Epitope-restricted 65-kilodalton glutamic acid decarboxylase autoantibodies among new-onset sardinian type 2 diabetes patients define phenotypes of autoimmune diabetes

Mario Maioli, Emilyn Alejandro, Giancarlo Tonolo, Lisa K. Gilliam, Lynn Bekris, Christiane S. Hampe, Domenica A. Obinu, Alberto Manconi, Loreta Puddu, Kristian Lynch, Åke Lernmark

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The 65-kDa glutamic acid decarboxylase (GAD65) autoantibodies (GAD65Abs), commonly found in type 1 diabetes mellitus (T1DM) patients, are also found at lower frequencies in type 2 diabetes mellitus (T2DM) patients. GAD65Abs in T1DM patients are epitope specific, in contrast to those found in other GAB65Ab-positive individuals, including T2DM patients. Our aim was to assess whether epitope-specific GAD65Abs, or the additional presence of islet antigen 2 (IA-2) autoantibodies, better define T1DM phenotypes among T2DM patients. GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 non-diabetic patient controls. Autoantibody binding specificity to the N-terminal, middle (M), and C-terminal (C) portions of the GAD65 molecule was evaluated. Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. GAD65Ab-positive T2DM patients with M+C (epitope-specific) reactivity were found to have the lowest body mass index (P < 0.001), followed by GAB65Ab/LA-2Ab-positive patients (P < 0.01), andnon-M+C-reactive (non-epitope-specific) patients (P < 0.02). In GAD65Ab-positive T2DM patients, c-peptide levels were lower in M+C-reactive compared with non-M+C-reactive patients. Sardinian T2DM patients with M+C-predominant GAD65Ab reactivity have clinical features more similar to those of T1DM patients. Thus, GAD65Ab epitope analysis may help to define T1DM phenotypes among newly diagnosed GAD65Ab-positive patients classified with T2DM.

Original languageEnglish (US)
Pages (from-to)5675-5682
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number11
DOIs
StatePublished - Nov 2004

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