• Steven E Kahn, Mark E Cooper, and Stefano Del Prato.
• 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.
• Lancet. 2014 Mar 22; 383 (9922): 106810831068-83.

AbstractGlucose 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.Copyright © 2014 Elsevier Ltd. All rights reserved.

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