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Insulin Resistance and Cardiovascular Disease: New Perspectives From Vascular Biology

Insulin Resistance and Cardiovascular Disease: New Perspectives From Vascular Biology. Contents. I. CV disease and insulin resistance: Challenges and opportunities II. New perspectives in cardioprotection: Focus on PPAR  activation

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Insulin Resistance and Cardiovascular Disease: New Perspectives From Vascular Biology

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  1. Insulin Resistance and Cardiovascular Disease: New Perspectives FromVascular Biology

  2. Contents I. CV disease and insulin resistance: Challenges and opportunities II. New perspectives in cardioprotection: Focus on PPAR activation III. Insulin sensitizers: Surrogate and clinical outcomes studies IV. Identifying and treating patients with insulin resistance

  3. Cardiovascular Disease and Insulin Resistance:Challenges and Opportunities

  4. The majority of Americans do not follow a healthy lifestyle 2000 Behavioral Risk Factor Surveillance System; N = 153,805 100 77.8 76.7 80 59.9 60 % Respondents 40 24 20 0 Smokers BMI ≥25 kg/m2 Consumes fruits/vegetables <5x/day Infrequentexercise(<5x/week) Reeves MJ, Rafferty AP. Arch Intern Med. 2005;165:854-7.

  5. Numbers of persons with diabetes will more than double by 2030 40 118% increase 30.3 30 US population with diabetes(millions) 20 13.9 10 0 2002 2030 Year AHA. Heart Disease and Stroke Statistics–2005 Update.Wild S et al. Diabetes Care. 2004;27:1047-53.

  6. Increasing problem of obesity and diabetes among US adults Obesity (BMI ≥30 kg/m2) Diabetes 36% increase 30 8 7.2 31% increase USadults(%) 25.4 5.3 19.4 15 4 0 0 1997 2005* 1997 2005* *Jan–Sep CDC. 2005 NHIS. www.cdc.gov/nchs/nhis/released200603.htm. Accessed April 2006.

  7. Cumulative lifetime risk for diagnosis of diabetes 55 Hispanic females 50 Non–Hispanic black females Hispanic males 45 Non–Hispanic black males 40 Risk ofdiagnosisof diabetes (%) 35 Non–Hispanic white females 30 Non–Hispanic white males 25 20 15 10 5 0 0 10 20 30 40 50 60 70 80 90 100 Age (years) Adapted from Narayan et al. JAMA. 2003;290:1884-90.

  8. Over half of patients referred to cardiologists have insulin resistance syndrome Cardiac rehabilitation Acute MI 59 58 60 50 Patients withinsulin resistance syndrome (%) 40 20 0 N = 1912Savage, 2005 N = 235 Milani, 2003 N = 85 Curran, 2004 Savage PD et al. Am Heart J. 2005;149:627-31. Milani RV, Lavie CJ. Am J Cardiol. 2003;92:50-4. Curran PJ et al. J Am Coll Cardiol. 2004;43(suppl A):249A.

  9. Almost 70% of patients with first MI have IGT or undiagnosed diabetes N = 181 consecutive patients admitted to CCU 66 70 Undiagnosed diabetes 50 31 Patients (%) 30 Impaired glucose tolerance (IGT) 35 10 0 Glucose tolerance test results Norhammar A et al. Lancet. 2002;359:2140-4.

  10. Role of obesity in insulin resistance Caloric intake Sedentarylifestyle Geneticfactors Free fatty acids Glucose Lipids Oxidativestress Inflammation VisceralObesity Insulinresistance Adapted from Wellen KE, Hotamisligil GS. J Clin Invest. 2005;115:1111-9.

  11. Elevated glucose increases risk in elderly patients with acute MI Cooperative Cardiovascular Project 1994–1996; N =141,680 100 80 Mortalityrate (%) 60 40 20 0 ≤ 110 >110–140 >140–170 >170–240 >240 Glucose groups (mg/dL) Without diabetes With diabetes Kosiborod M et al. Circulation. 2005;111:3078-86.

  12. Insulin resistance associated with coronary vasomotor abnormalities Myocardial blood flow (MBF) response to cold pressor test 75 P= 0.003 50  MBF* (%) 25 0 Insulin sensitive Insulin resistant Quiñones MJ et al. Ann Intern Med. 2004;140:700-8. *vs baseline

  13. Insulin resistance to diabetes: Coronary vasomotor abnormalities progressively worsen 40 Cold pressor test 44 30  MBF* (%) † 20 14 † † 10 10 7 Diabetes + Hypertension 0 Insulinsensitive Insulinresistant IGT Diabetes –2 † –10 • *vs baseline • †P < 0.05 vs insulin sensitive Prior JO et al. Circulation. 2005;111:2291-8.

  14. Insulin resistance increases risk of target organ damage in hypertension Without insulin resistance syndrome* N = 354 with untreated hypertension P = 0.003 59 60 45 40 Patients (%) P = 0.04 30 19 15 10 0 Microalbuminuria* LV hypertrophy With insulin resistance syndrome* Leoncini G et al. J Intern Med. 2005;257:454-60. *Modified ATP III definition

  15. Clinical manifestations of insulin resistance • Type 2 diabetes and glycemic disorders • Dyslipidemia • – Low HDL • – Small, dense LDL • – Hypertriglyceridemia • Hypertension • Endothelial dysfunction/inflammation (hsCRP) • Impaired thrombolysis • PAI-1 Insulin resistance Glucotoxicity Lipotoxicity  Adiponectin VisceralObesity Atherosclerosis Courtesy of Selwyn AP, Weissman PN.

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