by Ethnicity 10 9.3 Diagnosed 8.2 Undiagnosed 8 6 Percent of Population 4.8 4.5 3.6 4 2.5 2 0 Non-Hispanic African Hispanic White American American Data from Harris, et al. Diabetes Care. 1998;21:518-524.

  9. 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

  10. 1997 Per Capita Health Care Costs:Persons With and Without Diabetes 25 23.5 Diabetes No diabetes 20 15 12.2 Annual Costs ($1000s) 10 5 2.5 1.5 0.7 0.7 0.7 0.4 0.4 0.2 0 Inpatient Outpatient ER Office Outpatient Services Visits Drugs Data from American Diabetes Association. Diabetes Care. 1998;21:296-309.

  11. 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

  12. The Arterial Tree in Diabetes Conduit Artery Resistance Precapillary Capillaries Arterioles Arterioles AtherosclerosisHypertension Retinopathy Neuropathy Nephropathy

  13. Framingham Heart Study 30-Year Follow-Up:CVD Events in Patients With Diabetes (Ages 35-64) 10 10 9 Men Women 8 11 Risk ratio 6 30 19 4 38 9 6 20 3* 2 0 Intermittent claudication Total CVD CHD Cardiac failure Stroke 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.

  14. 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.

  15. 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.

  16. 4S: Major CHD Event Reduction in a Patients With Diabetes Proportionwithoutmajor CHD event 32% Diabetic, simvastatin - P=0.002 Diabetic, placebo 55% Nondiabetic, simvastatin - P=0.0001 Nondiabetic, placebo Yr since randomization Pyörälä K et al. Diabetes Care. 1997;20:614-620.

  17. The Arterial Tree in Diabetes Conduit Artery Resistance Precapillary Capillaries Arterioles Arterioles Atherosclerosis Hypertension Retinopathy Neuropathy Nephropathy

  18. UKPDS Blood Pressure Control blood pressure control reduced risk for Any diabetes-related endpoint 24% p=0.0046 diabetes-related deaths 32% p=0.019 stroke 44% p=0.013 microvascular disease 37% p=0.0092 heart failure 56% p=0.0043 retinopathy progression 34% p=0.0038 deterioration of vision 47% p=0.0036

  19. 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

  20. 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

  21. ACE Inhibition in DM

  22. The Arterial Tree in Diabetes Conduit Artery Resistance Precapillary Capillaries Arterioles Arterioles Atherosclerosis Hypertension Retinopathy Neuropathy Nephropathy

  23. 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% for any diabetes related endpoint p=0.029 • 25% for microvascular endpoints p=0.0099 • 16% for myocardial infarction p=0.052 • 24% for cataract extraction p=0.046 • 21% for retinopathy at twelve years p=0.015 • 33% for albuminuria at twelve years p=0.000054

  24. Quality of Life: Effect of Improved Glycemic Control P<.001 Improved P<.01 Extended- release glipizide P<.01 P<.05 Worsened General Perceived Health Quality-of-Life Analog Rating Mental Health Cognitive Function Symptom Distress Testa & Simonson, JAMA, 1998;280;1490-1496.

  25. 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.

  26. 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

  27. Prevention of DM 2

  28. Prevention of Diabetes with Lifestyle Modification

  29. Effect of Metformin and Lifestyle Modification on New Onset Diabetes - Lifestyle changes work better as we age % Decline in Diabetes Incidence Subject Age

  30. 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

  31. Centenarians in the World (by prevalence) Willcox DC et al AGE 2006

  32. 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

  33. Ushi Okushima 106 Years Young and Still Diggin’ Life Domo Arigato! Thank you !

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