Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis

Abstract

The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.

Figure 1

Genetic and environmental risk factors impact inflammation, autoimmunity, and metabolic stress. These states affect β-cell mass and/or function such that insulin levels are eventually unable to respond sufficiently to insulin demands, leading to hyperglycemia levels sufficient to diagnose diabetes. In some cases, genetic and environmental risk factors and gene–environment interactions can directly impact β-cell mass and/or function. Regardless of the pathophysiology of diabetes, chronic high blood glucose levels are associated with microvascular and macrovascular complications that increase morbidity and mortality for people with diabetes. This model positions β-cell destruction and/or dysfunction as the necessary common factor to all forms of diabetes.