ABSTRACT: The reported effects of a metabolically healthy obese (MHO) phenotype on diabetes and cardiovascular disease (CVD) risk are contradictory. Within the context of a population-based cohort study, we aimed to investigate the long-term risk of an MHO status for the development of diabetes and CVD, and whether consistency of this phenotype or age affected cardiometabolic outcomes. We recruited 7588 subjects without diabetes or CVD, aged 40 to 69 years at baseline examination, from the Korean Genome and Epidemiology Study, and followed-up these subjects for 10 years biennially. Participants were divided into 4 groups based on the body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). We defined persistent phenotypes if subjects maintained the same phenotype at every visit from baseline to their last visit. Incident diabetes and CVD morbidity or mortality were identified during 10 years of follow-up. Compared to MHNW controls, MUNW and MUO groups had increased risk for development of diabetes (hazard ratio [HR] 3.0 [95% CI: 2.5-3.6], and 4.0 [3.4-4.7], respectively) and CVD (HR 1.6 [1.3-2.0], and 1.9 [1.5-2.4], respectively). However, the MHO group showed only a marginal increase in risk for diabetes and CVD (HR 1.2 [0.99-1.6], 1.4 [0.99-1.8], respectively). The impact of MHO on the development of diabetes was more prominent in younger individuals (HR 1.9 [1.2-3.1] vs 1.1 [0.8-1.4], <45 years vs ?45 years at baseline). Only 15.8% of MHO subjects maintained the MHO phenotype at every visit from baseline to the 5th biennial examination (persistent MHO). In subjects with persistent MHO, the risk for diabetes and CVD was significantly higher than those with persistent MHNW (1.9 [1.2-3.1], 2.1 [1.2-3.7], respectively). MHO phenotype, even if maintained for a long time, was associated with a significantly higher risk for the development of diabetes and CVD in Korean subjects.
