Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future

Glucose metabolism is normally regulated by a feedback loop including islet beta cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of beta-cell response. If insulin resistance is present, beta cells maintain normal glucose tolerance by increasing insulin output. Only when beta cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although beta-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and beta-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of beta-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.