Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study

Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype.

The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models.

Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266–1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO.

Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.