The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: Evidence from the ProtecT (Prostate testing for cancer and Treatment) study

Objective: Adiposity is positively associated with advanced, metastatic, and fatal prostate cancer. Obesity-related variations in insulin-like growth factors (IGF-I and-II) and their binding proteins (IGFBPs) could underlie these associations. Methods: We investigated associations of adiposity throughout the life course (determined retrospectively) with serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in a population-based study of 1,106 healthy men. Results: IGF-I and IGF-II showed inverted U-shaped associations with adult body mass index (BMI) (p quadratic model = 0.04 and 0.06, respectively), although differences between quartiles with the highest and lowest IGF-I levels were small (no more than 5 ng/ml). IGFBP-2 was strongly inversely related to adult BMI (-22% change per SD increase in BMI; 95% confidence interval (CI)-24% to-19%) and waist circumference (-18% change per SD increase in waist circumference; 95% CI-20% to-15%) (p < 0.001). IGFBP-3 was positively related to BMI (63.5 ng/ml increase per SD increase in BMI; 95% CI-2.69 to 129.8, p = 0.06). IGFBP-2 and IGFBP-3 were strongly related to body shape change from childhood to adulthood, with men who gained the most weight having the lowest IGFBP-2 (9% lower per category body shape change; 95% CI-11% to-7%, p < 0.001) and the highest IGFBP-3 (50 ng/ml increase per category; 95% CI 8 to 92, p = 0.02). Conclusions: We provide evidence that adiposity and change in body shape through the life course are related to the IGF system, with the largest effect of adiposity being to lower IGFBP-2, a possible marker of insulin resistance. The results suggest that circulating IGF-I levels may not be important mediators of the association of adiposity with aggressive prostate cancer, but the role of IGFBP-2 deserves further investigation.