Introduction: Obesity and poor cardiorespiratory fitness (CRF) commonly coexists in type 2 diabetes (T2DM). Moreover, CRF has been associated with lower mortality risk in T2DM patients. In this study, we assessed the modulatory impact of fitness on mortality risk in T2DM patients across the obesity spectrum.

Methods: We identified 6,888 T2DM patients (age 58.3+10.1 years) with no evidence of ischemia as indicated by a maximal standardized exercise treadmill test. We established two CRF categories based on age-adjusted median peak metabolic equivalents (METs) achieved: Unfit (5.4±1.3 METs; n=3,474) and Fit (9.0±2.3 METs; n=3414). We also defined the cohort based on body mass index (BMI) normal-weight (BMI 18.5-24.9 kg/m2); over-weight (BMI 25.0-29.9 kg/m2); and obese (BMI ≥30 kg/m2). We then combined the BMI and CRF categories to form a total of six groups CRF-BMI categories. Cox proportional hazards models, adjusted for known risk factors were constructed to assess the association between CRF-BMI interaction and mortality risk.

Results: During a follow-up of 14.2+6.9 years, 2,495 patients died, accounting for 25.5 events/1,000 person-years of observation. When CRF-BMI groups were considered, the normal-weight-Fit category was used as the referent. Mortality risk in the normal-weight but Unfit patients was 64% higher compared to their Fit counterparts (HR 1.64; 95% CI: 1.35-2.00). In the overweight category, mortality risk was 20% lower in the Fit (HR 0.80; 95% CI: 0.67-0.94) and 28% higher (HR 1.28; 95% CI: 1.09-1.51) in Unfit patients. In obese category the risk was 29% lower for the Fit (HR 0.71; 95% CI: 0.60-0.86) and 23% higher for the Unfit patients (HR 1.23; 95% CI: 1.05-1.45).

Conclusion: Increased CRF favorably modulates mortality risk across the obesity spectrum in T2DM patients. Poor fitness had a substantially greater and negative impact on Normal than over-weight and obese individuals.


E. Nylen: None. P. Kokkinos: None. C. Faselis: None. P. Narayan: Research Support; Self; AstraZeneca, Eli Lilly and Company. P. Karasik: None. J.N. Myers: None.

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