# Diabetes mellitus and risk of multiple sclerosis: a systematic review and meta-analysis

**Authors:** Maoqin Tang, Hongxue Tang, Haoyue Deng, Ruihan Liu, Gongjing He

PMC · DOI: 10.3389/fendo.2026.1724167 · Frontiers in Endocrinology · 2026-02-18

## TL;DR

This study finds that diabetes mellitus, especially type 2 diabetes, increases the risk of developing multiple sclerosis, but the reverse link is not confirmed.

## Contribution

The study provides a systematic meta-analysis clarifying the specific risk of MS in individuals with type 2 diabetes.

## Key findings

- Diabetes mellitus is associated with an increased risk of developing multiple sclerosis (HR = 1.59).
- Type 2 diabetes mellitus specifically elevates the risk of MS (HR = 1.46).
- No significant overall association was found between MS and diabetes mellitus.

## Abstract

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.

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.

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).

Current evidence indicates that DM, specifically T2DM, increases the risk of developing MS. However, a reverse association remains unconfirmed.

## Linked entities

- **Diseases:** multiple sclerosis (MONDO:0005301), diabetes mellitus (MONDO:0005015), type 2 diabetes mellitus (MONDO:0005148)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** demyelinating disease (MESH:D003711), hypertension (MESH:D006973), viral infections (MESH:D014777), Ischemic heart disease (MESH:D017202), immune system (MESH:D007154), Insulin resistance (MESH:D007333), T2DM (MESH:D003924), neuronal injury (MESH:D009410), IBD (MESH:D015212), system (MESH:D015619), MS (MESH:D009103), immune dysregulation (OMIM:614878), -cell dysfunction (MESH:D002292), autoimmune dysregulation (MESH:C580192), Chronic inflammation (MESH:D007249), complications (MESH:D008107), Comorbidity (MESH:D004194), metabolic disturbances (MESH:D024821), Hyperglycemia (MESH:D006943), dyslipidemia (MESH:D050171), neurotoxic (MESH:D020258), DM (MESH:D003920), ICD (OMIM:252500), autoimmune disease (MESH:D001327), Vascular complications (MESH:D003925), COPD (MESH:D029424), metabolic (MESH:D008659), neurological deficits (MESH:D009461), hypoxia (MESH:D000860)
- **Chemicals:** lipid (MESH:D008055), sphingolipid (MESH:D013107), vitamin D (MESH:D014807), AGEs (MESH:D017127), cholesterol (MESH:D002784), blood glucose (MESH:D001786)
- **Species:** Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12957073/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957073/full.md

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Source: https://tomesphere.com/paper/PMC12957073