DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN‐LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP‐1) IN EXTREME OBESITY

SUMMARY Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in‐vitro and in‐vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin‐like growth factor small binding protein (IGFBP‐1). IGFBP‐1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF‐1, IGFBP‐1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 |Mp 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean |Mp SEM; 21 |Mp 2 μmo1/1), a normal IGF‐1, but reduced IGFBP‐1 (14.6 |Mp 2, μg/1); in 15 women IGFBP‐1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24|Mp2 nmol/1) but total testosterone values (1.9 |Mp 0.1 nmo1/1) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/I‐1 ratio (P < 0.01, r 2 =0.306) and inversely correlated with SHBG (P <0.01, r 2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P < 0.001, r 2 = 0.383). No correlation was found between IGFBP‐1 and W/H ratio but a strong positive correlation was seen between IGFBP‐1 and SHBG (P < 0.001, r 2 =0.466). Furthermore, an equally significant inverse correlation was found between IGFBP‐1 and insulin levels (P <0.001, r 2 =0.474). Testosterone and fasting IGF‐1 did not show any correlation with the studied variables. Multivariate analysis suggested that insulin was the strongest factor involved in the regulation of IGFBP‐1 levels, whereas the level of SHBG was primarily determined by IGFBP‐1 concentration and W/H ratio. We conclude that reduced SHBG and IGFBP‐1 found in extreme obesity are inversely correlated to the prevailing hyperinsulinaemia and to increasing upper segment obesity. These findings provide further evidence to support the hypothesis for insulin being an important regulator of both binding proteins, SHBG and IGFBP‐1.