Rethinking Obesity, Inflammation, and Disease Risk
Body mass index (BMI) has long been used to assess whether a person falls within a healthy weight range, but growing evidence suggests that BMI alone may not fully capture an individual’s health risks.
A new study published in Nature Medicine highlights just how different those risks can be. Researchers analyzed health data from nearly 200,000 adults with overweight or obesity and developed a risk prediction tool called OBSCORE designed to estimate an individual’s likelihood of developing 18 obesity-related complications, including type 2 diabetes, cardiovascular disease, chronic kidney disease, and sleep apnea (1).
The researchers found that people with similar BMIs often had dramatically different future health risks.
In some cases, individuals classified within the same BMI category fell into entirely different risk groups, suggesting that body weight alone may overlook important biological and clinical differences that influence long-term health outcomes.
One of the study’s most striking findings was the degree of variation observed within BMI categories. The highest-risk group identified by OBSCORE had a 47-fold greater risk of cardiovascular death than the lowest-risk group, despite all participants already meeting criteria for overweight or obesity.
While obesity is often discussed in terms of body weight, scientists increasingly recognize it as a condition that can influence immune function throughout the body.
Adipose tissue, commonly known as body fat, is now understood to be an active endocrine and immune organ that produces signaling molecules that influence inflammation and metabolism (3). As obesity develops, immune cell populations within adipose tissue shift toward a more inflammatory state, with increased numbers of macrophages, Th1 cells, and Th17 cells and reduced activity of regulatory immune pathways that normally help maintain immune balance (2,3).
Researchers have proposed that these immune changes may help explain why obesity has been linked to a variety of chronic inflammatory conditions (2,3).
The Growing Link Between Obesity and Autoimmune Disease
Interest in the connection between obesity and autoimmunity has grown substantially over the past two decades.
Several biological mechanisms may contribute to this relationship. Obesity is associated with increased production of inflammatory molecules such as TNF-α and IL-6 as well as altered levels of hormones known as adipokines, which help regulate interactions between metabolism and the immune system (3).
One adipokine, leptin, has attracted particular attention because it promotes inflammatory T-cell responses while suppressing regulatory T cells that normally help prevent excessive immune activation (3).
A recent systematic review and meta-analysis published in Obesity analyzed data from 26 studies involving more than 1.9 million participants and found that obesity was associated with a significantly increased risk of developing autoimmune diseases overall (4). Compared with individuals in the BMI category traditionally classified as normal weight, people with obesity had a 30% higher risk of developing rheumatoid arthritis, a 49% higher risk of multiple sclerosis, a 35% higher risk of Crohn’s disease, and an 18% higher risk of psoriasis.
When researchers combined data across autoimmune diseases, obesity was associated with a 41% increased risk of developing an autoimmune condition overall (4).
Researchers have also observed high rates of overweight and obesity among children and adolescents with chronic autoimmune thyroiditis, further highlighting growing interest in the relationship between metabolic health and autoimmunity (5).
Obesity has also been associated with worse outcomes in some autoimmune conditions after diagnosis. In rheumatoid arthritis, studies have linked obesity to greater symptom burden, higher levels of disability, elevated inflammatory markers, and lower rates of remission (6).
Looking Beyond BMI Toward More Personalized Risk Assessment
Despite these associations, not every person with obesity develops metabolic disease, cardiovascular disease, or autoimmune conditions. Likewise, some individuals with relatively modest increases in body weight experience significant health complications.
The OBSCORE model was designed to help explain these differences by incorporating a broader range of clinical and biological information than BMI alone (1).
Rather than treating everyone within a BMI category as having similar risks, the model attempts to identify which individuals are most likely to develop serious complications in the future.
These findings suggest that BMI may be useful as a screening tool but may not fully capture the biological complexity underlying disease risk, reflecting a broader shift toward precision medicine, an approach that seeks to move beyond one-size-fits-all measures and better account for individual differences in biology and health.
Citations
- Demircan, K., Carrasco-Zanini, J., Williamson, A. et al. Data-driven prioritization of high-risk individuals for weight loss interventions. Nat Med (2026). https://doi.org/10.1038/s41591-026-04353-2
- Endo, Y., Yokote, K., & Nakayama, T. (2017). The obesity-related pathology and Th17 cells. Cellular and molecular life sciences : CMLS, 74(7), 1231–1245. https://doi.org/10.1007/s00018-016-2399-3
- Taylor E. B. (2021). The complex role of adipokines in obesity, inflammation, and autoimmunity. Clinical science (London, England : 1979), 135(6), 731–752. https://doi.org/10.1042/CS20200895
- Spatocco, I., Mele, G., De Rosa, G., Fusco, C., Ruggiero, K., Pellegrini, V., Carreras, F., La Grotta, R., Ceriello, A., Procaccini, C., Matarese, G., Prattichizzo, F., & de Candia, P. (2026). Obesity as a Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis. Obesity (Silver Spring, Md.), 34(1), 36–50. https://doi.org/10.1002/oby.70044
- González-Mereles, A. P., Arguinzoniz-Valenzuela, S. L., López-López, A. P., Maqueda-Tenorio, S. E., & González-Baqué, I. (2021). Overweight and obesity in children and adolescents with chronic autoimmune thyroiditis. Sobrepeso y obesidad en niños y adolescentes con tiroiditis crónica autoinmunitaria. Boletin medico del Hospital Infantil de Mexico, 78(5), 424–431. https://doi.org/10.24875/BMHIM.20000292
- Poudel, D., George, M. D., & Baker, J. F. (2020). The Impact of Obesity on Disease Activity and Treatment Response in Rheumatoid Arthritis. Current rheumatology reports, 22(9), 56. https://doi.org/10.1007/s11926-020-00933-4