A Simple New Definition for 'Metabolically Healthy Obesity'?

Marlene Busko

May 07, 2021

Scientists have proposed a simple new definition for "metabolically healthy obesity" to identify individuals who do not have an increased risk of cardiovascular disease (CVD) death and total mortality.

The team — led by Anika Zembic, MPH, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany — performed an assessment of anthropometric and metabolic risk factors as well as mortality data from two cohorts that "yielded a simple definition to categorize participants with obesity as metabolically healthy or unhealthy."

They defined "metabolically healthy" as systolic blood pressure < 130 mm Hg and no use of blood pressure-lowering medication; waist-to-hip ratio < 0.95 (in women) and < 1.03 (in men); and no prevalent type 2 diabetes.

Based on this new definition, 42% of participants in the third US National Health and Nutrition Examination Survey (NHANES-III) and 19% of participants in the UK Biobank study had metabolically healthy obesity and did not have an increased risk for CVD mortality and total mortality compared with individuals with metabolically healthy normal weight.  

"People with a phenotype defined as metabolically unhealthy using this definition had significantly higher hazard ratios for [CVD] mortality and total mortality irrespective of body mass index (BMI) category, and people with phenotypes defined as having metabolically healthy obesity displayed no increased risk," Zembic and colleagues summarize in their article, published May 7 in JAMA Network Open.

"Our new definition may be important not only to stratify risk of mortality in people with obesity, but also in people with overweight and normal weight," they conclude.

Thirty Different Definitions of "Metabolically Healthy Obesity"

"To date, there is no universally accepted standard for defining [metabolically healthy obesity] and more than 30 different definitions have been used to operationalize the phenotypes in studies," which may explain the "continued unresolved debate" about outcomes in patients with metabolically unhealthy obesity, Ayana K. April-Sanders, PhD, and Carlos J. Rodriguez, MD, MPH, from Albert Einstein College of Medicine, New York City, write in an accompanying commentary.

The current study, they note, suggests that waist-to-hip ratio is a better measure of central adiposity than waist circumference, and that the effect of dyslipidemia on CVD mortality may be weaker among individuals with obesity.

However, the findings may not be generalizable to other CVD outcomes, they caution.

And importantly, some individuals with metabolically healthy obesity will likely transition to unhealthy obesity over time due to weight gain, aging, and lack of physical activity.

Therefore, "the present study provides a prototype of how that definition can be derived, but more rigorous tests and evidence using similar techniques are needed, particularly in prospective studies," according to April-Sanders and Rodriguez.

They call for more research to establish a standardized definition of metabolically healthy obesity and then, using that definition, to determine the prevalence of healthy and unhealthy obesity and identify factors that preserve healthy obesity. 

Definition Developed From NHANES Cohort, Validated in UK Biobank

Zembic and colleagues explain that previous definitions for metabolically healthy obesity were mainly based on the absence of either metabolic syndrome or insulin resistance, but some individuals with obesity but without metabolic disease still have increased risks of CVD mortality and total mortality.

To develop a more precise definition of metabolically healthy obesity, the researchers analyzed data from 12,341 individuals in the United States who participated in NHANES-III, conducted between 1988 and 1994. The individuals were a mean age of 42 and 51% were women, and they were followed for an average of 14.5 years.  

The researchers validated this definition using data from 374,079 individuals in the population-based UK Biobank cohort who were assessed in 2006 to 2010. Those individuals were a mean age of 56 and 55% were women, and they were followed for a mean of 7.8 years.

The combination of systolic blood pressure and waist-to-hip ratio had the strongest association with CVD mortality and total mortality, and the prevalence of type 2 diabetes was also associated with greater risk.

Regardless of BMI, all groups of metabolically unhealthy individuals had increased risks of CVD mortality and total mortality.

The study and some of the researchers were supported by grants from the German Federal Ministry of Education and Research.  

JAMA Open Netw. Published online May 7, 2021. Article, Commentary

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