'Metabolically Healthy' Obesity Still Puts Patients at Increased Risk of Adverse Health Outcomes

Data from the UK Biobank cohort details the increased risk of adverse health outcomes, including the development of diabetes and heart failure, among patients considered to have metabolically healthy obesity.

New research from the University of Glasgow suggests the concept of metabolically healthy obesity could be misleading, as data indicates these patients were still at increased risk of obesity-related adverse health outcomes.

An analysis of more than 380,000 individuals with a median follow-up of 11.2 years, results indicate patients considered to have metabolically healthy obesity were 4.3 times more likely to develop type 2 diabetes, 76% more likely to develop heart failure, and 18% more likely to suffer a heart attack or stroke during the follow-up period compared to their metabolically healthy counterparts without obesity.

"People with metabolically healthy obesity are not 'healthy' as they are at higher risk of heart attack and stroke, heart failure, and respiratory diseases compared with people without obesity who have a normal metabolic profile,” wrote investigators.

With the obesity epidemic continuing to swell, greater emphasis on research into different phenotypes of obesity could improve the existing knowledge base and care of patients. With this in mind, Frederick Ho, PhD, and colleagues from the Institute of Health and Wellbeing at the University of Glasgow designed the current study to assess associations of metabolically healthy obesity and obesity-related outcomes using data from the UK Biobank cohort.

A population-based prospective cohort study of more than 500,000 participants, the UK Biobank cohort contained data related to 381,363 participants who were not underweight and had complete data related to metabolic profile for inclusion in their analysis. Investigators planned to use Cox proportional hazards models to assess associations between metabolically healthy outcomes and health outcomes.

For the purpose of analysis, metabolically healthy obesity was defined as having a BMI of 30 kg/m2 or more and at least 4 of the 6 metabolically healthy criteria. These 6 markers used to define metabolic health were blood pressure, CRP, triglycerides, LDL-C, HDL-C, and HbA1c. Health outcomes of interest included incident diabetes and incident and fatal atherosclerotic cardiovascular disease (ASCVD), heart failure, and respiratory diseases.

Of the 381,363 participants included in the study, 54.7% (n=208,625) were considered metabolically healthy and of normal weight, 9.2% (n=35,103) had metabolically healthy obesity, 20.5% (78,259) were metabolically unhealthy without obesity, and 15.6% (n=59,376) were metabolically unhealthy with obesity.

In fully adjusted models, those with metabolically healthy obesity had a higher rates of incident heart failure (1.60; 95% CI, 1.45-1.75) and respiratory disease (HR, 1.20; 95% CI, 1.16-1.25) compared to those who were not obese at baseline. However, investigators noted this increased rate was not observed for ASCVD. Further analysis indicated these associations were generally weaker for fatal outcomes and only reached significance for all-cause (HR, 1.12; 95% CI, 1.04-1.21) and heart failure (HR, 1.44; 95% CI, 1.09-1.89) mortality rates.

Compared to those who were metabolically healthy without obesity, those with metabolically healthy obesity had greater rates of incident diabetes (HR, 4.32; 95% CI, 3.83-4.89), ASCVD (HR, 1.18; 95% CI, 1.10-1.27), heart failure (HR, 1.76; 95% CI, 1.61-1.92), respiratory diseases (HR, 1.28; 95% CI, 1.24-1.33) and all-cause mortality (HR, 1.22; 95% CI 1.14-1.31). Investigators also pointed out a subgroup analysis comparing those who transitioned from metabolically healthy obesity to metabolically unhealthy obesity during the follow-up to those considered metabolically healthy and of normal weight indicated these patients experienced greater rates of incident ASCVD (HR, 2.46; 95% CI, 1.12-5.41) and all-cause mortality (HR, 3.07; 95% CI, 1.44-6.56).

"Weight management could be beneficial to all people with obesity irrespective of their metabolic profile. The term 'metabolically healthy obesity' should be avoided in clinical medicine as it is misleading, and different strategies for defining risk should be explored,” wrote investigators.

This study, “Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants,” was published in Diabetologia.