Obesity may raise risk of autoimmune diseases

Individuals with obesity appears to be at greater risk of developing autoimmune diseases, according to a systematic review and meta-analysis. 

“Although definitive conclusions are still precluded for the single diseases, overall evidence supports obesity as a risk factor for autoimmunity,” the investigators said. 

The databases of PubMed and Embase were searched for studies that explored the relationship between obesity and the prevalence or incidence of autoimmune diseases. A total of 1,311 studies were identified, of which 26 (18 longitudinal and eight cross-sectional) were included in the meta-analysis. 

The investigators used generic inverse variance and fixed effect models to pool the adjusted odds ratios (ORs) of hazard ratios (HRs) with 95 percent confidence intervals (CIs) relating to the prevalence or incidence of autoimmune diseases in individuals with BMI >30 vs <25 kg/m2. 

Compared with normal weight, obesity significantly correlated with increased prevalence of rheumatoid arthritis (RA; OR, 1.11, 95 percent CI, 1.06‒1.16; p<0.00001) and psoriasis (OR, 1.35, 95 percent CI, 1.14‒1.59; p=0.0004). [Obesity 2026;34:36-50] 

Obesity also showed a significant association with a higher risk of developing RA (HR, 1.30, 95 percent CI, 1.15‒1.49; p<0.0001), psoriasis (HR, 1.18, 95 percent CI, 1.16‒1.20; p<0.00001), multiple sclerosis (MS; HR, 1.49, 95 percent CI, 1.25‒1.77; p<0.00001), and Crohn’s disease or ulcerative colitis (HR, 1.35, 95 percent CI, 1.11‒1.65; p<0.003). 

Furthermore, a significant association existed between obesity and the incidence of any autoimmune disease (HR, 1.41, 95 percent CI, 1.24‒1.62; p<0.00001). 

“[O]ur data suggest that individuals with obesity should be perceived as living with an increased risk of autoimmune diseases, an observation with public health implications, providing an additional scientific rationale to encourage obesity management and prevention at both the population and the clinical level,” the investigators said. 

Limitations 

These findings also suggest that the impact of obesity does not cover all autoimmune disorders, as shown by the lack of positive association with systemic lupus erythematosus (SLE). Although the number of SLE studies in the meta-analysis is small, a mechanistic possibility could be involved. 

“[W]hile RA, psoriasis, and MS are consistently characterized by an altered activation of the T cell compartment, SLE is now recognized to be mostly driven by the aberrant expansion and activation of autoreactive B cells, which may suggest different intermingling with obesity-driven inflammation,” the investigators said. [Nat Rev Rheumatol 2021;17:98-108] 

“On the other hand, the actual ‘autoimmune’ pathogenesis of some of the diseases we have here evaluated … is still not completely characterized, with self-antigens remaining elusive,” they added. 

Furthermore, most studies included in the meta-analysis did not account for factors such as diet, physical activity, genetic predisposition, and socioeconomic status, which might have significant associations with both obesity and autoimmune disease susceptibility. 

“Indeed, the association between obesity and autoimmune diseases appears more prominent in affluent countries (ie, North America and Europe), likely due to a combination of higher obesity rates, dietary patterns, and environmental influences that align with Western lifestyle,” the investigators said.  

“However, as obesity rates are rising in developing nations, a global shift in autoimmune disease burden may occur, necessitating further research into region-specific risk factors,” they added. [J Autoimmun 2010;34:J168-J177]