A large cohort study in the U.K. provided new evidence that “metabolically healthy” obesity is not so healthy after all.
Among 381,363 individuals followed for a median of 11 years, metabolically healthy obese individuals had a significantly higher risk for incident diabetes (HR 4.32, 95% CI 3.83-4.89), atherosclerotic cardiovascular disease (HR 1.18, 95% CI 1.10-1.27), and heart failure (HR 1.76, 95% CI 1.61-1.92) compared with metabolically healthy non-obese individuals, reported Frederick Ho, PhD, of the University of Glasgow in Scotland, and colleagues.
As shown in the study online in Diabetologia, metabolically healthy individuals had a higher risk for respiratory diseases (HR 1.28, 95% CI 1.24-1.33) and all-cause mortality (HR 1.22, 95% CI 1.14-1.31), and approximately one-quarter of metabolically healthy obese individuals became metabolically unhealthy within 3-5 years.
“The key point, therefore, is that the risk of many important outcomes, such as heart failure and respiratory disease, is elevated in people with obesity even if they have a normal metabolic profile. Using the label ‘metabolically healthy’ to describe this group in clinical medicine is misleading and therefore should be avoided,” the researchers wrote.
“These findings, as well as the unstable nature of MHO [metabolically healthy obesity], suggest that weight management could be beneficial for people with obesity even if they do not currently show abnormalities in their metabolic profile,” the team continued. “Weight management strategies include lifestyle changes, such as diet and physical activity, concomitant pharmacotherapies upon risk assessment, or bariatric surgery in severe obesity.”
The data came from the U.K. Biobank, a population-based, prospective cohort study made up of individuals from the general population of England, Scotland, and Wales. Height and weight were measured by trained staff, and individuals with a body-mass index (BMI) of 30 or higher were classified as obese.
For obese individuals to be classified as metabolically healthy, they had to be in the normal range for at least four of six metabolic markers: blood pressure, glycated hemoglobin, low-density lipoprotein and high-density lipoprotein cholesterol, C-reactive protein, and triglycerides. These were all measured at a central lab during 2014-2017.
Of the total 381,363 individuals in the database, the researchers identified 35,103 metabolically healthy obese individuals, which was approximately 9% of the cohort, as well as 59,376 metabolically unhealthy obese individuals (15.6% of the cohort) and 208,625 non-obese healthy individuals (55%).
Ho’s group used Cox proportional hazards models to look for associations linking obesity, metabolic health, and health outcomes, adjusting for factors that included age, sex, ethnicity, smoking, alcohol intake, physical activity, and dietary habits. The main outcomes included incident diabetes, cardiovascular disease, and mortality.
Metabolically healthy obesity was in general associated with lower risk for negative health outcomes than metabolically unhealthy obesity, the researchers said. For example, metabolically healthy obese individuals had approximately one-third the risk of incident diabetes compared with their metabolically unhealthy obese counterparts (HR 4.32 vs 12.86). Metabolically healthy obese individuals also tended to be younger, more active, and have higher levels of education.
A sub-analysis of 8,521 individuals who had longitudinal BMI and metabolic data over a median of 4.4 years found that more than one-quarter of metabolically healthy obese individuals became metabolically unhealthy (exact figure not reported). Another 20% lost weight and became non-obese, the researchers said.
However, the sub-analysis also identified some metabolically healthy obese individuals who appeared not to be at higher risk for adverse outcomes, at least in the short term. “It is worth noting that half of the participants remained with MHO after 4.4 years of follow-up. We could not detect any significant elevated risk among them compared with people who were metabolically healthy and non-obese throughout the study. It is likely that this group of people are at lower risk than people with other MHO trajectories,” the investigators wrote.
“However,” they added, “since there were not sufficient numbers of events, we cannot conclude whether they were at the same risk as people with MHN [metabolically healthy non-obesity], or were at a modestly elevated risk. Future prospective studies should consider this research question.”
Key limitations of the study, the team said, were that fasting glucose and insulin resistance were not measured, which limited how well the researchers could define metabolic health. In addition, the study did not consider other potential markers of metabolic health such as genetic data or hospitalizations.
Last Updated June 10, 2021
No funding sources were indicated for the study. The U.K. Biobank was established by the Wellcome Trust, the Medical Research Council, the Department of Health, the Scottish government, and the Northwest Regional Development Agency.
Ho reported no potential conflicts of interest.