Coronary heart disease in diabetes mellitus: three new risk factors and a unifying hypothesis

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Abstract
The standard risk factors--dyslipidaemia, hypertension and smoking--provide little help in explaining the raised cardiovascular risk in diabetes. It can be calculated that intervening for disturbances of these risk factors could do little to rectify the loss of life expectancy of around 10 years for a middle-aged diabetic man. Three new risk factors are discussed, which together may contribute to some of the excess cardiovascular risk in diabetes. Plasminogen activator inhibitor is an inhibitor of fibrinolysis which is elevated in concentration in diabetic subjects, and may increase both the incidence of thrombotic events and the risk of reinfarction after the initial infarct. Recent work also suggests that high activity of this substance may impair pharmacological fibrinolysis. Proinsulin-like molecules are elevated in concentration in diabetic patients and correlate with levels of a number of other risk factors. Whilst these correlations may represent cause and effect for plasminogen activator inhibitor, there is no evidence that changes in levels of proinsulin-like molecules influence levels of other risk factors. Microalbuminuria provides a powerful indicator of cardiovascular risk in both diabetic and non-diabetic subjects, but whilst the mechanisms for this association are unclear, they are again unlikely to be mediated through changes in levels of standard risk factors. Recent observations of an association between short stature and microalbuminuria suggest that intrauterine or early infant nutrition may represent a common antecedent, these having also been shown to predict both components of the insulin resistance syndrome and cardiovascular disease in adult life.