Association between insulin-like growth factor-I:insulin-like growth factor-binding protein-1 ratio and metabolic and anthropometric factors in men and women

Several prospective observational studies have suggested that elevated circulating IGF-I levels are associated with an increased risk of cancer. These observations may provide a potential mechanism through which previously identified metabolic and anthropometric factors., such as obesity and elevated insulin and glucose levels, may operate. We therefore examined metabolic and anthropometric influences on circulating levels of insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-1 (IGFBP-1), and the IGF-I:IGFBP-1 ratio in a middle-aged population of 349 men and 492 women. IGF-I showed only modest inverse associations with indices of adiposity. However, we found that low IGFBP-I levels and an increased IGF-I:IGFBP-1 ratio were strongly associated with increased levels of insulin and glucose in men and women. Body mass index was also positively related to the IGF-I:IGFBP-1 ratio in men (P < 0.001) and women (P < 0.001), independent of metabolic correlates of IGFBP- 1 and IGF-I. Similarly, waist:hip ratio and waist circumference were also associated with an increased IGF-I:IGFBP-1 ratio and low circulating IGFBP-1 levels. These findings suggest that individuals with greater fat mass and upper body obesity may have elevated levels of bioavailable or free IGF-I, which could, in part, mediate the reported associations among metabolic and anthropometric factors and cancer risk.