Divergent correlations of circulating dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding.

We evaluated the insulin response to a standard oral glucose tolerance test (OGTT) and in vitro insulin binding to erythrocytes (RBC) in 26 women from 3 groups: Group NW, normal women (n = 11); Group DS, women (n = 9) with elevated serum DHEAS concentrations, greater than 400 micrograms/dl (greater than 10.84 mumol/L); and Group IR, women (n = 6) with elevated basal plasma insulin concentrations (IRI). There was a significant linear correlation between the area under the insulin response curve (IRI-AUC) and serum testosterone (T) (r = 0.78, p = 0.0001). Using stepwise multiple linear regression, IRI-AUC was characterized as a function of both serum T and DHEAS; positively with T and negatively with DHEAS. In vitro (n = 17), there was a positive correlation between RBC-insulin binding and serum DHEAS (r = 0.54, p = 0.029) and a negative correlation between RBC-binding and T (r = -0.57, p = 0.017). We conclude that DHEAS may enhance insulin binding and action and that DHEAS and T have divergent functional relationships with IRI. DHEAS and T may therefore exert opposing effects on insulin secretion and action.