Connecting Type 1 and Type 2 Diabetes through Innate Immunity

The escalating epidemic of obesity has driven the prevalence of both type 1 and 2 diabetes mellitus to historically high levels. Chronic low-grade inflammation, which is present in both type 1 and type 2 diabetics, contributes to the pathogenesis of insulin resistance. The accumulation of activated innate immune cells in metabolic tissues results in release of inflammatory mediators, in particular, IL-1 beta and TNF alpha, which promote systemic insulin resistance and beta-cell damage. In this article, we discuss the central role of innate immunity and, in particular, the macrophage in insulin sensitivity and resistance, beta-cell damage, and autoimmune insulitis. We conclude with a discussion of the therapeutic implications of this integrated understanding of diabetic pathology.