Decreased hepatic insulin extraction in upper body obesity: relationship to unbound androgens and sex hormone binding globulin

Abstract

Hyperinsulinemia is a well-recognized entity of simple obesity. It is demonstrated that hyperinsulinemia is associated with upper body fat and fat cell hypertrophy. Androgen excess and lower levels of sex hormone binding globulin (SHBG) may produce fat cell hypertrophy and hyperinsulinemia as well. We measured serum insulin and C-peptide levels during an OGTT in two groups of obese premenopausal women to determine whether the hyperinsulinemia is due to hypersecretion or due to a diminished hepatic extraction of insulin. In this study, we found no correlation between the insulin and C-peptide levels or their ratio and the degree of obesity. However, a significant correlation was found between the waist-to-hip circumference ratio (WHR), used as an index of body fat distribution, and the areas of insulin ( r = 0.55; P < 0.001) and C-peptide ( r = 0.51; P < 0.001). SHBG and free androgen index (FAI) were also significantly related to these areas. The peripheral C-peptide/insulin molar ratio has been assumed to reflect changes in hepatic insulin extraction while the corrected C-peptide response reflects β-cell function. WHR was negatively related to this ratio ( r = −0.44; P < 0.005) and SHBG showed a positive correlation ( r = 0.34; P < 0.05). Stepwise multiple regression analysis revealed that the 2-h insulin and C-peptide values and both curve areas can be explained up to 40–80% by sex hormones and anthropometric variables. Also the C-peptide/insulin molar ratio is dependent in a first step on WHR ( r 2 = 0.23; P < 0.01). Using the corrected C-peptide response, no differences were found in glucose induced insulin secretion between both types of obesity; this finding however, does not exclude the possibility of some increased β-cell secretion in abdominal obesity. From the results of this study, we can conclude that a diminished hepatic insulin extraction, contributes to an important extent to the hyperinsulinemia in abdominal obesity.