β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment
- Philippe A. Halban1,
- Kenneth S. Polonsky2,
- Donald W. Bowden3,
- Meredith A. Hawkins4,
- Charlotte Ling5,
- Kieren J. Mather6,
- Alvin C. Powers7,
- Christopher J. Rhodes8,
- Lori Sussel9 and
- Gordon C. Weir10
- 1Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
- 2Department of Medicine, Section of Endocrinology, University of Chicago, Chicago, IL
- 3Center for Genomics and Personalized Medicine Research and Center for Diabetes Research, Wake Forest University, Winston-Salem, NC
- 4Department of Medicine (Endocrinology) and Global Diabetes Institute, Albert Einstein College of Medicine, Bronx, NY
- 5Department of Clinical Sciences, Lund University, Lund, Sweden
- 6Department of Endocrinology, Indiana University, Indianapolis, IN
- 7Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University School of Medicine, Nashville, TN
- 8Kovler Diabetes Center, Department of Medicine, University of Chicago, Chicago, IL
- 9Naomi Berrie Diabetes Center, Columbia University, New York, NY
- 10Joslin Diabetes Center, Harvard Medical School, Boston, MA
- Corresponding author: Philippe A. Halban, , or Kenneth S. Polonsky, .
P.A.H. and K.S.P. contributed equally to this study.
OBJECTIVE This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment.
RESEARCH DESIGN AND METHODS A group of experts participated in a conference on 14–16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations.
RESULTS The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions.
CONCLUSIONS β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1) impact the natural history of β-cell failure; 2) identify and characterize genetic loci for T2D; 3) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) develop alternative sources of β-cells for cell-based therapy; 5) focus on metabolic environment to provide indirect benefit to β-cells; 6) improve understanding of the physiology of responses to bypass surgery; and 7) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.
This article is based on a conference jointly sponsored by the Endocrine Society and the American Diabetes Association and supported by an educational grant from Novo Nordisk, Sanofi, and Lilly USA.
This article has been copublished in the Journal of Clinical Endocrinology & Metabolism.
- Received February 12, 2014.
- Accepted March 28, 2014.
- © 2014 by the American Diabetes Association and the Endocrine Society.
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