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In people with diabetes:

Diabetes Mellitus: A state of premature cardiovascular death which is associated with chronic hyperglycemia and may also be associated with blindness and renal failure. Fisher BM. Diabetes Mellitus and myocardial infarction: a time to act or a time to wait? Diabetes Medicine. 1998, 15: 275.

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In people with diabetes:

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  1. Diabetes Mellitus: A state of premature cardiovascular death which is associated with chronic hyperglycemia and may also be associated with blindness and renal failure. Fisher BM. Diabetes Mellitus and myocardial infarction: a time to act or a time to wait? Diabetes Medicine. 1998, 15: 275

  2. Diabetes and CVD • In people with diabetes: • Heart disease strikes people with diabetes, twice as often as people without diabetes. • CVS complications occur at an earlier age and often result in premature death. • Diabetics are 2-4 times more likely to suffer strokes and once having had a stroke, are 2-4 times as likely to have a recurrence. • Deaths from heart disease in diabetic women have increased 23 %over the past 30 years compared to a 27 % decrease in women without diabetes. • Deaths from heart disease in men with diabetes have decreased by only 13 % compared to a 36 % decrease in men without diabetes.

  3. Glycemia Is a Cardiovascular Risk Factor: Plausible Biochemical Mechanisms

  4. Haffner Study 1998

  5. Haffner Study • Conclusions Our data suggest that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as nondiabetic patients with previous myocardial infarction. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in nondiabetic patients with prior myocardial infarction.

  6. CDV Events in Diabetes Patients: Framingham Study

  7. FPG and 2 – h Pg Predict Mortality in Persons Not Known to Have Type 2 Diabetes DECODE Study

  8. Relation between postprandial blood glucose levels and cardiovascular mortality

  9. DECODE: IGT Increases Mortality Risk Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe

  10. Hba1c Predicts MI in Type 2 Diabetes UKPDS 35

  11. Ticking Clock Hypothesis: Glucose Abnormalities Increase CV Risk Nurses Health Study, N=117.629 women, aged 30- 55 years follow – up 20 `years (1976 – 1996)

  12. Pathogenesis of Increased CVD in Diabetes • Metabolic Factors Hyperglycemia Lipids , lipoproteins FFA, insulin resistance • Hypertension

  13. Role of HYPERGLYCEMIA

  14. Hyperglycemia and Vascular Disease: Pathogenesis • Many aspects of coagulation impaired • Platelet behaviour abnormal: • Hypersensitive to stimuli • Clot lysis inhibited: • Higher Plasminogen activator inhibitor 1 levels • Fibrinogen levels elevated; Disordered kinetics

  15. Is it only Hyperglycemia?

  16. Insulin resistance

  17. Insulin resistance – the link between CVD and type 2 diabetes • Insulin resistance is an independent predictor of CVD2 • Insulin resistance is closely linked to a number of CVD risk factors3 • Insulin resistance may develop 20+ years before onset of type 2 diabetes:4 ~50% of newly diagnosed patients show signs of CVD5 • NCEP recognises type 2 diabetes as a coronary heart disease risk equivalent6 2Bonora E, et al. Diabetes Care 2002;25:1135–1141. 3Bonora E, et al. Diabetes 1998;47:1643–1649. 4Beck-Nielsen H & The EGIR. Drugs 1999;58(Suppl. 1):7–10. 5Laakso M. Int J Clin Pract Suppl 2001;121:8–12.6NCEP ATP III. JAMA 2001;285:2486–2497.

  18. Insulin resistance is linked to a range of CVD risk factors Insulin resistance Endothelial dysfunction Dyslipidaemia Hypertension Microalbuminuria Vascular inflammation Atherosclerosis CVD Adapted from McFarlane SI, et al. J Clin Endocrinol Metab 2001;86:713–718.

  19. Insulin resistance is an independent predictor of CVD in type 2 diabetes: The Verona Diabetes Complications Study 2.5 * * 2.0 1.5 * Odds ratio (95%) for incident CVD * 1.0 0.5 0.0 Insulin Smoking (yes vs. no) TC:HDL Age resistance (per unit) (per year) (per unit) Error bars = 95% CI *P < 0.001; n = 627 Adapted from Bonora E, et al.Diabetes Care 2002;25:1135–1141.

  20. Endothelial dysfunction correlates with insulin resistance 12 Control Type 2 diabetes Hypertension 10 8 Whole-body insulin sensitivity (MCR; ml/kg/min) 6 4 2 0 –20 0 20 40 60 Vasoreactivity (change in forearm blood flow ratio [%]) n = 27 r = 0.46, P < 0.05 Adapted from Cleland SJ, et al. Hypertens 2000;35:507–511.

  21. Low HDL is associated with hyperinsulinaemia 60 Hyperinsulinaemic Normoinsulinaemic 50 * * HDL-c (mg/dl) 40 30 20 Non-obese Obese Error bars = SE Adapted from Reaven GM. In: Diabetes Mellitus. LeRoith D et al., eds. Philadelphia: Lippincott-Raven; 1996:509–519. *P < 0.005

  22. Proportion of small dense LDL is associated with insulin resistance * (n = 52) (n = 29) (n = 19) Error bars = SD Mean (± SD) LDL diameter (Å): pattern A = 268 ± 4; intermediate = 261 ± 3; pattern B = 250 ± 4*P < 0.005–0.001 compared with pattern A or intermediate pattern Adapted from Reaven GM, et al. J Clin Invest 1993;92:141–146.

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