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Review

Type 2 Diabetes: The Pathologic Basis of Reversible β-Cell Dysfunction

  1. Michael G. White,
  2. James A.M. Shaw and
  3. Roy Taylor⇑
  1. Regenerative Medicine for Diabetes Group and Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, U.K.
  1. Corresponding author: Roy Taylor, roy.taylor{at}ncl.ac.uk.
Diabetes Care 2016 Nov; 39(11): 2080-2088. https://doi.org/10.2337/dc16-0619
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Abstract

The reversible nature of early type 2 diabetes has been demonstrated in in vivo human studies. Recent in vivo and in vitro studies of β-cell biology have established that the β-cell loses differentiated characteristics, including glucose-mediated insulin secretion, under metabolic stress. Critically, the β-cell dedifferentiation produced by long-term excess nutrient supply is reversible. Weight loss in humans permits restoration of first-phase insulin secretion associated with the return to normal of the elevated intrapancreatic triglyceride content. However, in type 2 diabetes of duration greater than 10 years, the cellular changes appear to pass a point of no return. This review summarizes the evidence that early type 2 diabetes can be regarded as a reversible β-cell response to chronic positive calorie balance.

  • Received March 21, 2016.
  • Accepted August 23, 2016.
  • © 2016 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Diabetes Care: 39 (11)

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November 2016, 39(11)
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Type 2 Diabetes: The Pathologic Basis of Reversible β-Cell Dysfunction
Michael G. White, James A.M. Shaw, Roy Taylor
Diabetes Care Nov 2016, 39 (11) 2080-2088; DOI: 10.2337/dc16-0619

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Type 2 Diabetes: The Pathologic Basis of Reversible β-Cell Dysfunction
Michael G. White, James A.M. Shaw, Roy Taylor
Diabetes Care Nov 2016, 39 (11) 2080-2088; DOI: 10.2337/dc16-0619
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  • Article
    • Abstract
    • Introduction
    • Etiological Drivers of Type 2 Diabetes
    • The Pathologic Basis of Disease Progression
    • Glucolipotoxicity
    • β-Cell Dedifferentiation
    • Hyperglucagonemia in Type 2 Diabetes
    • Lessons on β-Cell Plasticity From Reversing Type 2 Diabetes
    • A Unifying Hypothesis
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  • Large-for-Gestational-Age Neonates in Type 1 Diabetes and Pregnancy: Contribution of Factors Beyond Hyperglycemia
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© 2019 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.