AB Purpose: Fitness decline, high body mass index (BMI), and insulin resistance (IR) are associated with worsening cardiometabolic risk factors prospectively; modification of the fitness change effect by BMI and IR remains unknown. Methods: Participants from the Coronary Artery Risk Development in Young Adults study without diabetes at year 0 (Y0) (n = 2048, 43.4% men; mean age, 25 yr) had fitness quantified by treadmill at Y0 and Y20. Y0 BMI was normal (nBMI <25 kg[middle dot]m-2) or high (hBMI >=25 kg[middle dot]m-2). Y0 IR status was insulin sensitive (IS) (homeostatic model assessment IR <1.84 (75th percentile)) or insulin resistant (IR) (homeostatic model assessment IR >=1.84). Four groups were established: nBMI/IS, hBMI/IS, nBMI/IR, and hBMI/IR. Y0 fitness was low (<33rd percentile for sex) or average high (>=33rd percentile for sex). Fitness change (treadmill time: Y20-Y0) was maintained (increase or decline <=20th percentile for sex) or decreased (decline >20th percentile for sex). The outcomes were incident diabetes and percentage change over 25 yr in weight, waist girth, blood pressure, and lipid profile. Analysis was by multiple linear regression and proportional hazards regression with adjustment for individual characteristics. Results: Maintained fitness after 20 yr was associated with greater increase in HDL cholesterol and less increase in weight, waist girth, blood pressure, and triglycerides than decreased fitness, similarly for the groups defined by BMI and IR. Maintained fitness reduced the rate of incident diabetes in IS but not IR participants. Conclusions: Maintained fitness after 20 yr was associated with more favorable middle-age cardiometabolic risk factors than decreased fitness; this benefit might be blunted by baseline IR.
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