Muscle Strength, Genetic Risk, and Type 2 Diabetes Among Individuals of South Asian Ancestry: A UK Biobank Study

Objective To examine the independent and combined associations of genetic risk and muscle strength with the risk of incident type 2 diabetes (T2D) and glycated hemoglobin (HbA1c) among individuals of South Asian ancestry. Design and Methods This study included 5288 South Asian individuals (mean age 52.5 years; 52.3% men) from the UK Biobank study. Baseline assessments were conducted between 2006 and 2010. Muscle strength was assessed through a hand dynamometer and expressed relative to fat-free mass. Sex-and age-specific tertiles were used to classify muscle strength into three categories. Genetic risk of T2D was quantified using a weighted polygenic risk score calculated from 22 distinct South Asian-specific single nucleotide polymorphisms for T2D. Results Compared to the bottom tertile of genetic risk for T2D, the highest had increased odds of incident T2D (odds ratio: 1.62; 95% confidence interval [CI]: 1.31-2.00) and HbA1c levels (beta: 0.80; 95% CI 0.41-1.19). Compared to high muscle strength, low muscle strength was associated with 89% higher odds of incident T2D (odds ratio: 1.89; 95% CI 1.52-2.35) and higher HbA1c levels (beta: 0.95; 95% CI 0.55-1.35), after adjustment for confounders and genetic susceptibility to T2D. Joint analyses revealed lower muscle strength was consistently associated with higher odds of incident T2D and HbA1c levels across all genetic risk strata. Conclusion Polygenic risk scores for T2D could have great prognostic value in preemptively identifying individuals of South Asian ancestry at high genetic risk of T2D. Regardless of T2D genetic risk, greater muscle strength is linked to lower T2D risk and HbA1c levels.