Enhancing the Understanding of Pre-Type 1 Diabetes in the General Population

Abstract

Type 1 diabetes occurs in ∼90% of patients with no family history of the disease. The majority of studies seeking to identify at-risk subjects have been conducted in first-degree relatives who comprise just 10% of all cases of type 1 diabetes but may have a 20-fold increased risk for type 1 diabetes (1). Although the peak incidence occurs at adolescence, there are data to suggest that 5–10% of all adults diagnosed with type 2 diabetes may actually have type 1 diabetes (latent autoimmune diabetes in adults [LADA]). If type 1 diabetes is to be prevented, significantly enhanced understanding of both the mechanisms leading to type 1 diabetes and the natural history of the pre-diabetic period is essential. Current evidence suggests that type 1 diabetes results from a complex interaction between type 1 diabetes genetic susceptibility (predominantly HLA Class II associations) and environmental exposure(s) leading to a breakdown of tolerance culminating in β-cell autoimmunity and destruction (2). In the process leading to overt type 1 diabetes, both T and B lymphocytes are activated. B-lymphocyte activation is characterized by the emergence of cytoplasmic islet cell autoantibodies (ICAs) and one or more autoantibodies against the β-cell–specific autoantigen insulin, glutamate decarboxylase, the IA-2 protein tyrosine phosphatase, or the zinc transporter ZnT8 (IAA, GADA, IA-2A, and ZnT8A, respectively). For the most part, IAA, GADA, IA-2A, and ZnT8A have replaced ICA, which is measured using indirect immunofluorescence that requires a subjective evaluation of the fluorescence intensity. The IAA, GADA, IA-2A, and ZnT8A analyses require only small amounts of serum (5–20 μl in most assays) and are thus well suited for large-scale studies comprising both infants and small children. Serum samples can be safely stored at −20°C for years before the measurement of the autoantibodies is undertaken, and the samples usually also tolerate repeated freeze-thaw cycles without …