Abstract
Despite new and effective drug therapies, insulin resistance (IR), type 2 diabetes mellitus (T2D) and its complications remain major medical challenges. It is accepted that IR, often associated with over-nutrition and obesity, results from chronically elevated oxidant stress (OS) and chronic inflammation. Less acknowledged is that a major cause for this inflammation is excessive consumption of advanced glycation end products (AGEs) with the standard western diet. AGEs, which were largely thought as oxidative derivatives resulting from diabetic hyperglycemia, are increasingly seen as a potential risk for islet β-cell injury, peripheral IR and diabetes. Here we discuss the relationships between exogenous AGEs, chronic inflammation, IR, and T2D. We propose that under chronic exogenous oxidant AGE pressure the depletion of innate defense mechanisms is an important factor, which raises susceptibility to inflammation, IR, T2D and its complications. Finally we review evidence on dietary AGE restriction as a nonpharmacologic intervention, which effectively lowers AGEs, restores innate defenses and improves IR, thus, offering new perspectives on diabetes etiology and therapy.
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Acknowledgments
This work was supported by grants AG-23188 and AG-09453 (to H.V.) and from the National Institutes of Health, National Institute of Research Resources (Grant M01-RR-00071) to the General Clinical Research Center at Mount Sinai School of Medicine.
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Conflict of Interest
Helen Vlassara has received grant support and support for travel to meetings for the study or otherwise from Sanofi for a co-investigator-initiated clinical investigation. She has patents (planned, pending or issued) from Cell Biolabs for development of monoclonal antibody, and receives royalties for monoclonal antibody. Her husband is principal investigator in an investigator-initiated clinical trial, supported by Sanofi.
Jaime Uribarri is a co-author on a book on AGE-less Diet.
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This review does not contain original description of any studies with human or animal subjects performed by any of the authors.
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This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance
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Vlassara, H., Uribarri, J. Advanced Glycation End Products (AGE) and Diabetes: Cause, Effect, or Both?. Curr Diab Rep 14, 453 (2014). https://doi.org/10.1007/s11892-013-0453-1
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DOI: https://doi.org/10.1007/s11892-013-0453-1