title: Impact of islet autoimmunity on the progressive β-cell functional decline in type 2 diabetes.
abstract: OBJECTIVE
  Cross-sectional studies have suggested that islet autoimmunity may be more prevalent in type 2 diabetes (T2D) than previously appreciated and may contribute to the progressive decline in β-cell function. In this study, we longitudinally evaluated the effect of islet autoimmune development on the progressive β-cell dysfunction in T2D patients.
  
  
  METHODS
  Twenty-three T2D patients negative for islet autoantibodies (GAD antibody and insulinoma-associated protein 2) and islet-specific T cells were evaluated prospectively for up to 36 months. We investigated the percentage of patients who developed islet autoantibodies (Ab+) and/or islet-reactive T cells (T+) and the effect of the islet autoimmunity on fasting and glucagon-stimulated C-peptide responses. We defined positive islet autoimmunity as Ab+ and/or T+ for at least two study visits.
  
  
  RESULTS
  Of the 23 patients, 6 (26%) remained negative for islet autoimmunity (Ab-T-), 14 (61%) developed Ab+ and/or T+, and 3 (13%) were unclassifiable because they developed islet autoimmunity at only one study visit. Islet Ab+ was observed to be less stable than islet-specific T-cell responses. Development of islet autoimmunity was significantly associated with a more rapid decline in fasting (P < 0.0001) and glucagon-stimulated (P < 0.05) C-peptide responses.
  
  
  CONCLUSIONS
  These pilot data suggest that the development of islet autoimmunity in T2D is associated with a significantly more rapid β-cell functional decline.
authors.affiliation: VA Puget Sound Health Care System, Seattle, WA, and Department of Medicine, University of Washington, Seattle, WA bbrooks@u.washington.edu.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Brooks-Worrell
authors.affiliation: VA Puget Sound Health Care System, Seattle, WA, and Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Boyko
authors.affiliation: VA Puget Sound Health Care System, Seattle, WA, and Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000009:adverse effects; D015551:Autoimmunity; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1