Diabetes and Cardiovascular Disease Outcomes in the Metabolically Healthy Obese Phenotype: A cohort study

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.