ArticleFrontiers in endocrinology2023
Association of epilepsy, anti-epileptic drugs (AEDs), and type 2 diabetes mellitus (T2DM): a population-based cohort retrospective study, impact of AEDs on T2DM-related molecular pathway, and via peroxisome proliferator-activated receptor γ transactivation.
Article in Frontiers in endocrinology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- The associations between epilepsy, metabolism, and their clinical implications.Frontiers in endocrinology · 2026Review
- Review
- Role and mechanism of mitochondrial dysfunction‑related gene biomarkers in the progression of type 2 diabetes mellitus.Molecular medicine reports · 2025Article
- MicroRNAs as Epigenetic Biomarkers of Pathogenetic Mechanisms of the Metabolic Syndrome Induced by Antiseizure Medications: Systematic Review.Journal of clinical medicine · 2025Review
- Analysis of the Correlation between Frailty Index, Clinical Characteristics, Use of Anti-Epileptic Drug, and Prognosis in Elderly Patients with Epilepsy.Actas espanolas de psiquiatria · 2025Article
- Mortality of Epilepsy in Chinese Populations: A Comprehensive Review.Neuroepidemiology · 2025Review
- Exploring the clinical connections between epilepsy and diabetes mellitus: Promising therapeutic strategies utilizing agmatine and metformin.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Identifying the genetic association between severe autoimmune type 2 diabetes and the risk of focal epilepsy.Frontiers in endocrinology · 2024Article
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Authors and funding
9 authors at 5 institutions in 1 country.
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Abstract
Introduction: A potential association between epilepsy and subsequent type 2 diabetes mellitus (T2DM) has emerged in recent studies. However, the association between epilepsy, anti-epileptic drugs (AEDs), and the risk of T2DM development remains controversial. We aimed to conduct a nationwide, population-based, retrospective, cohort study to evaluate this relationship. Methods: We extracted data from the Taiwan Longitudinal Generation Tracking Database of patients with new-onset epilepsy and compared it with that of a comparison cohort of patients without epilepsy. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing T2DM between the two cohorts. Next-generation RNA sequencing was used to characterize T2DM-related molecularchanges induced by AEDs and the T2DM-associated pathways they alter. The potential of AEDs to induce peroxisome proliferator-activated receptor γ (PPARγ) transactivation was also evaluated. Results: After adjusting for comorbidities and confounding factors, the case group (N = 14,089) had a higher risk for T2DM than the control group (N = 14,089) [adjusted hazards ratio (aHR), 1.27]. Patients with epilepsy not treated with AEDs exhibited a significantly higher risk of T2DM (aHR, 1.70) than non-epileptic controls. In those treated with AEDs, the risk of developing T2DM was significantly lower than in those not treated (all aHR ≤ 0.60). However, an increase in the defined daily dose of phenytoin (PHE), but not of valproate (VPA), increased the risk of T2DM development (aHR, 2.28). Functional enrichment analysis of differentially expressed genes showed that compared to PHE, VPA induced multiple beneficial genes associated with glucose homeostasis. Among AEDs, VPA induced the specific transactivation of PPARγ. Discussion: Our study shows epilepsy increases the risk of T2DM development, however, some AEDs such as VPA might yield a protective effect against it. Thus, screening blood glucose levels in patients with epilepsy is required to explore the specific role and impact of AEDs in the development of T2DM. Future in depth research on the possibility to repurpose VPA for the treatment of T2DM, will offer valuable insight regarding the relationship between epilepsy and T2DM.
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