Vitamin D deficiency and long-term risk of epilepsy or seizure in type 2 diabetes: a multicenter real-world cohort study.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of seizures and epilepsy; however, clinically measurable factors contributing to this risk remain unclear. Given the high prevalence of vitamin D deficiency (VDD) in T2DM and its potential effects on neuronal excitability, this study aimed to investigate the association between VDD and the long-term risk of incident epilepsy or seizure in adults with T2DM. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Global Collaborative Network. Adults with T2DM and a recorded 25-hydroxyvitamin D measurement between 2013 and 2023 were classified as having VDD (<20 ng/mL) or normal vitamin D levels (≥30 ng/mL). The primary outcome was incident epilepsy or seizure during an analytic window extending up to 12 years after the index date. The secondary outcomes included epilepsy subtypes, antiepileptic medication use, and all-cause mortality. Results: After matching, 135,329 patients were included in each cohort. VDD was associated with a higher risk of incident epilepsy or seizure than normal vitamin D status (1.10% vs. 0.78%; HR, 1.37; 95% CI, 1.26-1.48; Conclusion: Among adults with T2DM, VDD was associated with a higher long-term risk of incident epilepsy or seizure, particularly intractable epilepsy. These findings suggest that VDD may serve as a clinically relevant risk marker; however, they do not establish causality or demonstrate that vitamin D supplementation prevents epilepsy or seizure.