Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study.

The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favourable metabolic profile. Its prognostic value is unclear and may depend on the health outcome being examined. We examined the association of MHO phenotype with incident cardiovascular disease (CVD) and type 2 diabetes

Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study

Objective To describe 20-year risk factor trajectories according to initial weight/health status and investigate the extent to which baseline differences explain greater mortality among metabolically healthy obese (MHO) individuals than healthy non-obese individuals. Methods The sample comprised 6529 participants in the Whitehall II study who were measured serially between 1991–1994 and 2012–2013. Baseline weight (non-obese or obese; body mass index (BMI) ≥30 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance (HOMA-IR)) were defined. The relationships of baseline weight/health status with 20-year trajectories summarizing ~25,000 observations of systolic and diastolic blood pressures, HDL-C, triglycerides, glucose, and HOMA-IR were investigated using multilevel models. Relationships of baseline weight/health status with all-cause mortality up until July 2015 were investigated using Cox proportional hazards regression. Results Trajectories tended to be consistently worse for the MHO group compared to the healthy non-obese group (e.g., glucose by 0.21 (95% CI 0.09, 0.33; p < 0.001) mmol/L at 20-years of follow-up). Consequently, the MHO group had a greater risk of mortality (hazard ratio 2.11 (1.24, 3.58; p = 0.006)) when the referent group comprised a random sample of healthy non-obese individuals. This estimate, however, attenuated (1.34 (0.85, 2.13; p = 0.209)) when the referent group was matched to the MHO group on baseline risk factors. Conclusions Worse baseline risk factors may explain any difference in mortality risk between obese and non-obese groups both labelled as healthy, further challenging the concept of MHO

Early determinants of metabolically healthy obesity in young adults:study of the Northern Finland Birth Cohort 1966

Abstract Background: A body of literature suggests a metabolically healthy phenotype in individuals with obesity. Despite important clinical implications, the early origins of metabolically healthy obesity (MHO) have received little attention. Objective: To assess the prevalence of MHO among the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years of age, examine its determinants in early life taking into account the sex specificity. Methods: We studied 3205 term-born cohort participants with data available for cardio-metabolic health outcomes at 31 years, and longitudinal height and weight data. After stratifying the population by sex, adult BMI and a strict definition of metabolic health (i.e., no risk factors meaning metabolic health), we obtained six groups. Repeated childhood height and weight measures were used to model early growth and early adiposity phenotypes. We employed marginal means adjusted for mother and child covariates including socio-economic status, birth weight and gestational-age, to compare differences between the groups. Results: The prevalence of adult MHO was 6% in men and 13.5% in women. Differences in adult metabolic status were linked to alterations in BMI and age at adiposity peak in infancy (p &lt; 0.0003 in men and p = 0.027 in women), and BMI and age at adiposity rebound (AR) (p &lt; 0.0001 irrespective of sex). Compared to MHO, metabolically unhealthy obese (MUO) women were five and a half months younger at AR (p = 0.007) with a higher BMI while MUO men were four months older ( p = 0.036) with no difference in BMI at AR. Conclusion: At the time of AR, MHO women appeared to be older than their MUO counterparts while MHO men were younger. These original results support potential risk factors at the time of adiposity rebound linked to metabolic health in adulthood. These variations by sex warrant independent replication