Associations between type 1 diabetes and autoimmune skin diseases: Mendelian randomization analysis

Type 1 diabetes mellitus (T1DM) may be associated with various autoimmune diseases, but the causal relationship between T1DM and autoimmune skin diseases is not yet clear.

The summary statistical data on T1DM and nine autoimmune skin diseases in European populations were extracted for mendelian randomization (MR) analysis. Subsequently, the analysis was replicated in East Asian populations. In the MR estimation, inverse variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were utilized. Outliers were excluded using MR-PRESSO, and horizontal pleiotropy was assessed with MR-Egger. Additionally, a multivariable MR analysis was conducted to investigate whether T1DM has an independent effect on autoimmune skin diseases after adjusting for potential confounders.

In Europe, the MR estimated based on IVW method indicated a causal association between genetically determined T1DM and systemic lupus erythematosus (SLE) (OR = 1.38, 95%CI: 1.26-1.50, p＜0.01), rheumatoid arthritis (RA) (OR = 1.15, 95%CI: 1.05-1.25, p＜0.01), as well as multiple sclerosis (MS) (OR = 1.17, 95%CI: 1.01-1.36, p = 0.04), but there is no association between T1DM and atopic dermatitis (AD), vitiligo, lichen planus (LP), hidradenitis suppurativa (HS), alopecia areata (AA) and systemic sclerosis (SS). After adjusting for time spent watching television, body mass index, type 2 diabetes mellitus, and body fat percentage, we found a causal relationship between T1DM and SLE (OR = 1.29, 95%CI: 1.16-1.44, p < 0.01), RA (OR = 1.28, 95%CI: 1.20-1.38 p < 0.01) and MS (OR = 1.11, 95%CI: 1.04-1.18, p < 0.01). Then, no genetic causal association was found between TIDM and SLE, and AD in East Asia. These results didn't exhibit horizontal pleiotropy, and "leave-one-out" analysis demonstrated result stability.

Our MR research indicates a causal relationship between T1DM and SLE, RA, and MS in Europe. However, no causal relationship between T1DM and SLE has been observed in East Asia. Therefore, it is important to regularly monitor relevant immunological markers of SLE, RA, and MS in T1DM patients and take preventive measures.