Diabetes
Insulin-like growth factor-1, lean mass and fat mass in type 2 diabetes prevention: Mendelian randomization study in East Asian populations KWOK Man Ki* Man Ki KWOK Parco Ming Fai SIU C Mary SCHOOLING
Background: Differences in body composition by ethnicity and gender have been implicated in susceptibility to type 2 diabetes mellitus (T2DM). However, few sex-specific assessments of body composition and its biological drivers, insulin-like growth factor-1 (IGF-1), on T2DM have been conducted. This study assessed the role of IGF-1 in T2DM, and examined whether any mediation by lean mass and/or fat mass, in men and women in East Asian settings.
Methods: In a two-sample Mendelian randomization (MR) study, genetic variants predicting IGF-1 and body composition (fat mass or lean mass) were obtained from young Chinese (aged ~17.6 years) from the Hong Kong “Children of 1997” Biobank (n=3,443). Genetic associations with T2DM in men and women of East Asian descent (aged 60.8 years for cases and 55.8 years for controls) were from the largest available East Asian GWAS (n=433,540). Univariable and multivariable MR were used to obtain total and direct effects of IGF-1 and fat mass or lean mass on T2DM. Mediation analyses were conducted to obtain the indirect effects (via the mediator) using the product method.
Results: Genetically predicted higher IGF-1 was associated with a higher risk of T2DM in both sexes [odds ratio (OR) 1.06 per 1 standard deviation (SD) of IGF-1, 95% confidence interval (CI): 1.01 to 1.12]. Fat and lean mass were unrelated to T2DM. Genetically predicted IGF-1 was associated with more lean mass (in men), but not fat mass. After allowing for lean mass or fat mass, IGF-1 was no longer associated with T2DM. No indirect effects of lean mass or fat mass were found for the associations of IGF-1 with T2DM were found.
Conclusions: IGF-1 directly affected T2DM, independent of body composition, in both men and women. Neither fat mass nor lean mass was related to T2DM risk, consistent with a higher T2DM risk despite a lower prevalence of obesity among East Asians.