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.

BackgroundA dysregulation in the metabolism of lipids may be an early marker of autoimmunity in Type 1 Diabetes (T1D). It would be of general importance to identify metabolic patterns that would predict the risk for T1D later in life. The aim of this study was to perform a prospective evaluation of glutamine and phospholipids levels in Brazilian first degree relatives (FDR) of patients with T1D in a mean interval of 5 years.FindingsBrazilian FDR (n = 30) of patients with T1D were evaluated and blood was sampled to measure the levels of glutamine and phospholipids in the fasting serum by quantitative colorimetric method. The tests were repeated after a mean interval of 5 years and compared to a control group (n = 20). The FDR presented lower levels of phospholipids than controls (p = 0.028), but not of glutamine (p = 0.075). Phospholipids levels decreased over time (p = 0.028) in FDR and were associated with Glutamic acid decarboxylase autoantibody (GADA) titers (p = 0.045), autoantibody positivity (p = 0.008) and PTPN22 polymorphisms (p = 0.014).ConclusionsIn this Brazilian multiethnic population, there was a significant decrease in phospholipids levels in FDR in patients with T1D during a 5-year prospective follow-up, as well as a significant association between these metabolite, GADA and PTPN22 polymorphisms. For Glutamine no difference was found. These findings suggest that a dysregulation in the metabolism of lipids may precede the onset of the autoimmunity in T1D.