Dehydroepiandrosterone: the "missing link" between hyperinsulinemia and atherosclerosis?

A well-established epidemiologic association exists between hyperinsulinemia and macrovascular disease. However, the mechanism or mechanisms by which hyperinsulinemia promotes atherogenesis is unknown. Recent evidence indicates that the adrenal steroid dehydroepiandrosterone (DHEA) exerts multiple antiatherogenic effects and also suggests that hyperinsulinemia may reduce serum DHEA and DHEA-sulfate levels by decreasing production and enhancing metabolic clearance. We advance the hypothesis that hyperinsulinemia promotes macrovascular disease in part by reducing serum DHEA and DHEA-sulfate levels and illustrate how this may be the case in two clinical conditions characterized by hyperinsulinemic insulin resistance: aging and obesity.