A population-based study of epilepsy incidence in association with type 2 diabetes and severe hypoglycaemia

doi:10.1016/j.diabres.2018.03.020

Diabetes Research and Clinical Practice

Volume 140, June 2018, Pages 97-106

https://doi.org/10.1016/j.diabres.2018.03.020 Get rights and content

Abstract

Aims

This study was conducted to investigate potential link between type 2 diabetes mellitus (T2DM) and epilepsy, and the role of severe hypoglycaemia (SH) might play in the relationship.

Methods

This was a cohort study based on Taiwan’s National Health insurance claims. Totally 751,792 people with T2DM and 824,253 matched controls were identified in 2002–2003 and followed to incidence of epilepsy or end of 2011. We used Cox proportional hazard model to relate epilepsy incidence to separate and joint effects of T2DM and SH. A possible mediation effect of SH on the association between T2DM and epilepsy was analyzed.

Results

Over a 10-year follow-up, patients with T2DM had a higher incidence rate of epilepsy than controls (35.0 vs 21.9 per 10,000 person-years). After controlling for potential confounders including SH, T2DM increased the hazard of epilepsy by some 50%. The stratified analysis further indicated that T2DM (hazard ratio (HR)=1.44, 95% confidence interval (CI) = 1.40–1.47), and SH (HR = 2.22, 95% CI = 1.76–2.81) were both independent risk factors for epilepsy. SH did not modify but mediated 12% of the association between T2DM and epilepsy.

Conclusion

Our findings supported that SH may increase the risk of epilepsy, and that T2DM may increase risk of epilepsy independent of SH.

Introduction

Type 2 diabetes has been found to be associated with increased risks of various neurological disorders, including dementia [1], Parkinson’s disease [2], [3], and possibly multiple sclerosis [4]. Recent studies have found that type 1 diabetes could be associated with the incidence of epilepsy, though the underlying mechanisms exactly linking such a relationship remain unclear [5]. Previous studies noted that epilepsy or seizures are associated with various autoimmune or inflammatory disorders and are involved in the pro-inflammatory processes [6], [7]. Additionally, metabolic abnormalities of diabetes, such as hyperglycaemia and hypoglycaemia, may pose adverse effects on the central nervous system [5], thereby leading to seizure. It has been well documented that both hyperglycaemia and hypoglycaemia commonly occur in people with diabetes can alter the balance between the inhibition and excitation of neuronal networks and cause focal motor seizures [8], [9].

Epilepsy is a group of neurological diseases characterized by epileptic seizures. Mortality in people with epilepsy exceeds that in the general population, which is especially true for certain causes of death, including cerebrovascular disease (CVD), neoplastic disorders, and accidents [10]. In addition to some known risk factors for epilepsy including degenerative brain disorders and head injuries [11], several diseases associated with type 2 diabetes such as stroke and dementia have also been considered as predisposing factors to epilepsy [12].

Evidence concerning the association of diabetes with epilepsy was mainly derived from studies of type 1 diabetes [13], [14], [15]; little is known about the risk of epilepsy in association with type 2 diabetes. People with type 2 diabetes are also vulnerable to the occurrence of hypoglycaemia and some disorders that co-morbid epilepsy. While severe hypoglycaemia can lead to seizure, coma, and is even life-threatened in a relatively short period, some of the hypoglycaemia-induced changes in electrical activity may persist for a long period of time [16].

We conducted this population-based study to estimate the incidence of epilepsy in patients with type 2 diabetes, with particular interest in assessing whether severe hypoglycaemia may modify or mediate the association of type 2 diabetes with epilepsy incidence.

Section snippets

Data source

The study proposal was approved by the Institutional Review Board of National Cheng Kung University Hospital (A-EX-104-008). Data were retrieved from Taiwan’s NHI research database, a medical claim database that stores the medical records of beneficiaries that are uploaded by medical institutions to obtain reimbursement from NHI. Taiwan’s NHI program universally covers medical insurance for nearly all (>97%) Taiwanese citizens (prisoners and military personnel were exempted in our study period)

Results

Patients with type 2 diabetes and control subjects enrolled in this study are comparable with respect to age, sex, insurance premium, level of urbanization, and family income level. Prevalence rates of certain co-morbidities, including neurotic-anxiety disorder, sleep disorder, cerebral palsy, and cerebral vascular disorder were higher in type 2 diabetes than in controls. Patients with type 2 diabetes also had a higher frequency of ambulatory care visits than controls (Table 1). It shows that

Discussion

To our knowledge, this is the first population-based study reporting an elevated risk of epilepsy in patients with type 2 diabetes. Numerous studies have found that children and adolescents with type 1 diabetes were associated with three times higher incidence [13], [14] and 2–6-fold prevalence of epilepsy [15], [28] as compared to the general population. The possible mechanisms were reportedly involved in the common associations of type 1 diabetes and epilepsy with anti-glutamic acid

Acknowledgements

This study is based in part on data from the NHIRD provided by the National Health Insurance Administration, Ministry of Health and Welfare of Taiwan, and managed by the National Health Research Institutes. The interpretation and conclusions contained herein do not represent the views of the National Health Insurance Administration, Ministry of Health and Welfare of Taiwan or National Health Research Institutes.

Funding information

This study was supported by a grant from the Ministry of Science and Technology (

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Data regarding the comorbid association of epilepsy and type 2 diabetes mellitus (T2DM) are sparser but exist. A cohort study of national health insurance claims in Taiwan found that people with T2DM had a higher incidence of epilepsy than controls independent of severe hypoglycemia [21]. A Bosnian retrospective study found an association of early and late seizures with T2DM after stroke [22].
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.
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It is clear great health related benefits have been achieved by feeding the ketogenic to individuals subject to seizures where it helps manage the malaise. Sports applications are evident to. Glucose control diets provide health benefits of the ketogenic diet potentially and there is some evidence they are/can be very effective.
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A population-based study of epilepsy incidence in association with type 2 diabetes and severe hypoglycaemia

Abstract

Aims

Methods

Results

Conclusion

Introduction

Section snippets

Data source

Results

Discussion

Acknowledgements

Funding information

J Epidemiol

Seizure

Lancet Neurol

Seizure

Kidney Int

Type 2 diabetes as a risk factor for dementia in women compared with Men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia

Diabetes Care

Diabetes and the risk of developing Parkinson’s disease in Denmark

Diabetes Care

Risk of Parkinson disease onset in patients with diabetes: a 9-year population-based cohort study with age and sex stratifications

Diabetes Care

Association between diabetes, severe hypoglycemia, and electroencephalographic abnormalities

Arch Dis Child

Autoantibodies in the patient with drug-resistant epilepsy: are we missing a treatable etiology?

Arch Neurol

Diabetes and epilepsy in children and adolescents

Curr Diab Rep

Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitro

Eur J Neurosci

Severe hypoglycaemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality

PLoS ONE

Epilepsy in cerebrovascular diseases: review of experimental and clinical data with meta-analysis of risk factors

Epilepsia

Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study

Diabetologia

Type 1 diabetes mellitus and risk of incident epilepsy: a population-based, open-cohort study

Diabetologia

Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications

Nat Rev Endocrinol