'Metabolically Healthy Obesity' May Not Raise Mortality Risk

Miriam E. Tucker

July 23, 2018

Obesity in the absence of any other metabolic abnormalities does not raise the risk for all-cause mortality, new research suggests.

The latest study on the controversial concept of "metabolically healthy obesity" was published online July 12 in Clinical Obesity.

Using follow-up data from five cohort studies involving more than 50,000 adults, Jennifer L. Kuk, PhD, and colleagues conclude that "Obesity in the absence of metabolic abnormalities is not associated with increased risk for all-cause mortality as compared to normal weight individuals. In contrast, diabetes, hypertension, and dyslipidemia in isolation and in combination are more strongly associated with increased mortality risk."

Kuk, from the School of Kinesiology and Health Science at York University in Toronto, Ontario, Canada, and colleagues say that their results call into question whether individuals with metabolically healthy obesity benefit from weight loss.

Furthermore, "given the low success rates for obesity reduction and the stigma and bias experienced by those struggling with obesity, it may be particularly important to confirm whether obesity itself is associated with increased morbidity and mortality risk or reduced quality of life outcomes."

Contrast to Previous Studies

However, the new data seem to contradict those of some previous studies. For example, a recent study that used data from the Nurses' Health Study showed that obesity remains a risk factor for cardiovascular disease even among individuals who are otherwise "metabolically healthy," as did another study that relied on a large UK database.

At least part of the explanation for the difference in results is the strictness of the "metabolically healthy" definition used in the current study, Nathalie Eckel, MSc, lead author of the study that used Nurses' Health Study data, told Medscape Medical News. Relatively few people in the current study — only about 6% — had obesity but no clinical or preclinical elevations in glucose, lipids, or blood pressure.

"We used the absence of diabetes, hypertension, and hypercholesterolemia to define metabolic health and did not consider any preclinically elevated risk factors, while Kuk and colleagues did," said Eckel, of the German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. "Therefore, our study population might indeed be more 'unhealthy' compared to the study population in the more recent paper."

Moreover, Eckel noted, "While Kuk and colleagues used all-cause mortality as an outcome, we investigated cardiovascular disease events...Prior studies suggested that obesity is more strongly associated with cardiovascular disease than with total mortality."

The main message from both studies, Eckel said, is that "being 'metabolically unhealthy' — defined as having diabetes, hypertension, and/or hypercholesterolemia — is a stronger risk factor than obesity itself."

Just One Additional Risk Factor Makes a Difference

Kuk and colleagues examined data for 54,089 adults from five large longitudinal studies, including the Multi-Ethnic Study of Atherosclerosis and National Health and Nutrition Examination Survey III.    

Overall, 52% of the sample had more than one metabolic risk factor or obesity. Among those with obesity (body mass index ≥ 30 kg/m2), 5.8% had no other preclinical or clinical elevations in blood pressure, glucose, or lipids (using standard cutoffs).

Overall, there were 4864 (9.0%) deaths during 12.8 years of follow-up.

Obesity without other metabolic risk factors was not associated with increased mortality compared to lean individuals without risk factors (hazard ratio [HR], 1.10; 95% CI, 0.8 - 1.6).

Eckel noted that the strict definition used for "metabolically healthy obesity" in this study "results in a quite low precision for the risk estimate for metabolically healthy obese individuals compared to metabolically healthy normal-weight individuals…although the [overall] sample size was relatively large."

However, obesity combined with even just one other risk factor was associated with significantly increased mortality (HR, 1.80; 95% CI, 1.5 - 2.1).    

In the absence of obesity, diabetes (HR, 1.94; 95% CI, 1.2 - 3.1), preclinical hypertension (HR, 1.36; 95% CI, 1.1 - 1.7), hypertension (HR, 1.64; 95% CI, 1.4 - 1.9), and dyslipidemia (HR, 1.17; 95% CI, 1.0 - 1.3) were all significantly associated with increased all-cause mortality, compared with that of lean healthy individuals. In addition, mortality risk increased with increasing number of those risk factors.

When obesity was defined using waist circumference (≥ 88 cm for women, ≥ 102 cm for men), abdominal obesity alone was also not significantly associated with mortality compared to those without abdominal obesity or other metabolic risk factors (HR, 1.24; 95% CI, 0.9 - 1.7).  

However, when "metabolically healthy" was defined as either zero or one metabolic risk factor — as has been done in previous studies — metabolically healthy obesity was significantly associated with increased mortality risk compared to healthy and lean individuals (HR, 1.15; 95% CI, 1.01 - 1.32).

"Whether metabolically healthy individuals with obesity benefit from weight loss in terms of physical, functional, psychological, and metabolic outcomes needs to be confirmed in future research," Kuk and colleagues conclude.

The study by Kuk and colleagues was supported in part by the Canadian Institutes of Health Research. The study by Eckel and colleagues was funded by the US National Institutes of Health and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research. The authors have reported no additional relevant financial relationships.

Clin Obes. Published online July 12, 2018. Full text

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