Epidemiology of cardiovascular complications in diabetes mellitus.

Epidemiologic studies indicate that hyperglycaemia is responsible for micro angiopathy, but that its role in macroangiopathy is more controversial. The relative risk of coronary heart disease (CHD) is 2-to 3-fold greater for d iabetic men and 3- to 5-fold greater for diabetic women. It is greater for lower limb arteriopathy (4- to 6-fold) and amputations(10- to 20-fold). Alt hough relative risk is rather constant for different populations, absolute CHD risk depends on other risk factors and the rate of risk in the non-diab etic population. Yet hyperglycaemia is also a causal factor for CHD risk, a s demonstrated in cohort studies of Type 1 diabetic patients without diabet ic glomerulopathy or any associated CHD risk-factors, and especially in dia betic Pima Indians who are genetically protected against hypercholesterolae mia and hypertension. Finally, according to WESDR and UKPDS data, the 10-ye ar risk of cardiovascular mortality increases by 10 % for every 1 % increas e in HbA1 c value. Hyperglycaemia can be linked to atherogenesis through se veral pathways: glucooxidation of the extracellular matrix inducing acceler ated atherosclerosis, endothelial dysfunction, with a decreased production or inactivation of NO, a thrombogenic tendency, with increase in PAI1,Wille brandt factor and platelet aggregation, and last (but not least) dyslipidae mia subsequent to lipoprotein glycooxidation and increased production of VL DL. Hyperglycaemia was associated with hyperlipoproteinaemia and high plasm a triglyceride levels, low plasma HDL levels and high plasma levels of smal l and dense LDL in three high risk populations: diabetic women, Asian migra nts, and the Finnish population of Kupsio. Moreover, impaired glucose toler ance appears to be a CHD risk marker indicative of insulin resistance appar ently responsible for atherosclerosis related to an association of CHD risk factors rather than to hyperinsulinaemia. The precedence of insulin resist ance over onset of Type 2 diabetes is consistent with the existence, at dia gnosis, of clinical complications of atherosclerosis in 20 % of cases, as c onfirmed in the UKPDS study. Finally, though blood glucose control by sulph onylureas and insulin does not appear to be deleterious, these drugs have n ot shown their efficacy in reducing macrovascular adverse events in Type 2 diabetes, either because the cumulative incidence of events is inadequate ( DCCT) or the efficacy of long-term hypoglycaemic effects is not apparent (U KPDS). Moreover, these studies have shown that exogenous as well as endogen ous hyperinsulinaemia can lead to increase in weight, with potentially athe rogenic android fat distribution. In conclusion, though the correlation bet ween hyperglycaemia and microangiopathy is linear and well-established worl dwide (with every 1 % increase or decrease in HbA1c resulting in a 30 % inc rease or decrease in microangiopathic events), the same is not true for mac roangiopathy, whose prevalence is variable among populations. Thus, CHD mor tality due to diabetes is 5-fold lower in France than in Finland, though th e Monica study indicates a disparity within the French community.