Independent and joint association of fat‐to‐muscle mass ratio and cardiorespiratory fitness with type 2 diabetes mellitus incidence: A prospective cohort study

AIM: Body mass index (BMI) might fail to distinguish between fat and muscle mass. The fat-to-muscle mass ratio (FMR) and cardiorespiratory fitness (CRF) may provide complementary insights into the risk of type 2 diabetes mellitus (T2DM). This study aimed to investigate the independent and joint associations of FMR and CRF with incident T2DM. METHODS: This prospective analysis included 60 837 adults from the UK Biobank without diabetes at baseline. FMR was assessed via bioelectrical impedance analysis, and CRF was estimated from a submaximal cycle test. Cox proportional hazards models evaluated associations with T2DM incidence. Additive and multiplicative interaction effects were further estimated. Predictive performance was evaluated using time-dependent ROC analysis. RESULTS: Over a median 14.49-year follow-up, 2439 participants developed T2DM. Higher FMR (per 1-SD) was independently associated with higher T2DM risk in women (HR = 1.17, 95%CI: 1.07-1.27) and men (HR = 1.32, 95%CI: 1.23-1.42). Higher CRF (per 1-MET increment) was associated with lower risk in women (HR = 0.84, 95%CI: 0.80-0.89) and men (HR = 0.82, 95%CI: 0.79-0.86). Participants with both high FMR and low CRF had the highest risk (HR = 1.81, 95%CI: 1.59-2.07). This association was strongest in adults <60 years. Adding FMR and CRF to the Cambridge Diabetes Risk Score significantly improved predictive accuracy at 3, 5 and 10 years. CONCLUSION: FMR and CRF were independent predictors of T2DM, with their combination identifying the highest-risk phenotype. Integrating FMR and CRF assessment enhances T2DM risk stratification and identifies high-risk individuals who may benefit from lifestyle interventions focusing on improving body composition and fitness.