Impact of Islet Autoimmunity on the Progressive β-Cell Functional Decline in Type 2 Diabetes

• DOI: 10.2337/dc14-0961
• Publication Date: 2014-09-20T05:13:32Z
• Authors: Barbara M. Brooks...; Edward J. Boyko; Jerry P. Palmer
• Keywords: Adult; Male; 0301 basic medicine; Glutamate Decarboxylase; T-Lymphocytes; Autoimmunity; Pilot Projects; Middle Aged; 3. Good health; 03 medical and health sciences; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Insulin-Secreting Cells; Humans; Female; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Pathophysiology/Complications; Autoantibodies; Follow-Up Studies

OBJECTIVECross-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.RESEARCH DESIGN AND METHODSTwenty-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.RESULTSOf 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.CONCLUSIONSThese pilot data suggest that the development of islet autoimmunity in T2D is associated with a significantly more rapid β-cell functional decline.