Objective: Disease-associated T-cell autoreactivities are seen in most type 1 diabetic patients and are thought to emerge before islet autoantibodies, but host factors that impact autoimmune elements remain uncertain. We assessed if adiposity and measures of insulin sensitivity impact T- and B-cell autoimmunity in children with insulin-requiring diabetes.
Research design and methods: Insulin-requiring children and adolescents diagnosed between January 2004 and June 2008 were studied (n = 261): age 9.7 ± 4 years, 92% white, and 60% male. T-cell responses to 10 diabetes-associated antigens, β-cell autoantibodies (GADA, IA-2A, IAA, and ICA), BMI z score (BMIz), and waist percentile were measured at onset and 3 months later.
Results: All but one subject had either T- or B-cell autoimmunity. Diabetes-associated T-cell autoreactivities were found in 92% of subjects. Higher amplitude T-cell autoreactivities to neuronal diabetes-associated autoantigens were seen in those with the highest BMIz quintile, BMI ≥85th percentile (P < 0.05), and waist circumference ≥85th percentile (P < 0.05). There were no relationships between the number of T-cell reactivities or T-cell diversity with adiposity measures or autoantibody number or type. Patients with positive T-cell reactivities but without autoantibodies had the highest BMIz (P = 0.006).
Conclusions: Our observations link obesity and diabetes-related autoimmunity, suggesting an amplification of neuronal T-cell autoimmunity associated with adiposity and/or insulin resistance, with obesity-related inflammation possibly enhancing islet autoimmunity.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.