Combined Detection of Islet Autoantibodies for Clinical Diagnosis of Type 1 Diabetes in the Low-Prevalence Population

Abstract

Context: Single positive islet autoantibodies (IAbs), sometimes detected in healthy individuals and patients with low-risk of developing type 1 diabetes (T1D), are considered to be irrelevant to the development of diabetes, making it difficult to diagnose and classify adult-onset diabetes.

Objective: To determine the significance and clinical value of IAbs in T1D diagnosis in the low-prevalence population, and to explore whether an electrochemiluminescence IAb detection assay can improve the clinical utility of IAbs in the immunodiagnosis of T1D in the low-prevalence population.

Methods: A total of 633 newly diagnosed patients with adult-onset diabetes (≥18 years old) were divided into 2 groups according to their clinical phenotypes: 575 patients with age at diagnosis ≥35 years and body mass index (BMI) ≥ 24 kg/m2 were considered a low-prevalence population (population with a low prevalence of T1D) and the other 58 patients were considered a high-prevalence population. All the samples from 633 participants were tested with IAbs using standard radiobinding assays (RBAs) and electrochemiluminescence (ECL) assays in parallel.

Results: Compared with the high-prevalence population, fewer positive IAbs (94/575, 16.3% vs 28/58, 48.3%) were detected in the low-prevalence population, and more of whom (69/94, 73.4% vs 9/28, 32.2%) were positive for a single IAb, with glutamate decarboxylase antibodies being the most prevalent single IAb. Single-IAb detection in the low-prevalence population did not always suggest the T1D phenotype. Combined detection of IAbs by RBA and ECL assay had a significant clinical utility to distinguish autoimmune diabetes in the low-prevalence population with low BMI, poor β-cell function at the diagnosis, and an accelerated decline in β-cell function during the follow-up.

Conclusion: Combined autoantibody detection by RBA and ECL assays improved differentiating autoimmune from nonautoimmune diabetes in the low-prevalence population.

Keywords: body mass index (BMI); electrochemiluminescence (ECL) assay; islet autoantibodies (IAbs); radiobinding assay (RBA); type 1 diabetes (T1D).