Associations of increased physical performance and change in body composition with molecular pathways of heart disease and diabetes risk.

Higher physical activity is associated with a reduced hazard for a plethora of diseases. It has remained unknown how the two primary physical activity-associated health effects, improved physical performance and change in body composition, independently modulate metabolic profiles toward a reduced risk for adverse outcomes. Here, we utilized a prospective cohort of 664 young men undergoing military service. We studied the metabolic associations of changes in muscle performance and body composition during military service (range 6-12 mo). We subsequently replicated our results for body composition change in 234 population-based samples with a 7-yr follow-up. We found that increased physical performance was associated with reduced very-low-density lipoprotein (VLDL)-related measures [change in VLDL cholesterol: beta = -0.135; 95% confidence interval (CI) = -0.217, -0.054, P = 1.2 × 10-3] and lower inflammation (change in glycoprotein acetyls: beta = -0.138, 95% CI = -0.217, -0.059, P = 6.5 × 10-4), independent of change in body composition. Lower body fat percentage, independent of change in muscle performance, was associated with metabolic changes including lower low-density lipoprotein (LDL) cholesterol measures (change in LDL cholesterol: beta = -0.193, 95% CI = -0.295, -0.090; P = 2.5 × 10-4), increased high-density lipoprotein (HDL) cholesterol measures (change in large HDL cholesterol: beta = 0.316, 95% CI = 0.205, 0.427; P = 3.7 × 10-8), and decreased concentrations of amino acids (change in leucine concentration: beta = -0.236, 95% CI = -0.341, -0.132; P = 1.0 × 10-5) that are type 2 diabetes biomarkers. Importantly, all body fat percentage associations were replicated in a general population-based cohort. Our findings indicate that improved muscle performance showed weaker associations on the metabolic profiles than change in body composition and reduction in body fat percentage reduces cardiometabolic risk mediated by atherogenic lipoprotein particles and branched-chain and aromatic amino acid concentrations.