Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy
Open accessAbstract
Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking species (glycotoxins) that contribute to the vascular and renal complications of diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD). The aim of this study was to examine the oral absorption and renal clearance kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and five healthy subjects (NL) received a single meal of egg white (56 g protein), cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA and for AGE-specific crosslinking reactivity, based on complex formation with 125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8, P < 0.05): the area under the curve for serum ( approximately 10% of ingested AGE) correlated directly with severity of KD; renal excretion of dietary AGE, although normally incomplete (only approximately 30% of amount absorbed), in DM it correlated inversely with degree of albuminuria, and directly with creatinine clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE-meal serum exhibited increased AGE-crosslinking activity (two times above baseline serum AGE, three times above negative control), which was inhibited by aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is markedly suppressed in diabetic nephropathy patients, (ii) daily influx of dietary AGEs includes glycotoxins that may constitute an added chronic risk for renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may greatly reduce the burden of AGEs in diabetic patients and possibly improve prognosis.
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In vitro, vitamin E exerts a range of anti-inflammatory actions on pro-inflammatory cytokine and eicosanoid production and on adhesive interactions of monocytes with endothelial cells.
“In vitro, vitamin E exerts a range of anti-inflammatory actions with regard to the production of pro-inflammatory cytokines and eicosanoids and adhesive interactions of monocytes with endothelial cells (750,759 -761) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [761]
Around 10-30% of CML, CEL, pentosidine, and pyrraline are absorbed depending on their chemical characteristics.
“Nonetheless, the rate and the mechanisms of absorption of CLM, CEL, pentosidine, and pyrraline have been reported with around 10-30% being absorbed depending on their chemical characteristics.[28][29][30]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [28]
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- Authors
- Koschinsky, T., He, C.-J., Mitsuhashi, T., Bucala, R., Liu, C., Buenting, C., Heitmann, K., & Vlassara, H.
- Affiliations
- Laboratory of Diabetes and Aging, The Picower Institute for Medical Research, Manhasset, NY 11030; and Diabetes Research Institute, auf Hennekamp 65, Dusseldorf, Germany
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-06-10
- Volume
- 94
- Issue
- 12
- Pages
- 6474-6479
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21074
- OpenAlex
- W1971209988
- Cited by
- 792
- References
- 25
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 28 · 2023: 25 · 2022: 36 · 2021: 36 · 2020: 30 · 2019: 48 · 2018: 30 · 2017: 44 · 2016: 38 · 2015: 38 · 2014: 35 · 2013: 33 · 2012: 33
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01ag006943-11)
- National Institute on Aging (AG06943-10)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
- Keywords
- advanced glycation end products, diabetic nephropathy, oral absorption, renal clearance, dietary AGEs, fructose, egg white, albuminuria, creatinine clearance, renal failure, aminoguanidine, fibronectin, diabetes mellitus, kidney disease
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Albuminuria, Creatinine, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diet, Diabetic, Diabetic Nephropathies, Female, Food Analysis, Fructose, Humans, Intestinal Absorption, Male, Middle Aged, Ovalbumin, Reference Values, Risk Factors, Glycation End Products, Advanced
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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