Reappraising the stereotypes of diabetes in the modern diabetogenic environment

Abstract

The prevailing concentration of blood glucose is a result of the integrated regulation of insulin secretion and insulin action. Nevertheless, the classic stereotypes of diabetes are dichotomous: type 1 diabetes mellitus (T1DM) is attributed to impaired insulin secretion, and type 2 diabetes mellitus (T2DM) is primarily attributed to impaired insulin action (insulin resistance). The available evidence indicates that this view is overly simplistic. Impaired insulin secretion (beta-cell dysfunction) is also a feature of T2DM, and insulin resistance is also a risk factor for the development of T1DM. Moreover, with the increasing incidence of T2DM and T1DM in both developed and developing countries, attributed to environmental factors, the existence of 'hybrid' diabetes types that have clinical and pathogenetic features of both conditions is becoming clearly evident. A common thread across the spectrum of diabetes might be the activation of innate immunological and inflammatory pathways by a proinflammatory environment, which leads to beta-cell dysfunction in T2DM, insulin resistance in both T2DM and T1DM, and enhanced adaptive immunity that kills beta cells in T1DM. Embracing a holistic view of the diabetes syndrome will help us to understand the environmental basis for the epidemic of diabetes and improve preventative strategies.