The Interplay of Type 2 Diabetes Status, Cardiorespiratory Fitness Level, and Sudden Cardiac Death: A Prospective Cohort Study

Background: To evaluate the individual and joint effects of type 2 diabetes (T2D) status and cardiorespiratory fitness (CRF) level with sudden cardiac death (SCD) risk. Methods: Prevalent T2D was defined based on guideline recommendations, and CRF level was assessed using a respiratory gas-exchange analyzer during exercise testing at baseline, in 2308 men aged 42-61 years. T2D status was classified as either “Yes” or “No,” and CRF level was classified as low, medium, or high. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for SCD. Results: A total of 264 SCDs occurred during a median follow-up of 28.1 years. Comparing Yes vs No history of T2D, the multivariable-adjusted HR (95% CI) for SCD was 1.79 (1.19-2.72). Comparing low vs high CRF levels, the corresponding adjusted HR (95% CI) for SCD was 1.77 (1.21-2.58). The HRs persisted when T2D status was further adjusted for CRF level, and vice versa. Compared with No-T2D & medium-high CRF level, men with No-T2D & low CRF and those with Yes-T2D & low CRF had an increased SCD risk: (HR = 1.87, 95% CI, 1.38-2.55) and (HR = 3.34, 95% CI, 2.00-5.57), respectively. No significant association occurred between men with Yes-T2D & medium-high CRF and SCD risk (HR = 1.46, 95% CI, 0.46-4.65). Modest evidence indicated the presence of additive and multiplicative interactions between T2D status and CRF level, in relation to SCD. Conclusions: An interplay exists between T2D status, CRF level, and SCD risk in middle-aged and older men. Higher CRF levels may mitigate the increased SCD risk observed in men with T2D.