The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients

Abstract

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.autoantibodies, heterogeneity, islet failure, type 1 diabetes Citation:

High Prevalence of a Monogenic Cause in Han Chinese Diagnosed With Type 1 Diabetes, Partly Driven by Nonsyndromic Recessive WFS1 Mutations

“…T1Dclin case subjects were tested for autoantibodies against GAD (GADA), islet antigen 2 (IA-2A), and ZnT8 (ZnT8A) by radioimmunoassay (12). Case subjects negative for all three were excluded from the GWAS and recruited for our project.…”

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

“…Autoantibodies to ZnT8, GAD65, and IA-2 were detected separately using protein A radio-binding assays ( 1 ). Serum IAA was only tested within two weeks after diagnosis using an ELISA kit (Biomerica, USA) to avoid interference of injected insulin.…”

“…Type 1 diabetes (T1D) is an autoimmune disease involving insulin-producing pancreatic islet beta cell prolonged destruction by autoreactive effector T lymphocytes ( 1 ). Although management with exogenous insulin changes T1D from an acutely fatal disease into a chronic disease, achieving glycemic control is still subject to significant limitations ( 2 ).…”

Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody

“…389 GD blood samples and 334 HT blood sample taken into the plain tubes, which were drawn at the patients' enrollment, were centrifuged at 350×g and serum was stored frozen at −80°C for 6.36 ± 6.34 months for detecting islet autoantibodies. Serum islet autoantibodies were measured by radioligand binding assay as previously described 26,27 , using 35 S-labeled glutamic acid decarboxylase-65 (GAD65), protein-tyrosine-phosphatase-2 (IA-2) and zinc transporter 8 (ZnT8). The plasmid containing the complementary DNA for cytoplasmic carboxy-terminal domains (amino acid 268-369) of human ZnT8 carrying 325Arg (designated as CR) or a hybrid construct of the CR and 325Trp (CW; designated as CW-CR) with a CLFCEDPCDPSTPPGSSqGGGKDFSILLME hinge junction was generated.…”