The Interplay of Autoimmunity and Insulin Resistance in Type 1 Diabetes

Type 1 diabetes (T1D) is a common chronic disease characterized by selective autoimmune destruction of the pancreatic islet beta cells and subsequent dependence on exogenous insulin. Certain alleles including the high-risk HLA genotype, HLA-DR3-DQ2/DR4-DQ8, place individuals at increased risk of developing T1D. Autoantibodies to beta cell antigens are used in the diagnosis of T1D, and studies have shown that they can be used to predict risk of developing T1D in first degree relatives of probands. The annual global incidence of T1D is increasing by 3-5% per year. Many environmental factors have been implicated in the rising incidence of T1D. Proponents of the accelerator hypothesis argue that T1D and type 2 diabetes (T2D) are the same disorder of insulin resistance, although with different genetic backgrounds. While insulin resistance is a recognized hallmark of T2D, it also appears to play a significant role in the pathogenesis of T1D and its vascular complications. In this article, we will review: 1) immunogenetics of T1D, 2) risk factors for the development of islet autoimmunity and T1D, 3) mechanisms of insulin resistance in T1D, and 4) links between insulin resistance and complications in T1D. Further studies are needed to define environmental factors causing T1D as well as the role of insulin resistance in the pathogenesis of T1D and its complications. [Discovery Medicine 13(69):115-122, February 2012]