A study of type-1 diabetes associated autoantibodies in schizophrenia

Abstract

Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.

Diabetic ketoacidosis and diabetes associated with antipsychotic exposure among a previously diabetes-naive population with schizophrenia: a nationwide nested case–control study

“…Correspondingly, the risk of type 2 diabetes associated with antipsychotic exposure was increased, thus corroborating the findings of a previous study Of the remaining six of 28 DKA cases, the aetiology could not be determined, as four were fatal within 8 days and two were not redeeming prescriptions for insulin and oral glucose-lowering agents a Including chlorpromazine, chlorprothixene, levomepromazine, melperone, pipamperone, sulpiride and thioridazine b Including loxapine, periciazine, perphenazine, prochlorperazine and zuclopenthixol c Including flupentixol, fluphenazine, haloperidol, penfluridol and pimozide [20]. While the risk of type 1 diabetes associated with antipsychotic exposure tended to be slightly increased, although insignificant, the risk of type 1 diabetes in the schizophrenia population is reduced [8][9][10][11]. Some type 2 diabetes cases and post-DKA type 2 diabetes cases initially received insulin and later switched to oral glucose-lowering agents, potentially reflecting the physician's judgement that the individual had either type 1 diabetes or ketosis-prone type 2 diabetes, where both insulin secretion and action are transitorily impaired [5].…”

“…Notably, the incidence of DKA in the population with schizophrenia exposed to antipsychotics is tenfold higher relative to the general population [7]. Conversely, although DKA occurs predominantly in connection with type 1 diabetes, there is a reduced risk of type 1 diabetes among individuals with schizophrenia [8][9][10][11].…”

Detection of circulating natural antibodies to inflammatory cytokines in type-2 diabetes and clinical significance

“…Five linear peptide antigens that are respectively derived from IL1α, IL1ß, IL6, IL8 and TNF-α, were designed according to the computational prediction of human leukocyte antigen (HLA) class II epitopes [ 23 , 24 ], and their amino acid sequences are given in Table 1 . An enzyme-linked immunosorbent assay (ELISA) was developed in-house based on a recent publication [ 25 ]. Briefly, solid-phase synthetic peptides were dissolved in 67 % acetic acid to obtain a concentration of 5mg/ml as stock solution.…”

Alteration of circulating natural antibodies against VEGFR1-derived peptide antigens in atherosclerosis

“…The sequence information of these five peptide antigens is shown in Table 2. Enzyme-linked immunosorbent assay (ELISA) was developed inhouse for detection of plasma IgG levels for the above three target molecules as described in previous reports [24,25]. In order to minimize the effect of non-specific binding on the accuracy of experimental data, the specific binding ratio (SBR) was used to represent a relative level of plasma IgG for CD25, FOXP3 and VEGFR1.…”