Abstract P250: Sex-Related Differences in the Associations of Variability in Body Mass Index and Metabolic Health With Incidence of Obesity and Metabolically Unhealthy Status: The Framingham Offspring Study

Abstract

Introduction: Higher variability of body mass index (BMI) is associated with both cardiometabolic and cardiovascular disease in high-risk individuals. It is unclear, however if variability of BMI impacts metabolic health or obesity risk in healthy adults and if any potential associations vary for women vs. men. Methods: We classified Framingham Offspring cohort participants (n=3,961, mean age 50.8 years, 53.8% women) according to their obesity (BMI ≥30 kg/m 2 ) and metabolic health status (<2 non-obesity NCEP ATPIII conditions) and followed them prospectively 1987 to 2014. BMI and metabolic syndrome (MetS)-associated measures in the top quintile of the variance independent of the mean were classified as being variable. ‘Variable metabolic health’ (VMH) was defined as ≥2 ‘variable’ non-obesity MetS components. We estimated sex-specific incident rate ratios (IRRs) and 95% confidence intervals (95% CIs) for the associations of time-varying obesity, metabolic health status, and variability of BMI and metabolic health with the incidence of obesity and metabolically unhealthy state using Cox proportional hazards regression for interval-censored outcomes with age as the time scale. Results: On follow-up, 567 participants (313 women) developed new-onset obesity over 9,434 person-periods, and 759 individuals (437 women) developed a metabolically unhealthy state over 5,754 person-periods). After adjustment for covariates, being metabolically unhealthy was associated with a greater risk of new-onset obesity among women (153%, 95% CI 96-229%) compared with men (33%, 95% CI: 1, 79%; p sex- difference =0.005). Similarly, BMI variability was associated with a higher risk of becoming metabolically unhealthy in women (134%, 95% CI: 76, 212%) compared with men (-11%, 95% CI: -49, 53% (p sex-difference =0.0007). Among participants without obesity, BMI variability was associated with a greater risk of incident obesity in women (275%, 95% CI: 185, 393%) compared with men (33%, 95% CI: -22, 129% p sex- difference =0.005). Obesity was positively associated with greater risk of incident unhealthy metabolic state in women (157%, 95% CI: 93, 342%) compared to men (16%, 95% CI: -17, 62%; p sex-difference =0.006). Metabolic health did not alter the risk of either outcome among metabolically healthy or unhealthy individuals. Conclusions: Our longitudinal observations in a community-based sample suggest sex-related differences in the associations of variability of BMI and metabolic health on obesity and cardiometabolic risk. Additional investigations are warranted to replicate our findings and elucidate the biological basis for these sex-related differences. .