Metabolic Effects and Epilepsy Management in Diabetes

Epilepsy and diabetes are two chronic disorders whose coexistence poses unique challenges for clinical management and patient quality of life. Metabolic fluctuations intrinsic to diabetes, such as hyperglycaemia, hypoglycaemia and insulin resistance, directly influence neuronal excitability and seizure threshold. Conversely, recurrent seizures and certain anti-epileptic drugs may disrupt glucose homeostasis, exacerbate insulin resistance and alter lipid profiles. Emerging evidence highlights that energy-sensing pathways—including the adenosine monophosphate-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) cascades—play a pivotal role in both glycaemic control and neuronal survival. Antidiabetic agents such as metformin and dipeptidyl peptidase-4 inhibitors, along with dietary strategies like time-restricted feeding, have demonstrated antiseizure properties in preclinical and clinical settings. Integrating continuous glucose monitoring, personalised insulin regimens and metabolic adjuvants into epilepsy care offers the promise of reducing seizure burden, preventing cognitive decline and optimising long-term outcomes in patients with diabetes.

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Metabolic Effects and Epilepsy Management in Diabetes publication trend

The graph below shows the total number of articles in metabolic effects and epilepsy management in diabetes across all publications each year (not limited to Nature Index journals).

Technical terms

Hypoglycaemia: A state of abnormally low blood glucose that can provoke neuronal hyperexcitability and seizures.

AMPK: Adenosine monophosphate-activated protein kinase, a cellular energy sensor that regulates metabolic pathways and influences neuronal survival.

mTOR: Mechanistic target of rapamycin, a kinase governing cell growth and metabolism, whose dysregulation contributes to epileptogenesis.

PPARγ: Peroxisome proliferator-activated receptor gamma, a nuclear transcription factor that modulates glucose and lipid metabolism.

Kv4 channels: Subthreshold A-type potassium channels that shape neuronal repolarisation and control excitability.

DPP4: Dipeptidyl peptidase-4, an enzyme targeted by certain antidiabetic drugs, structurally related to accessory proteins regulating potassium channels.

References

1. 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. Frontiers in Endocrinology (2023).
2. New insights on the potential anti‐epileptic effect of metformin: Mechanistic pathway. Journal of Cellular and Molecular Medicine (2023).
3. Anticonvulsant Effect of Time-Restricted Feeding in a Pilocarpine-Induced Seizure Model: Metabolic and Epigenetic Implications. Frontiers in Cellular Neuroscience (2016).
4. Vildagliptin showed anti-epileptic effects and promoted subthreshold A-type potassium currents by regulating DPPs and Kv4s binding. Neuroscience Letters (2024).