Autoimmune Inflammation and Insulin Resistance: Hallmarks So Far and Yet So Close to Explain Diabetes Endotypes

Diabetes mellitus can be categorized into two major variants, type 1 and type 2. A number of traits such as clinical phenotype, age at disease onset, genetic background, and underlying pathogenesis distinguish the two forms.

Recent evidence indicates that type 1 diabetes can be accompanied by insulin resistance and type 2 diabetes exhibits self-reactivity. These two previously unknown conditions can influence the progression and outcome of the disease. Unlike most conventional considerations, diabetes appears to consist of a spectrum of intermediate phenotypes that includes monogenic and polygenic loci linked to inflammatory processes including autoimmunity, beta cell impairment, and insulin resistance. Here we discuss why a shift of the classical bi-modal view of diabetes (autoimmune vs. non-autoimmune) is necessary in favor of a model of an immunological continuum of endotypes lying between the two extreme "insulin-resistant" and "autoimmune beta cell targeting," shaped by environmental and genetic factors which contribute to determine specific immune-conditioned outcomes.