Epidemiological and clinical data suggest a relationship between
hyperinsulinism and macroangiopathy in non
insulin-dependent diabetes. On the other hand, a relationship between the plasma free
insulin level and macroangiopathy has not been documented in
insulin-dependent diabetes. Other abnormalities in addition to
hyperinsulinism and
glucose intolerance are frequently associated in the presence of
insulin resistance and have been grouped by Reaven under the term syndrome X: raised VLDL
triglycerides, decreased HDL, and raised blood pressure. Iatrogenic
hyperinsulinism appears to be an arterial risk factor, but by what mechanism may it also constitute an independent risk factor? The following theoretical aspects of a possible atherogenic role of
hyperinsulinism are currently being investigated: a)
insulin stimulates the proliferation and migration of smooth muscle cells either directly or via a rise in IGF1;
b) insulin induces lipogenesis in the intima-media, but it has not been demonstrated that this in situ lipogenesis is atherogenic; c)
insulin raises the VLDL production, decreases HDL and modifies the clearance of
LDL; d)
insulin increases blood pressure by stimulating both the renal reabsorption of
sodium and the sympathetic nervous system;
insulin resistance may also be expressed at the level of the Na-K-
ATPase of vascular smooth muscle cells by decreasing the
vasodilator effect of the
hormone; e) lastly,
insulin induces a defect of fibrinolysis mediated by an increase in the level of
plasminogen activator inhibitors (PAI1). In conclusion, the combination of
hyperglycemia and
hyperinsulinism is probably damaging to the artery. Therapeutic intervention studies are necessary to confirm and define the role of
hyperinsulinism in macroangiopathy and to answer the unresolved questions: direct or indirect role? effect of endogenous and/or
exogenous hyperinsulinism?