Drivers for the comorbidity of type 2 diabetes mellitus and epilepsy: A scoping review

Epilepsy, a common neurologic condition, is associated with a greater prevalence of type 2 diabetes mellitus (T2DM). We examined potential drivers for the comorbidity of epilepsy and T2DM in an attempt to elucidate possible biological mechanisms underlying the development of processes in individuals. We searched PubMed and Medline up to December 2019. Our search yielded 3361 articles, of which 82 were included in the scoping review. We reviewed articles focusing on the association of epilepsy and T2DM, drivers, and biological mechanisms. We found that epilepsy is associated with obesity and obesity is associated with T2DM. Treatment with valproate (either sodium or acid) is associated with weight increase and hyperinsulinemia, while topiramate causes weight loss. People with epilepsy are less likely to exercise, which is protective against obesity. Mitochondrial dysfunction and adiponectin deficiency are common to epilepsy and T2DM. One possible mechanism for the comorbidity is mitochondrial dysfunction and adiponectin deficiency, which promotes epilepsy, obesity, and T2DM. Another possible mechanism is that people with epilepsy are more likely to be obese because of the lack of exercise and the effects of some antiseizure medications (ASMs), which makes them susceptible to T2DM because of the development of mitochondrial dysfunction and adiponectin deficiency. A third mechanism is that people with epilepsy have greater mitochondrial dysfunction and lower adiponectin levels than people without epilepsy at baseline, which may exacerbate after treatment with ASMs. Future research involving a combined genetic and molecular pathway approach will likely yield valuable insight regarding the comorbidity of epilepsy and T2DM.