23. Odds Ratios for IHD According to Plasma Insulin and Lipids Després J-P et al. N Engl J Med . 1996;334:952-957. <12 12-15 >15 Total:HDL-C ratio Insulin ( U/mL) 1.0 3.4 ‡ 4.3 § 7.1 † 10.3 † 9.6 † Low High 0 3 6 9 12 <12 12-15 >15 Apo B Insulin ( U/mL) Odds ratio 1.0 1.8 3.0* 3.2* 9.7 † 11.0 † * P =0.04; † P <0.001; ‡ P =0.05; § P =0.01. IHD=ischemic heart disease. Low High 0 3 6 9 12
24. IRAS: Negative Association Between Insulin Sensitivity and Atherosclerosis Howard G et al. Circulation . 1996;93:1809-1817. Reduction in mean ICA IMT ( m per 1-unit increase in S i After adjustment for demographics. IRAS=Insulin Resistance Atherosclerosis Study. 20 10 0 -10 -20 -30 -40 Non-Hispanic White Hispanic African American -30.1 -29.9 6.1
27. Dyslipidemia and Insulin Resistance: Mechanisms (CETP) (lipoprotein or hepatic lipase) Fat cells Insulin IR FFA Liver (CETP) CE TG Apo A-I CE TG LDL TG Apo B VLDL Kidney (hepatic lipase) CE=cholesterol ester; CETP=cholesterol ester transfer protein. VLDL HDL SD LDL
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33. Nitric Oxide–Mediated Vasodilation Is Impaired in Type 2 Diabetes 0 2 4 6 8 10 12 Baseline 0.3 1 3 10 Methacholine chloride ( g/min) No diabetes (23) Diabetes (21) Difference in forearm blood flow (mL/min/100 mL) Modified from Williams SB et al. J Am Coll Cardiol . 1996;27:567-574. * P <0.005. *
34. Impaired Macrovascular Reactivity in People at Risk for Type 2 Diabetes Caballero AE et al. Diabetes. 1999;48:1856-1862. *C vs R, IGT, and D, P <0.01. 13.7* 10.5 9.8 8.4 Increase over baseline after cuff occlusion (%) Controls (C) Relatives (R) IGT Diabetes (D)
35. Impaired Microvascular Reactivity in People at Risk for Type 2 Diabetes Caballero AE et al. Diabetes. 1999;48:1856-1862. *C vs R, IGT, and D, and R vs D, P <0.001. Increase over baseline after cuff occlusion (%) 0 100 200 Acetylcholine Sodium nitroprusside 126* 98* 94 74 123* 85* 83 65 Controls (C) Relatives (R) IGT Diabetes (D)
36. Oxidative Stress in the Development of CVD in Diabetes Rösen P et al. Diabetes Metab Res Rev . 2001;17:189-212. LDL Oxidized LDL Macrophages overloaded with oxidized LDL Increased MI rate Decreased plaque stability Atherogenic plaques Foam cells in arterial walls Modulation of transcription factors Hyperglycemia Free radicals
37. IRAS: Relation of C-Reactive Protein to Insulin Sensitivity Festa A et al. Circulation . 2000;102:42-47. Low Middle High Insulin sensitivity tertile 0.05 0.25 1.22 6.05 30.0 Log CRP (mean values) IRAS = Insulin Resistance Atherosclerosis Study.
38. Relation of C-Reactive Protein to Insulin Sensitivity Festa A et al. Circulation . 2003;108:1822-1830. CRP (mg/L) High resistance Low secretion Non-converters High resistance vs low secretion, P =0.005 High resistance vs nonconverters, P <0.0001 Low secretion vs nonconverters, P =NS
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43. AGEs and the Severity of Coronary Arteriosclerosis in Diabetes 0 4 8 12 Single vessel Two vessel Three vessel AGE (mU/mL) P <0.017 P <0.017 Kiuchi K et al. Heart . 2001;85:87-91. AGE=advanced glycation end-products.