Insulin-resistance syndrome and cardiovascular complications of non-insulin-dependent diabetes mellitus

Although most cohort studies have shown that diabetes is a risk factor for cardiovascular disease, the mechanisms remain unclear. Hyperglycaemia defines this disorder but does not provide the criteria for causality. However, there are new indications for the possible role of a potentially atherogenic and diabetogenic syndrome rooted in insulin resistance, which was first described by Reaven as ''syndrome X''. In its complete form, this syndrome includes hyperinsulinaemia, glucose intolerance, dyslipidaemia, elevated blood pressure and fibrinolytic impairment. The complex pathophysiological processes leading to the clustering of these abnormalities are still unclear but probably relate to excessive intra-abdominal fat deposits (clinically expressed by upper body fat distribution) and combined insulin resistance and hyperinsulinaemia. The presence of insulin resistance and hyperinsulinaemia in pre-diabetic individuals, and their predictive role in non-insulin dependent diabetes mellitus, has been documented in various ethnic groups, suggesting a two-step process in the natural history of the disease, i.e. ''compensated'' insulin resistance followed by failure of insulin secretory response leading to a hyperglycaemic (diabetic) phase. In Caucasians at least, in whom the insulin-resistance syndrome includes clear abnormalities in its most potentially atherogenic elements, this natural history suggests that the cardiovascular complications associated with non-insulin dependent diabetes mellitus originate from the initial ''pre-diabetic'' phase of the disease. Early prevention would theoretically require intervention before hyperglycaemia occurs (or even ii it will never occur) for all upper body obese subjects who present with insulin-resistance syndrome.