Cardiorespiratory Fitness is Inversely Associated with Diabetes and Nonfatal CVD in Men with Metabolic Syndrome

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The primary clinical outcomes of metabolic syndrome (Metsyn) are cardiovascular disease (CVD) and diabetes mellitus (DM). Cardiorespiratory fitness (CRF) is inversely associated with CVD mortality in men with Metsyn. Whether higher CRF protects against DM and nonfatal CVD events in individuals with Metsyn is unknown. PURPOSE: We examined the prospective association of CRF with incident DM and nonfatal CVD in 4031 men (mean±SD, age = 47±9 years; body mass index (BMI) = 29±4 kg/m2) who completed a medical examination at the Cooper Clinic between 1979–2002. METHODS: At baseline, participants were free of physician diagnosed DM and CVD (myocardial infarction and stroke), had fasting plasma glucose <126 mg/dL, were not taking insulin, and had measured clinical variables that met ATP-III criteria for Metsyn. CRF was denned as thirds of maximal treadmill exercise duration. DM and nonfatal CVD cases were ascertained from mail-back questionnaires administered between 1982 and 2004. We used Cox regression analysis to examine the association between CRF and the study outcomes. RESULTS: During an average follow-up of 8.9±6.1 years, there were 239 (5.9%) cases of DM and 184 (4.6%) cases of CVD. Across incremental thirds of CRF, the age-and examination year adjusted rates (per 10,000 man-years) of DM were 110.0, 67.1, and 35.2; and of CVD were 72.0, 44.6, and 41.8 (linear trend P <0.001 each). After adjusting for age, examination year, smoking, alcohol intake, and family history of DM and CVD, hazard ratios (95% CI) for DM were 1.00 (referent), 0.63 (0.46–0.85), and 0.33 (0.24–0.47), linear trend P <0.001; and for CVD were 1.00 (referent), 0.59(0.41–0.86), and 0.55 (0.39–0.82), linear trend P <0.01. These patterns of association were materially unchanged after further adjustment for abnormal exercise electrocardiogram responses, and baseline risk factor levels, including fasting glucose and BMI. CONCLUSION: CRF is inversely and independently associated with the incidence of DM and nonfatal CVD events in men at high-risk for these outcomes based on the presence of Metsyn. These findings underscore the importance of promoting higher CRF, presumably through greater physical activity, in the management of Metsyn and in the prevention of DM and CVD.