Clinical Endocrinology (1990), 33,415422
DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP-1) IN EXTREME OBESITY J . U . WEAVER, J. M . P. HOLLY, P. G . KOPELMAN, K. N O O N A N , C . G . G I A D O M , N. WHITE, S. VIRDEE AND J. A. H . WASS Medical Unit and Department of Chemical Pathology, The London Hospital; Endocrine Department, Chelsea Hospital for Women, London S W3 and Department of Endocrinology and Chemical Endocrinology, St Bartholomew’s Hospital, London, E C l A 7BE, U K (Received 9 January 1990; returned,for revision I3 February 1990; .finally revised 10 April 1990: accepred 2 May I990)
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-I). 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-I and fat distribution in 25 extremely obese, menstruating women (mean weight 107 f3 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 fSEM; 21 + 2 pmol/l), a normal IGF-I, but reduced IGFBP-I (14.6f2 pg/l); in I5 women IGFBP-I levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24f2 nmol/l) but total testosterone values (1.9 f0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio ( P < 0.01, r2=0.306) and inversely correlated with SHBG ( P < 0.01, r2=0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio ( P < 0.001, r2 =0.383). No correlation was found between IGFBP-I 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 Correspondence: Dr P. G. Kopelman, Medical Unit, The London Hospital, Whitechapel, London El IBB,
UK.
415
416
J . U . Weaver et al. levels (P
DECREASED SEX HORMONE BINDING GLOBULIN (SHBG) AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP-1) IN EXTREME OBESITY J . U . WEAVER, J. M . P. HOLLY, P. G . KOPELMAN, K. N O O N A N , C . G . G I A D O M , N. WHITE, S. VIRDEE AND J. A. H . WASS Medical Unit and Department of Chemical Pathology, The London Hospital; Endocrine Department, Chelsea Hospital for Women, London S W3 and Department of Endocrinology and Chemical Endocrinology, St Bartholomew’s Hospital, London, E C l A 7BE, U K (Received 9 January 1990; returned,for revision I3 February 1990; .finally revised 10 April 1990: accepred 2 May I990)
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-I). 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-I and fat distribution in 25 extremely obese, menstruating women (mean weight 107 f3 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 fSEM; 21 + 2 pmol/l), a normal IGF-I, but reduced IGFBP-I (14.6f2 pg/l); in I5 women IGFBP-I levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24f2 nmol/l) but total testosterone values (1.9 f0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio ( P < 0.01, r2=0.306) and inversely correlated with SHBG ( P < 0.01, r2=0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio ( P < 0.001, r2 =0.383). No correlation was found between IGFBP-I 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 Correspondence: Dr P. G. Kopelman, Medical Unit, The London Hospital, Whitechapel, London El IBB,
UK.
415
416
J . U . Weaver et al. levels (P
