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T-Cell Responses to Islet Antigens Improves Detection of Autoimmune Diabetes and Identifies Patients With More Severe ß-Cell Lesions in Phenotypic Type 2 Diabetes

From the Veterans Affairs Puget Sound Health Care System, Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington

Address correspondence and reprint requests to Barbara Brooks-Worrell, PhD, Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Building 1, Room 609, Seattle, WA 98108. E-mail: bbrooks{at}u.washington.edu

Abbreviations: Ab, autoantibody; IAA, insulin autoantibody; IA-2Ab, insulinoma-associated protein-2 autoantibody; ICA, islet cell autoantibody; IDS, Immunology of Diabetes Society; JDF, Juvenile Diabetes Foundation; LADA, latent autoimmune diabetes in adults; PBMC, peripheral blood mononuclear cell; SI, stimulation index

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 ß-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. ß-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 ß-cell lesion compared with Ab assessment alone.

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