Delving Into the Type 1 Diabetic Islet: Evidence That B-Cell Infiltration of Islets Is Linked to Local Hyperimmunity and Accelerated Progression to Disease

The incidence of type 1 diabetes is increasing, particularly in young children. Multicenter studies across Europe have shown a 5.4% annual rise in type 1 diabetes in children under the age of 5 years (1), increasing the burden on health care resources worldwide. Better understanding of the causes of this increase is required for new therapies or lifestyle changes to reverse this trend. The study by Leete et al. (2) in this issue of Diabetes demonstrates striking differences in the cellular composition of islet inflammation causing type 1 diabetes between children diagnosed before the age of 6 years and those developing disease at an older age that may help define mechanisms underlying accelerated progression to diabetes. The distinguishing feature of islet inflammation in very young children is a high proportion of infiltrating B lymphocytes. B-cell responses to islet autoantigens are characteristic of type 1 diabetes, and autoantibodies provide important predictive markers of disease. Studies in families of patients with diabetes have shown that autoantibodies first appear in the first 5 years of life, most commonly with specificity for insulin (3), which may then be followed by the progressive appearance of autoantibodies to other major islet cell antigens including glutamate decarboxylase (GAD), IA-2, and the zinc transporter ZnT8 (4). Diversification of the immune response appears critical for disease progression: few individuals persistently positive for …