Approved Research

Potential drivers, mediating pathways, and consequences of IGF-1 using Mendelian randomization: Roles of insulin-like growth factor 1 (IGF-1), lean mass and fat mass in type 2 diabetes mellitus

Lay summary

Major chronic diseases inexorably poses a high societal burden globally. More effective prevention is urgently needed. Observed ethnic and gender differences in major chronic diseases implies that optimal intervention strategies may vary by ethnicity and gender. From an evolutionary biology perspective, insulin-like growth factor (IGF)-1 and its downstream factors may generate various disease patterns by gender and ethnicity. The purposes of this study are to examine whether IGF-1 is associated with major chronic diseases in men and women, and if so, to identify potential drivers of IGF-1, and to elucidate mediating pathways from IGF-1 to chronic diseases. As an exemplar of the importance of sex-specific research in IGF-1 and chronic diseases, specifically this study will (i) assess the causal role of IGF-1 in type 2 diabetes mellitus (T2DM) in men, women, and both sexes; and (ii) examine whether the effect of IGF-1 on T2DM is fully or partially mediated via lean mass and/or fat mass in men, women, and both sexes. The study will make use of Mendelian Randomization (MR). MR is a research method that uses genetic variation to investigate the causal relationships of exposures with health outcomes, which can overcome the major limitations of observational studies. The evidence generated from this study using the UK Biobank will contribute to the development of more targeted dietary and physical activity recommendations and pharmaceutical interventions by gender and ethnicity.