Long-term metabolic risk for the metabolically healthy overweight/obese phenotype

BACKGROUND/OBJECTIVES: The clinical relevance of the metabolically healthy overweight/obese (MHO) phenotype is controversial and the relationships between weight change and the development of cardiometabolic risk factors is unknown. Therefore, we aim to: 1) Assess the long-term risk of developing one or more components of the metabolic syndrome in MHO adults compared with metabolically healthy normal weight (MHNW); 2) Evaluate risk of a composite of death, CVD, and risk of developing type 2 diabetes between adults defined according to baseline BMI and metabolic health. SUBJECTS/METHODS: Retrospective cohort study of adults 18–65 years of age seen at our institution between 1998 and 2000 who lived in Olmsted County. Metabolically healthy was defined as the absence of all components of the metabolic syndrome (except for waist circumference). Main outcome was the development of metabolic risk factors. The secondary outcome was a composite of mortality, CVD and heart failure. RESULTS: Of the 18071 individuals with complete data at baseline, 1805 (10%) were MHO (mean age 38 ± 11 years) and 3048 were MHNW (mean age 35 ± 11 years). After a median follow up of 15 years, IQR 10–17, 80% of MHO vs. 68% of MHNW developed at least one cardiometabolic risk factor (p < 0.001). In multivariate analysis, MHO individuals who gained ≥ 10% of their body weight were more likely to have developed metabolic complications compared to MHO individuals that did not gain weight (p=0.001 for 10–15%, p< 0.001 for > 15% weight gain). The risk for the secondary composite endpoint was similar between MHO and MHNW, number of events 218/1805 vs. 217/3048 for MHO and MHNW, respectively, (HR: 1.16, 95% CI 0.96–1.40). CONCLUSIONS: MHO are more likely to develop metabolic complications than MHNW, especially if they gain weight.