Diabetes and Cardiovascular Disease Outcomes in the Metabolically Healthy Obese Phenotype

OBJECTIVE To determine the correlates of the "metabolically healthy obese" (MHO) phenotype and the longitudinal risks of diabetes and cardiovascular disease (CVD)/stroke associated with this phenotype. RESEARCH DESIGN AND METHODS The North West Adelaide Health Study is a prospective cohort study of 4,056 randomly selected adults aged ≥ 18 years. Participants free of CVD/stroke and not underweight (n = 3,743) were stratified by BMI categories and metabolic risk, defined as having two or more International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. RESULTS Correlates of the MHO (n = 454 [12.1%]) included smoking, socioeconomic disadvantage, and physical inactivity. Compared with metabolically healthy normal-weight subjects (n = 1,172 [31.3%]), the MHO were more likely to develop metabolic risk (15.5 vs. 33.1%, P < 0.001) and incident diabetes (odds ratio 2.09 [95% CI 0.87-5.03]) but not CVD/stroke (1.16 [0.58-2.29]) during 5.5-10.3 years of follow-up. These risks were not seen in MHO subjects maintaining metabolic health (n = 188 [67%]). Sustained metabolic health in obese participants was associated with age ≤ 40 years and lower waist circumference. Compared with the metabolically at-risk obese, MHO women demonstrated a significantly higher (mean [SE]) percentage of leg fat (49.9 [0.5] vs. 53.2 [0.7]) and lower waist circumference (104 [0.6] vs. 101 cm [0.8]), despite no significant differences in overall adiposity. CONCLUSIONS "Healthy" obesity was a transient state for one-third of subjects. Persistence of a MHO phenotype, which was associated with favorable outcomes, was related to younger age and a more peripheral fat distribution. The MHO phenotype may be sustained by promoting lower waist circumferences.