MICROALBUMINURIA - A GENETIC LINK BETWEEN DIABETES AND CARDIOVASCULAR-DISEASE

Non-insulin-dependent diabetes is associated with a 2-3 fold increased risk of cardiovascular disease. The poor relationship between this risk and either glycaemic control or diabetes duration suggests that some other aspect of the diabetic state, and not hyperglycaemia per se, mediates this risk. This other aspect of diabetes does not comprise alterations in recognized cardiovascular risk factors such as blood pressure or lipids, as the major component of the excess risk is in those diabetics with low levels of the other risk factors. It thus appears that there may be some factors that predispose both to diabetes and to cardiovascular disease. In insulin-dependent diabetics most of the excess risk of cardiovascular disease occurs in subjects with proteinuria, and microalbuminuria or proteinuria in non-insulin-dependent diabetics also substantially increases cardiovascular risk. Although changes in recognized risk factors in diabetics with nephropathy may partly explain these observations, we and others have shown that microalbuminuric non-diabetics also have a markedly increased prevalence of cardiovascular disease and substantially increased cardiovascular mortality. The observations that in insulin-dependent diabetics nephropathy shows family clustering and that these patients have elevated sodium lithium counter-transport rate, a possible genetic marker for the vascular complications of hypertension, have led to the suggestion that microalbuminuria may be a marker of a genetic predisposition to vascular disease. However, in a recent population study, we have found that microalbuminuric men are substantially shorter than normoalbuminuric men, raising instead the possibility that early environmental influences, in utero or in early neonatal life, may predispose to microalbuminuria in similar fashion to recent work which has associated low fetal and neonatal growth rate with both diabetes and other cardiovascular risk factors. Future work may determine the respective genetic and environmental contributions to microalbuminuria and to cardiovascular risk.