title: Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.
abstract: Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-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 β-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 β-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.
authors: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, WA, USA. Electronic address: skahn@uw.edu.
authors: Steven E
authors: SE
authors: Kahn
authors: Diabetes Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors: Mark E
authors: ME
authors: Cooper
authors: Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy.
authors: Stefano
authors: S
authors: Del Prato
mesh_terms: D050110:Bariatric Surgery; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D050416:Glucagon-Secreting Cells / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000150:complications / Q000601:surgery
chemical_list: D007328:Insulin; D005947:Glucose