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

• DOI: 10.2337/db06-0552
• Publication Date: 2007-07-27T17:34:04Z
• Authors: Amit Goel; Harvey Chiu; Jamie Felton; Jerry P. Palmer; Barbara Brooks-Wo...
• Keywords: Adult; Male; C-Peptide; T-Lymphocytes; Fasting; Middle Aged; Glucagon; 3. Good health; Islets of Langerhans; 03 medical and health sciences; Diabetes Mellitus, Type 1; Glucose; Phenotype; 0302 clinical medicine; Diabetes Mellitus, Type 2; Humans; Female; Antigens; Aged; Autoantibodies; Cell Proliferation

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