Identification of Autoantibody-Negative Autoimmune Type 2 Diabetic Patients

OBJECTIVE: Islet autoimmunity has long been recognized in the pathogenesis of type 1 diabetes and is becoming increasingly acknowledged as a component in the pathogenesis of type 2 diabetes. Islet reactive T cells and autoantibodies have been demonstrated in type 1 diabetes, whereas islet autoimmunity in type 2 diabetes has been limited to islet autoantibodies. In this study, we investigated whether islet reactive T cells might also be present in type 2 diabetic patients and how islet reactive T cells correlate with β-cell function. RESEARCH DESIGN AND METHODS: Adult phenotypic type 2 diabetic patients (n = 36) were screened for islet reactive T-cell responses using cellular immunoblotting and five islet autoantibodies (islet cell antibody, GADA, insulin autoantibody, insulinoma-associated protein-2 autoantibody, and zinc transporter autoantibody). RESULTS: We identified four subgroups of adult phenotypic type 2 diabetic patients based on their immunological status (Ab⁻T⁻, Ab⁺T⁻, Ab⁻T⁺, and Ab⁺T⁺). The Ab⁻T⁺ type 2 diabetic patients demonstrated T-cell responses similar to those of the Ab⁺T⁺ type 2 diabetic patients. Data were adjusted for BMI, insulin resistance, and duration of diabetes. Significant differences (P < 0.02) were observed among groups for fasting and glucagon-stimulated C-peptide responses. T-cell responses to islet proteins were also demonstrated to fluctuate less than autoantibody responses. CONCLUSIONS: We have identified a group of adult autoimmune phenotypic type 2 diabetic patients who are Ab⁻T⁺ and thus would not be detected using autoantibody testing alone. We conclude that islet autoimmunity may be more prevalent in adult phenotypic type 2 diabetic patients than previously estimated.