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Sex-specific associations of adiposity with cardiometabolic traits: multi-life-stage cohort study with repeat metabolomics

Background: Sex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different cardiometabolic consequences of adiposity in females and males. We examined whether adiposity influences cardiometabolic trait levels differently in females and males at four different life stages. Methods: Data were from two generations (offspring, Generation 1 [G1] and their parents, Generation 0 [G0]) of the Avon Longitudinal Study of Parents and Children birth cohort study. Body mass index (BMI) and total fat mass from dual-energy x-ray absorptiometry were measured at mean age 9y, 15y and 18y in G1. Waist circumference was measured at 9y and 15y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15y, 18y and 25y in G1. In G0, all three adiposity measures and the same 148 traits were available at 50y.Using linear regression models, sex-specific associations of adiposity measures at each time point (9y, 15y and 18y) with cardiometabolic traits 3 to 6 years later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50y. Results: 3081 G1 and 4887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males at younger ages (15y-25y) and associations were more similar between the sexes or stronger in females at 50y, particularly for apolipoprotein-B-containing lipoprotein particles and lipid concentrations. For example, a 1-SD (3.8 kg/m2) higher BMI at 18y was associated with 0.36 SD (95% Confidence Interval (CI) = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females. In contrast, at 50y, a 1-SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females respectively. Sex-specific associations of DXA-measured fat mass and waist circumference were similar to findings for BMI in both generations and at all ages. Conclusion: The results of this study suggest that the adverse cardiometabolic effects of adiposity are stronger and begin earlier in the life course among males compared with females until mid life, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.