Cardiorespiratory Fitness and Risk of Microvascular Complications in Patients with Type 2 Diabetes Mellitus

This study investigated the association between cardiorespiratory fitness (CRF) and the risk of incident microvascular complications in patients with type 2 diabetes mellitus (T2DM), as well as the effects of genetic risk and potential mediation by circulating biomarkers.

This prospective analysis included 3,102 adults with T2DM from the UK Biobank. CRF was estimated as maximal oxygen uptake using a submaximal cycle test and categorized as low, moderate, or high. Cox proportional hazards models estimated hazard ratios (HRs) for incident diabetic nephropathy, retinopathy, and neuropathy. Interactions with a polygenic risk score and mediating roles of biomarkers were evaluated.

Over a median follow-up of 12.47-years, 331 nephropathy, 268 retinopathy, and 88 neuropathy cases were recorded. Compared to low CRF, moderate and high CRF were associated with a 22% (HR, 0.78; 95% confidence interval [CI], 0.61 to 0.99) and 45% (HR, 0.55; 95% CI, 0.36 to 0.85) lower risk of nephropathy, respectively. Each 1-metabolic equivalent of task increment in CRF was linked to 11% lower nephropathy risk. No significant associations were found for retinopathy or neuropathy. Genetic predisposition did not modify the association between CRF and diabetic nephropathy. Triglycerides and white blood cell count accounted for 7.46% and 12.88% of the association, respectively.

Higher CRF is independently associated with a lower risk of diabetic nephropathy in T2DM, and genetic risk does not alter this relationship. The association is partially mediated by triglycerides and white blood cell count. Assessing CRF may improve risk stratification and prevention of diabetic kidney disease.