Epilepsy in children with type 1 diabetes mellitus: Pathophysiological basis and clinical hallmarks

Mastrangelo, Mario; Tromba, Valeria; Silvestri, Francesca; Costantino, Francesco

doi:10.1016/j.ejpn.2018.12.006

Cited by 22 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite massive efforts and investments, our current insight into the mechanisms of epilepsy alone is still limited, and the underlying mechanisms of type 1 diabetes are still elusive in many aspects . The association between diabetes and epilepsy is most likely based on several different mechanisms . One potential route is through the autoimmune system, as epilepsy is a common comorbid disease in several autoimmune disorders .…”

Section: Discussionmentioning

confidence: 99%

“…While the coincidence of type 1 diabetes mellitus and epilepsy is being increasingly reported, so far, only two reports provide population‐based estimates of the coincidence of the two diseases . In a Taiwanese population study of patients ≤18 years of age followed up for 10 years by Chou et al, the cohort with type 1 diabetes was almost three times as likely to develop epilepsy as the control cohort.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland

et al. 2019

View full text Add to dashboard Cite

While the coincidence of type 1 diabetes mellitus and epilepsy is being increasingly reported, 1,2 so far, only two reports provide population-based estimates of the coincidence of the two diseases. 3,4 In a Taiwanese population study of patients ≤18 years of age followed up for 10 years by Chou et al, 3 the cohort with type 1 diabetes was almost three times as likely to develop epilepsy as the control cohort. However, the study had certain methodological problems. 5 In particular, the patients with diabetes and epilepsy included incident and prevalent cases of epilepsy, and therefore, the data were not applicable for the evaluation of epilepsy incidence. 5 The only other population-based study, reported from the UK by Dafoulas et al, 4 also gave an over threefold excess Abstract Aim: The aim was to determine temporal changes in increased risk of epilepsy among children with type 1 diabetes. Methods:The incidence of epilepsy up to age 15 in children with prior type 1 diabetes was analysed regarding the general Finnish child population using data from the Finnish nationwide hospital register. Type 1 diabetes and epilepsy were identified by the International Classification of Diseases 9th and 10th revision codes. Epilepsy was defined according to ILAE guidelines. The analyses were done using negative binomial regression models.Results: Preceding type 1 diabetes was diagnosed in 6162 (0.91%) of the 679 375 general children population. Incidence rate of new-onset epilepsy among children with type 1 diabetes was higher than in controls (140 vs 82 per 100 000 personyears at risk, respectively). The excess incidence diminished with time (P = 0.033 for diabetes to birth cohort interaction), from over twofold in birth cohort [1990][1991][1992][1993] [incidence rate ratio 2.2 (95% CI 1.7-2.9)] to 40% in birth cohort 1998-2000 [1.4 (95% CI 1.001-1.9)]. Conclusion:In a population study setting, children with type 1 diabetes had an increased, but slowly declining risk of developing epilepsy. Future research may elucidate the underlying mechanisms. K E Y W O R D Schildhood seizures, comorbidity, incidence of epilepsy, register study, type 1 diabetes

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland

et al. 2019

View full text Add to dashboard Cite

show abstract

“…A disorder of particular interest is diabetes [6][7][8][9]. The connection between epilepsy and type 1 diabetes mellitus (T1DM) has already been highlighted [10][11][12][13][14][15][16][17][18][19][20]. A recent meta-analysis found that people with T1DM have a 2 to 6 fold increased risk of epilepsy than the general population [20].…”

Section: Introductionmentioning

confidence: 99%

“…A recent meta-analysis found that people with T1DM have a 2 to 6 fold increased risk of epilepsy than the general population [20]. The onset of T1DM precedes the onset of epilepsy by a mean period of 1.5-2.8 years [20].…”

Section: Introductionmentioning

confidence: 99%

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

Shlobin

Sander

2020

Epilepsy & Behavior

View full text Add to dashboard Cite

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 3,361 articles, of which 82 were included in the scoping review. We reviewed articles with a focus on the association of epilepsy and T2DM, drivers, and biological mechanisms. 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 due to lack of exercise and the effects of some antiseizure medications, which makes them susceptible to T2DM due to 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 antiseizure medications. Future research involving a combined genetic and molecular pathway approach will likely yield valuable insight regarding the comorbidity of epilepsy and T2DM.

show abstract

“…So far, no definitive genetic predisposition has been identified. Promising candidate genes involve those encoding for enzymes of glucose metabolism and proteins of major histocompatibility complex [13].…”

Section: Discussionmentioning

confidence: 99%

Association between high titers of glutamic acid decarboxylase antibody and epilepsy in patients with type 1 diabetes mellitus: A cross-sectional study

Aguiar

Dantas

Cabral

et al. 2019

Seizure

View full text Add to dashboard Cite

Individuals with type 1 diabetes mellitus (T1D) are at higher risk of epilepsy. T1D is a progressive immune-mediated disease and the etiology of epilepsy remains unknown in most. Glutamic acid decarboxylase (GAD) catalyzes GABA formation. GABA-secreting neurons and pancreatic beta cells are the major cells expressing GAD. Methods: Cross-sectional study. Patients with T1D from a multiethnic population underwent GADA measurement to investigate possible association between T1D and epilepsy of unknown etiology. Results: T1D patients were analyzed (n = 375). Overall frequency of epilepsy was 5.9% (n = 22). Frequency of epilepsy of unknown etiology was 3.2% (n = 12). Of these, 8 (2.1%) had idiopathic generalized epilepsy (IGE) and 4 (1.1%) MRI-negative temporal lobe epilepsy (TLE). Patients with T1D and epilepsy of unknown etiology did not show differences in GADA frequency (83.3% vs 50%; p = 0.076); however, their titers were higher (106.9 ± 136.5 IU/mL; median 7; IQR 1.65-256 vs 10.2 ± 14.5 IU/ml; median 4.3; IQR 1.9-8.9; p = 0.019) compared to patients without epilepsy. Moreover, epilepsy of unknown etiology was associated with GADA titers ≥ 100 UI/mL [odds ratio (OR) 4.42, 95% CI 2.36-8.66]. Conclusion: Epilepsy frequency was elevated in patients with T1D and multiethnic background. Presence of epilepsy of unknown etiology was associated with high titers of GADA in this population with long-standing T1D, which has different ethnic and genetic background compared to previous studies. Further prospective studies are required to identify if GADA presence or its persistence are directly responsible for epilepsy in individuals with T1D.

show abstract

Epilepsy in children with type 1 diabetes mellitus: Pathophysiological basis and clinical hallmarks

Cited by 22 publications

References 29 publications

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland

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

Association between high titers of glutamic acid decarboxylase antibody and epilepsy in patients with type 1 diabetes mellitus: A cross-sectional study

Contact Info

Product

Resources

About