Measuring Islet autoantibodies: When, why and how?

Abstract

Islet autoantibodies are central biomarkers of pancreatic beta-cell autoimmunity and have transformed the classification and prediction of autoimmune diabetes. Since the first description of islet cell cytoplasmic autoantibodies (ICA), testing has evolved toward more specific markers, including insulin autoantibodies (IAA), glutamic acid decarboxylase autoantibodies (GADA), insulinoma-associated antigen-2 autoantibodies (IA-2A), and zinc transporter 8 autoantibodies (ZnT8A). These autoantibodies are not considered directly pathogenic, but their presence provides objective evidence of an autoimmune process directed against pancreatic beta cells. In Bangladeshi young-onset diabetes, our group (the Study on Diabetes and Obesity in Young; SODY) has observed considerable clinical overlap between autoimmune and non-autoimmune phenotypes. In a pilot tertiary-centre study, GADA positivity was more frequent than ZnT8A positivity, while antibody-positive and antibody-negative participants were not clearly separable by routine phenotypic variables. In another cohort of newly diagnosed phenotypically T2D, GADA positivity was detected in a meaningful subgroup and was associated with lower beta-cell function and higher fasting plasma glucose. These findings emphasize that clinical features, C-peptide, insulin, or proinsulin levels alone may not always distinguish diabetes subtypes. Islet autoantibody testing is therefore most useful in newly diagnosed or atypical diabetes, suspected autoimmune diabetes, adult-onset diabetes with uncertain classification, and selected high-risk individuals. A recent study by the SODY group also suggests that manufacturer-recommended thresholds may not always be directly transferable, supporting context-specific interpretation. Islet autoantibody testing should be used selectively and integrated with clinical and metabolic assessment.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S19]