Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women

Objective: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-li ke growth factor binding protein 1 (IGFBP-1), and disturbances in the growt h hormone-IGF-I axis are linked to obesity and cardiovascular diseases. How ever, whether the association between leptin and the GH-IGF-I axis is alter ed with increasing obesity is not known. We therefore examined the relation ship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and wome n with or without obesity in a population study. Design and subjects: Healthy subjects (n = 158; 85 men and 73 pre- and post menopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cro ss-sectional design. Methods: Anthropometric measurements (body mass index (BMI) and waist circu mference) and oral glucose tolerance tests were performed. Radioimmunoassay s were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for s pecific insulin and proinsulin. Results: Leptin inversely correlated to IGFBP-1 in non-obese men (P < 0.05) and obese postmenopausal women (P < 0.05). In contrast, leptin did not cor relate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P < 0.01) and non-obese premenopausal women (P < 0.05). T he association between leptin and IGFBP-1 was lost after adjustment for ins ulin. In multivariate analyses taking measures of adiposity into account, l ow proinsulin, and IGF-I in combination with old age, but not leptin, predi cted high IGFBP-1 levels. Conclusions: Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated wit h IGFBP-1 in non-obese men and premenopausal women. However, these associat ions were lost with increasing central obesity in men and premenopausal wom en and after control for insulin. Therefore, this study suggests (i) that l eptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationshi p between leptin, IGFBP-1 and insulin.