Regional fat distribution--implications for type II diabetes

Abdominal obesity is closely associated with risk factors for cardiocerebrovascular disease and NIDDM and the precipitation of these diseases. Together, they seem to constitute a metabolic syndrome where hyperinsulinaemia, insulin resistance, hyperlipidaemia, hypertension, visceral fat accumulation, cardiocerebrovascular disease and NIDDM are the individual constituents. The background to this syndrome might be a primary aberration expressing itself as an increased sensitivity of the hypothalamo-adrenal axis, and subsequent inhibition of sex steroid hormone secretions. This in turn will probably be followed by metabolic derangements, primarily peripheral insulin resistance, as well as by visceral fat accumulation by mechanisms which are partially visualized by recent work in the field. Visceral fat accumulation may then amplify the metabolic aberrations via hepatic effects of excessive concentrations of portal FFA, producing hyperproteinaemia, hyperglycaemia, hyperinsulinaemia and, perhaps, hypertension. The background to the central endocrine aberration remains more speculative, but factors leading to increased cortisol production, including specific stress reactions, tobacco smoking and alcohol may turn out to be important. The tentative conclusion provides a hypothesis for further work, and has recently obtained considerable support from further observations in humans in other than the endocrine and metabolic areas, as well as from studies in experimental animal models, where such factors can be studied under fully controlled conditions, which is not possible in humans for ethical reasons.