Genetic influences, lifestyle and psychosocial aspects in relation to metabolically healthy obesity and conversion to a metabolically unhealthy state

Abstract

Aims: About 10%-30% of individuals with obesity are metabolically healthy, but the specific characteristics of the metabolically healthy obesity (MHO) phenotype remain unclear. We aimed to examine how physical activity, education, depressive symptoms and genetic predisposition to obesity differ between individuals with MHO and those with metabolically unhealthy obesity (MUO), and whether these factors predict stability in MHO or conversion to a metabolically unhealthy state.

Materials and methods: We retrieved data on 9809 individuals with obesity from the Health and Retirement Study collected between 2006 and 2016. We compared how physical activity, education, depressive symptoms and a polygenic score for higher body mass index (BMI) (PGS_BMI) differed cross-sectionally between MHO and MUO using logistic regression. We then examined if the same factors predict conversion to a metabolically unhealthy state over 4 years in individuals with MHO.

Results: Individuals with MHO had higher physical activity (odds ratio [OR] = 0.81), higher education (OR = 0.83) and lower depressive symptoms (OR = 1.14) compared to those with MUO but did not differ in the PGS_BMI. The associations were slightly attenuated in mutually adjusted models. None of the factors were associated with conversion from MHO to a metabolically unhealthy state. However, a higher PGS_BMI indicated 24% lower risk of conversion to a metabolically unhealthy state (p = 0.07).

Conclusions: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state.

Keywords: body mass index; metabolically healthy obesity; obesity; population study.

FIGURE 1

Cross‐sectional associations with metabolically unhealthy obesity. Odds ratios and 95% confidence intervals of MUO (metabolically unhealthy obesity) compared to MHO (metabolically healthy obesity) from cross‐sectional associations. All models were adjusted for age, sex, ethnicity and smoking. Separate models of physical activity, education and CES‐D (Center for Epidemiologic Studies Depression) scale in association with MUO included N = 7943 unique individuals with N = 12 014 observations in each model. The separate model of PGS_BMI (polygenic score for higher body mass index) and the mutually adjusted models included N = 4910 unique individuals and N = 9089 observations. BMI, body mass index.

FIGURE 2

Associations of conversion from metabolically healthy obesity to a metabolically unhealthy state. Odds ratios and 95% confidence intervals of conversion from MHO (metabolically healthy obesity) to a metabolically unhealthy state. All models are adjusted for age, sex, ethnicity and smoking. A separate model of physical activity, education and CES‐D (Center for Epidemiologic Studies Depression) scale as predictors of a metabolically unhealthy state included N = 536 unique individuals. The separate model of PGS_BMI (polygenic score for higher body mass index) as predictors of a metabolically unhealthy state and the mutually adjusted models included N = 380 unique individuals. BMI, body mass index.