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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 ? cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of ?-cell response. If insulin resistance is present, ? cells maintain normal glucose tolerance by increasing insulin output. Only when ? cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although ?-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 ?-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 ?-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.

SUBMITTER: Kahn SE 

PROVIDER: S-EPMC4226760 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Kahn Steven E SE   Cooper Mark E ME   Del Prato Stefano S  

Lancet (London, England) 20131203 9922


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  ...[more]

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