Mendelian Randomization Links T1D to Increased Risk of Arthritis, MS

Results from a Mendelian randomization analysis suggest type 1 diabetes was associated with a significant increase in the likelihood of multiple autoimmune skin conditions, including rheumatoid arthritis (RA) and multiple sclerosis (MS).

An analysis of 9 autoimmune skin diseases in people with type 1 diabetes of European ancestry, which was then replicated in East Asian populations, results provide an overview of the topic, with people with type 1 diabetes at increased likelihood of RA and MS, but not for atopic dermatitis, vitiligo, or alopecia areata.¹

“The most effective method for preventing and reducing the occurrence of autoimmune skin diseases is targeted control of the risk factors,” wrote investigators.¹ “Therefore, it is essential to proficiently recognize unconventional risk factors to enhance the prevention and management of autoimmune skin conditions.”

An autoimmune disorder characterized by impaired beta cell function and insulin production, prior research has suggested people with type 1 diabetes carry a greater risk for many other conditions as a result of the condition, as is common with autoimmune disorders. However, as noted by Xiaolan Li, MD, PhD, of the Department of Dermatology and Venereology at The Second Affiliated Hospital of Kunming Medical University, and fellow investigators, less research has been conducted into the causal relationship between type 1 diabetes and autoimmune skin diseases.^1,2

Leveraging the National Human Genome Research Institute’s Genome-Wide Association Studies (GWAS) Catalog, investigators designed their study with the intent of performing 2-sample mendelian randomization analysis for type 2 diabetes and 9 other autoimmune conditions. Investigators sought to validate these findings by repeating this analysis among East Asian populations using data from the GWAS Catalog and other databases. Of note, investigators also performed a multivariable analysis to determine the independent effect of type 1 diabetes on each autoimmune skin condition with adjustment for potential confounders.¹

Among European populations, investigators found a causal association between type 1 diabetes and systemic lupus erythematous (SLE) (Odds Ratio [OR], 1.38; 95% CI, 1.26 to 1.50; P＜.01), RA (OR, 1.15; 95% CI, 1.05 to 1.25; P＜.01), and MS (OR, 1.17; 95% CI, 1.01 to 1.36; P = .04). There was no association observed for type 1 diabetes and atopic dermatitis, vitiligo, lichen planus, hidradenitis suppurativa, alopecia areata, and systemic sclerosis.¹

Upon adjustment fortime spent watching television, body mass index, type 2 diabetes mellitus, and body fat percentage, results offered evidence suggesting the presence of a causal relationship between type 1 diabetes and SLE (OR, 1.29; 95% CI, 1.16 to 1.44; P <.01), RA (OR, 1.28; 95% CI, 1.20 to 1.38; P <.01), and MS (OR, 1.11; 95% CI, 1.04 to 1.18; P <.01).¹

However, investigators pointed out that replication of these analyses among East Asian populations found no genetic causal association between type 1 diabetes and SLE.¹

“Our [Mendelian randomization] research indicates a causal relationship between [type 1 diabetes mellitus] and SLE, RA, and MS in European populations, with no evidence of a causal link between [type 1 diabetes] and atopic dermatitis, vitiligo, lichen planus, hidradenitis suppurativa, alopecia areata, and systemic sclerosis," investigators wrote.¹ "Therefore, it is important to regularly monitor relevant immunological markers of SLE, RA, and MS in [type 1 diabetes mellitus] patients and take preventive measures.”

References:

1. Liu J, Xu Y, Liu Y, Zhu Y, Li X. Associations between type 1 diabetes and autoimmune skin diseases: Mendelian randomization analysis. Heliyon. 2024;10(12):e32781. Published 2024 Jun 10. doi:10.1016/j.heliyon.2024.e32781
2. Conrad N, Misra S, Verbakel JY, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet. 2023;401(10391):1878-1890. doi:10.1016/S0140-6736(23)00457-9