The Deidesheimer meeting: significance of classical and new risk factors in non-insulin-dependent diabetes mellitus.

The major risk factors appear to explain only a small proportion of the excess risk of coronary heart disease in patients with Non-Insulin-Dependent Diabetes Mellitus (NIDDM). Among novel risk markers that have been-proposed to explain the susceptibility of NIDDM subjects to coronary heart disease are insulin resistance, elevated concentrations of proinsulin-line molecules, plasminogen activator inhibitor, and microalbuminuria. Several prospective studies have shown that hyperinsulinemia predicts coronary heart disease, perhaps independently of established risk factors. Some of this excess risk may be through the dyslipidemia, or the elevation in activity of plasminogen activator inhibitor, an inhibitor of fibrinolysis, which relate to hyperinsulinemia. However proinsulin-like molecules show similar relationships with both risk factors and with prevalent coronary heart disease as does insulin, despite low concentrations of these molecules in the circulation, suggesting a causative relationship is improbable. Furthermore, the link between insulin resistance and microalbuminuria, a powerful predictor of vascular disease in its own right, is poorly understood through known mechanisms. This clustering leads to the possibility of a link with coronary heart disease through other mechanisms. It is proposed that the pathogenesis of this link is endothelial dysfunction, which may predicate both impaired insulin action, through effects of blood flow and insulin transport, and the associated dyslipidemia, impaired fibrinolysis, microalbuminuria, and atherogenesis. In terms of etiology, the links of all these risk factors with evidence of growth retardation in early life may suggest a role of the thirfty phenotype hypothesis-impaired organogenesis resulting from poor maternal nutrition during pregnancy.