Abstract
BACKGROUND: Multiple studies have suggested a potential association between multiple sclerosis (MS) and diabetes mellitus (DM). However, inconsistencies in the published literature-attributable to variations in statistical methods, sample size, and study design-have led to conflicting conclusions. Therefore, we conducted a systematic meta-analysis to clarify the relationship between MS and DM and to inform future mechanistic research. METHODS: We performed a comprehensive literature search in the Web of Science, PubMed, and Embase databases for studies investigating the relationship between MS and DM, covering the period from database inception to July 2025. Two researchers independently screened studies, extracted data, and assessed the risk of bias. Meta-analyses were conducted using Review Manager 5.3. RESULTS: Seven studies involving 3,143,619 participants were included. The meta-analysis did not reveal a statistically significant overall association between MS and DM (HR = 1.05,95%CI:0.88-1.27, P = 0.58). However, DM was associated with an increased risk of developing MS (HR = 1.59, 95%CI:1.24-2.05, P = 0.0003). Furthermore, patients with type 2 diabetes mellitus (T2DM) also showed an elevated risk of MS (HR = 1.46,95%CI:1.10-1.94, P = 0.008). CONCLUSIONS: Current evidence indicates that DM, specifically T2DM, increases the risk of developing MS. However, a reverse association remains unconfirmed.