title: Epitope-restricted 65-kilodalton glutamic acid decarboxylase autoantibodies among new-onset Sardinian type 2 diabetes patients define phenotypes of autoimmune diabetes.
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 GAD65Ab-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 nondiabetic 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 GAD65Ab/IA-2Ab-positive patients (P < 0.01), and non-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.
authors.affiliation: Metabolic Disease Unit, Istituto di Clinica Medica, University of Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Maioli
authors.forename: Emilyn
authors.initials: E
authors.lastname: Alejandro
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tonolo
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Gilliam
authors.forename: Lynn
authors.initials: L
authors.lastname: Bekris
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hampe
authors.forename: Domenica A
authors.initials: DA
authors.lastname: Obinu
authors.forename: Alberto
authors.initials: A
authors.lastname: Manconi
authors.forename: Loreta
authors.initials: L
authors.lastname: Puddu
authors.forename: Kristian
authors.initials: K
authors.lastname: Lynch
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015992:Body Mass Index; D002096:C-Peptide / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D000939:Epitopes; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D000939:Epitopes; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2