Evidence map›Paper›PMID 37334286›Full record

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.

Ni Tien, Tien-Yuan Wu, Cheng-Li Lin, Fang-Yi Chu, Charles C N Wang, Chung Y Hsu, Fuu-Jen Tsai, Yi-Jen Fang, Yun-Ping Lim

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
8.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Ni TienDepartment of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
Tien-Yuan WuGraduate Institute of Clinical Pharmacy, College of Medicine, Tzu Chi University, Hualien, Taiwan.
Cheng-Li LinManagement Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
Fang-Yi ChuDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
Charles C N WangDepartment of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
Chung Y HsuGraduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Fuu-Jen TsaiSchool of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
Yi-Jen FangResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yun-Ping LimDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
China Medical University · TWChina Medical University Hospital · TWAsia University · TWNational Chung Hsing University · TWTzu Chi University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Diabetes Mellitus, Type 2EpilepsyAnticonvulsantsCohort StudiesHumansPPAR gammaRetrospective StudiesTranscriptional ActivationAnticonvulsantsPPAR gammaanti-epileptic drugsepilepsynext-generation RNA sequencingperoxisome proliferator-activated receptor γtype 2 diabetes mellitus

Identifiers

PMID37334286
PMCPMC10272786
OpenAlexW4379141768

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.