A Better Definition of Metabolically Healthy Obesity?

A proposed new definition of metabolically healthy obesity uses waist-to-hip ratio as a key measurement for identifying individuals classified as obese by body mass index (BMI) who were not at increased mortality risk.

A team led by Matthias Schulze, DrPH, of the German Institute of Human Nutrition Potsdam-Rehbruecke, developed the new definition using data from the third National Health and Nutrition Examination Survey (NHANES) and validated the change in a cohort from the U.K. Biobank.

The new definition, as explained in the study online in JAMA Network Open, has three components:

• Systolic blood pressure less than 130 mm Hg and no use of blood pressure–lowering medication

• Waist-to-hip ratio less than 0.95 for women and less than 1.03 for men

• No existing type 2 diabetes

The researchers found that 40% of obese individuals in the NHANES cohort met this definition of metabolically healthy obesity, which was not significantly associated with cardiovascular mortality (HR 0.68, 95% CI 0.30-1.54) or total mortality (HR 1.03, 95% CI 0.70-1.51) compared with metabolically healthy normal-weight individuals after more than 14 years of follow up.

In the U.K. Biobank cohort, 20% of obese individuals met the new definition and were not at increased risk for cardiovascular mortality (HR 1.17, 95% CI 0.81-1.69) or total mortality (HR 0.98, 95% CI 0.87-1.10) after nearly 8 years of follow up. The U.K. cohort was self-selected and had a higher mean age, which may explain the different proportions of individuals meeting the new definition between the two groups, the investigators noted.

They explained that a precise definition of metabolically healthy obesity has been difficult to pin down, and that past definitions have relied heavily on the absence of the metabolic syndrome or insulin resistance with various criteria and cutoffs.

“In the present study, MHO [metabolically healthy obesity] defined by either of these two definitions showed inconsistent results among both cohorts, and the associations were not independent of our new definition; however, our definition was associated with the risk of mortality independently of other definitions,” the investigators wrote. “This finding suggests that our definition better distinguishes between at-risk and not-at-risk individuals.

“Our results, however, also indicate that our definition may only be able to identify a low-risk MHO phenotype among individuals with a BMI less than 40. Higher mortality was observed for people with severe obesity (BMI > 40), irrespective of metabolic health,” the researchers added.

Writing in an accompanying commentary, Ayana April-Sanders, PhD, and Carlos Rodriguez, MD, MPH, both of Albert Einstein College of Medicine in the Bronx, New York, elaborated on the reasons waist-to-hip ratio was an optimal measurement for defining metabolically healthy obesity compared with other measurements of body fat.

“Although easy to measure, BMI is considered an insufficient measure of body fat content because it fails to account for muscle mass and bone density and does not reflect fat distribution. Waist circumference is commonly used to capture abdominal obesity in prior MHO definitions; however, WHR [waist-to-hip ratio] is a more effective measurement of central adiposity, with WHR having the strongest gradient with incident CVD because not all excess weight is the same and will differ in its association with health risks,” the commentators said.

“The present study provides the much-needed evidence to support establishing a standardized definition of MHO as the first step in understanding obesity phenotypes. There are several other issues to address to help move this area of research forward,” April-Sanders and Rodriguez added.

Schulze’s group noted an apparent surprising finding of the study, that measures of dyslipidemia were not significantly associated with mortality in the cohorts analyzed. Dyslipidemia was therefore not included in the new definition.

“Although this lack of inclusion seems surprising considering the well-known association between dyslipidemia and increased risk of death and CVD, associations between total cholesterol level and vascular mortality are weaker among participants with obesity compared with other BMI categories,” the researchers wrote.

The study included 12,341 individuals from the NHANES cohort and 374,079 from the U.K. Biobank. Included were all non-pregnant participants in the databases ages 18 to 75 with no history of cardiovascular disease, who had a BMI of 18.5 or higher, and who fasted 6 or more hours before examination in NHANES-III.

Participants in the U.K. Biobank cohort who did not have blood measurements were excluded, the study was conducted from 2015 to 2020, and obesity was defined as a BMI of 30 or higher. The researchers used area under the receiver operating characteristic and the Youden index to identify factors predictive of mortality.

Key limitations of the study, Schulze and co-authors said, included the lack of data on changes in body weight and metabolic factors due to the original design of NHANES-III. It was not possible, therefore, to assess the impact of changes in these factors on metabolic health and cardiovascular risk. In addition, body fat distribution may differ according to race and ethnicity, and the proposed waist-to-hip ratio cutoffs might not be applicable to all populations, especially Asian populations, which were underrepresented in both cohorts.