LOW-LEVELS OF SEX HORMONE-BINDING GLOBULIN AND HYPERPROINSULINEMIA ASMARKERS OF INCREASED PANCREATIC BETA-CELL DEMAND IN MEN

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the p resence of an increased pancreatic beta-cell demand (e.g. obesity) bot h absolute and relative increases in proinsulin secretion occur. In th e present study we investigated the correlation between SHBG and pancr eatic beta-cell secretion in men with different body compositions. Eig hteen young men (30.0 +/- 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m(2) were submit ted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly cor related with baseline insulin (r = -0.58, P<0.05), proinsulin (r = -0. 47, P<0.05), C-peptide (r = -0.55, P<0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P<0.05). Stepwise regression a nalysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P<0.05). When subjects were divided into obese (BMI >28 kg/m(2), N = 8) and nonobese (BMI less than or equal t o 25 kg/m(2), N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin leve ls. For the first time using a specific assay for insulin determinatio n, a strong inverse correlation between insulinemia and SHBG levels wa s confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic beta-cell secretion, mainly for the 120-min pos t-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic beta-cell demand .