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

Department of Medicine , University of Washington Seattle, Seattle, Washington, United States
Diabetes (Impact Factor: 8.1). 09/2007; 56(8):2110-5. DOI: 10.2337/db06-0552
Source: PubMed


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.

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    • "We have been investigating T cell responses in classic T1D and in adult phenotypic T2D patients and have identified T cell responses to islet proteins (Brooks-Worrell et al., 1996, 1999, 2001, 2004). Moreover, we (Goel et al., 2007) have also demonstrated a correlation between T cell positivity and diminished beta cell function. Our data demonstrate that identifying patients with diabetes who have T cell responses to islet proteins identifies the patients with a more severe beta cell lesion compared with autoantibody assessment alone. "
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