Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations (Sweden)

Objective: In this study we test the hypothesis of a nonlinear relationship of IGF-I with indices of body fat such as body mass index (BMI), insulin, and leptin. Methods: The controls used in three case-control cancer studies nested in the Northern Sweden Health and Disease Cohort, were combined for this analysis. Measurements of plasma IGF-I, IGFBP-3, insulin, and leptin were available for 445 men and 391 women. Results: In both men and women we found the highest mean IGF-I levels in subjects with BMI between 24 and 26. IGF-I concentrations decreased toward BMI less than or equal to 20 and BMI > 30 in men; however, the results for women did not reach statistical significance. The molar ratio of IGF-I/IGFBP-3 showed a similar profile to that of IGF-I, although much less pronounced. The observed peak mean IGF-I levels in the second quintiles of insulin and leptin in men supported these findings. No significant variation of mean IGF-I levels across quintiles of insulin and leptin were observed in women. Conclusions: The results of this study provide evidence that IGF-I plasma concentrations vary substantially over a wide range of body weight and that the relationship is nonlinear.