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Metabolically Healthy Obesity Still Increases Diabetes Risk

Many people in this group become metabolically unhealthy later.

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A new study suggests that while it is possible to be both obese and healthy, this phenotype considerably increases the risk of getting diabetes, mainly because it is hard to maintain [1].

Chubby and happy?

Obesity is a known comorbidity in numerous chronic conditions, including age-related ones. It has been shown to positively correlate with cardiovascular diseases, metabolic disorders, dementia, and cancers: basically, all the major killers. However, this increase in risk does not affect every individual. Some obese people are perfectly metabolically healthy, just as many lean people are metabolically unhealthy. One meta-analysis found that 35% of obese people display a phenotype referred to asΒ  metabolically healthy obesity (MHO) [2].

Given the name, it is reasonable to believe that metabolically healthy obese people may be off the hook, can stop worrying about the possible health consequences of their weight, and can just enjoy living. One study found no increased risk of cardiovascular diseases in people with MHO compared to healthy lean people [3]. Another study reported largely similar results for CVD and diabetes [4]. However, other recent studies reached the opposite conclusion [5]. A new study published in Diabetes, Obesity, and Metabolism utilizes data from a large-scale longitudinal study to answer this question.

1.5 times higher risk

In the early 2000s, the Korean Genome and Epidemiology study enrolled around 10,000 people aged 49-60 to investigate risk factors for chronic diseases. The study is still ongoing, and follow-up data is collected every two years. The researchers identified 6265 people with obesity and excluded those who had had serious diseases or conditions at baseline. Interestingly, obesity phenotypes were determined using not only the body mass index (BMI) but also waist circumference and body fat percentage, which might be more accurate criteria than BMI.

The study population was divided into three more subgroups in addition to MHO: metabolically unhealthy obesity (MUO), metabolically healthy normal weight (MHNW), and metabolically unhealthy normal weight (MUNW). The researchers controlled for several confounding variables, including a polygenic score of predisposition to diabetes. Other potential covariates included age, sex, education levels, smoking, drinking, physical activity, diet quality, total energy intake, and several clinical markers.

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Close to 40% of the obese participants fell into the MHO category. Unsurprisingly, MHO participants were generally younger and more likely to engage in physical activity. They were also more educated, which often correlates with healthier lifestyles.

During the follow-up period, 903 cases of diabetes onset were identified. In the unadjusted model, the risk of diabetes compared to metabolically healthy people with normal weight was 1.7 times higher for MHO, 2.5 times higher for MUNW, and 3.6 times higher for MUO. After adjusting for the covariates, people with MHO were still 1.5 times more likely to develop diabetes than MHNW, with smoking and genetic predisposition exacerbating the ratio. The risk remained unchanged even when people who developed diabetes during the first five years of follow-up were excluded to preempt a reverse association.

Staying obese and healthy is hard

In agreement with some other longitudinal studies, this one suggests that metabolically healthy obesity is often a transient phenotype. At the end of the follow-up period (16 years), 53% of MHO people had joined the MUO category (although some had moved to MHNW), despite them leading healthier lifestyles on average. This transition probably explains most of the increased risk of diabetes. One earlier meta-analysis found that metabolically healthy obese people had an almost two-fold higher risk of transitioning to a metabolically unhealthy state than metabolically healthy lean people.

While those findings are valid at a populational level, every person is different, and a person can reasonably hope to stay healthy despite being overweight. However, losing weight seems a much safer bet.

In conclusion, our results indicate that, even when considering obesity phenotype as a time-varying exposure, individuals with MHO are still at higher risk for developing diabetes than those with MHNW. As such, to reduce health risks, individuals with MHO should strive to avoid transitioning to metabolically unfavourable conditions and should make efforts to reduce and maintain their body weight within a normal range.

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Literature

[1] Lee, H. A., & Park, H. (2023). Metabolically healthy obese individuals are still at high risk for diabetes: Application of the marginal structural model. Diabetes, Obesity and Metabolism.

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[2] Lin, H., Zhang, L., Zheng, R., & Zheng, Y. (2017). The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: a PRISMA-compliant article. Medicine, 96(47).

[3] Meigs, J. B., Wilson, P. W., Fox, C. S., Vasan, R. S., Nathan, D. M., Sullivan, L. M., & D’Agostino, R. B. (2006). Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. The Journal of Clinical Endocrinology & Metabolism, 91(8), 2906-2912.

[4] Appleton, S. L., Seaborn, C. J., Visvanathan, R., Hill, C. L., Gill, T. K., Taylor, A. W., … & North West Adelaide Health Study Team. (2013). Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes care, 36(8), 2388-2394.

[5] Zhou, Z., Macpherson, J., Gray, S. R., Gill, J. M., Welsh, P., Celis-Morales, C., … & Ho, F. K. (2021). Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants. Diabetologia, 64(9), 1963-1972.

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About the author
Arkadi Mazin

Arkadi Mazin

Arkadi is a seasoned journalist and op-ed author with a passion for learning and exploration. His interests span from politics to science and philosophy. Having studied economics and international relations, he is particularly interested in the social aspects of longevity and life extension. He strongly believes that life extension is an achievable and noble goal that has yet to take its rightful place on the very top of our civilization’s agenda – a situation he is eager to change.