title: T-cell responses to islet antigens improves detection of autoimmune diabetes and identifies patients with more severe beta-cell lesions in phenotypic type 2 diabetes.
abstract: Latent autoimmune diabetes in adults or type 1.5 diabetes is considered to be a T-cell-mediated autoimmune disease. However, identification of patients is based commonly on autoantibody (Ab) detection. To determine whether measuring T-cell reactivity to islet proteins compared with measuring Abs improves detection of autoimmune diabetes and how beta-cell function correlates with T-cell reactivity compared with Ab positivity, we assessed the T-cell proliferative responses and Ab responses (islet cell autoantibodies, insulin autoantibodies, insulinoma-associated protein-2 autoantibodies, and GAD Abs) to islet proteins of 36 phenotypic type 2 diabetic patients. To be considered Ab(+) or T-cell(+), patients were required to be positive for a minimum of two consecutive time points. beta-Cell function was measured with fasting and glucagon-stimulated C-peptide. Independent of T-cell reactivity, Ab(+) and Ab(-) patients had comparable fasting and glucagon-stimulated C-peptide. Independent of Ab status, T-cell(+) patients demonstrated significantly lower glucagon-stimulated (P < 0.003) C-peptide compared with T-cell(-) patients. These data suggest that measuring T-cell responses to multiple islet proteins in phenotypic type 2 diabetic patients improves identification of patients with autoimmune diabetes and delineates those who have a more severe beta-cell lesion compared with Ab assessment alone.
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98108, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Goel
authors.forename: Harvey
authors.initials: H
authors.lastname: Chiu
authors.forename: Jamie
authors.initials: J
authors.lastname: Felton
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
authors.forename: Barbara
authors.initials: B
authors.lastname: Brooks-Worrell
mesh_terms: D000328:Adult; D000368:Aged; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D002096:C-Peptide / Q000097:blood; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000941:Antigens; D001323:Autoantibodies; D002096:C-Peptide; D005934:Glucagon; D005947:Glucose