SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Clinical Diabetes
Association Between Diabetes mellitus and Risk of Alzheimer's Disease: A meta-analysis and systematic review
Provisionally accepted
- 1chonggang general hospital, Chongqing, China
- 2Army Medical Center of PLA, Chongqing, China
- 3Yangjiaping Branch of Jiulongpo District People's Hospital, Chongqing, China
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Background Diabetes mellitus (DM) is hypothesized to increase the risk of Alzheimer's Disease(AD). However, existing studies have yielded conflicting results, with some demonstrating a significant association between DM and AD risk while others have not. Therefore, this meta-analysis aimed to systematically evaluate the association between DM and AD risk. Methods Comprehensive searches were conducted to identify cohort or case-control studies investigating the association between DM and AD risk. All eligible studies published before October 2025 were included. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias. Hazard ratio (HR) and 95% confidence interval (CI) were pooled as the effect size for meta-analysis. Statistical analyses were performed with RevMan 5.3 software. Results A total of eleven studies involving 3,393,545 participants were included. Meta-analysis revealed that DM was significantly associated with an increased risk of AD (HR = 1.36, 95% CI (1.19, 1.55), P < 0.00001). Subgroup analysis showed that DM increased the risk of AD regardless of sample size (< 100,000: HR = 1.33, 95% CI (1.11, 1.59), P = 0.002; > 100,000: HR = 1.39, 95% CI (1.13, 1.71), P = 0.002). The consistency in P values may be coincidental, and the results should be interpreted in conjunction with the high heterogeneity across studies. This association was consistent in both Asian (HR = 1.45, 95% CI: 1.20, 1.76, P < 0.00001) and non-Asian populations (HR = 1.29, 95% CI: 1.13, 1.48, P < 0.00001). After adjusting for APOE ε4 mutations, there was no statistically significant difference in the risk association between DM and AD (HR = 1.07, 95% CI (0.97, 1.19), P = 0.177), whereas without adjustment for APOE ε4 mutation, DM was associated with an increased AD risk (HR = 1.42, 95% CI (1.23, 1.64), P < 0.00001). Conclusion This meta-analysis provides compelling evidence that DM is an independent risk factor for AD, offering important implications for clinical practice and future research. However, due to the methodological limitations of this study, the results should be interpreted with caution. Large-scale, high-quality prospective cohort studies are needed to fully investigate the relationship between DM and AD risk.
Keywords: Alzheimer's disease, Dementia, Diabetes Mellitus, Meta-analysis, Systematic review
Received: 31 Oct 2025; Accepted: 06 Feb 2026.
Copyright: © 2026 Wu, Li, Qin and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Weiping Chen
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