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RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study
OBJECTIVE: Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer’s disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cogni...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706319/ https://www.ncbi.nlm.nih.gov/pubmed/26745632 http://dx.doi.org/10.1371/journal.pone.0145521 |
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author | Wang, Pin Huang, Rong Lu, Sen Xia, Wenqing Cai, Rongrong Sun, Haixia Wang, Shaohua |
author_facet | Wang, Pin Huang, Rong Lu, Sen Xia, Wenqing Cai, Rongrong Sun, Haixia Wang, Shaohua |
author_sort | Wang, Pin |
collection | PubMed |
description | OBJECTIVE: Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer’s disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients. METHODS: Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched control individuals were classified as non-MCI. Demographic data were collected, and the soluble RAGE (sRAGE) concentrations, serum AGE-peptide (AGE-P) levels, RAGE Gly82Ser genotype and neuropsychological test results were examined. RESULTS: The MCI group exhibited a decreased sRAGE level (0.87±0.35 vs. 1.05±0.52 ng/ml, p<0.01) and an increased serum AGE-P level (3.54±1.27 vs. 2.71±1.18 U/ml, p<0.01) compared with the control group. Logistic regression analysis indicated that each unit reduction in the sRAGE concentration increased the MCI risk by 54% (OR 0.46[95% CI 0.22–0.96], p = 0.04) and that each unit increase in the AGE-P level increased the MCI risk by 72% in the type 2 diabetes patients (OR 1.72[95% CI 1.31–2.28], p<0.01). The serum sRAGE level was negatively correlated with the score on the trail making test-B (TMT-B) (r = -0.344, p = 0.002), which indicates early cognitive deficits related to diabetes. Moreover, the AGE-P level was positively correlated with multiple cognitive domains (all p<0.05). No significant differences in the neuropsychological test results or serum RAGE concentrations between the different RAGE genotypes or in the RAGE genotype frequencies between the MCI and control groups were identified (all p>0.05). CONCLUSIONS: The RAGE pathway partially mediates AGE-induced MCI in diabetic patients. The serum AGE-P level may serve as a serum biomarker of MCI in these individuals, and sRAGE represents a predictor and even a potential intervention target of early cognitive decline in type 2 diabetes patients. TRIAL REGISTRATION: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060 |
format | Online Article Text |
id | pubmed-4706319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47063192016-01-15 RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study Wang, Pin Huang, Rong Lu, Sen Xia, Wenqing Cai, Rongrong Sun, Haixia Wang, Shaohua PLoS One Research Article OBJECTIVE: Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer’s disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients. METHODS: Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched control individuals were classified as non-MCI. Demographic data were collected, and the soluble RAGE (sRAGE) concentrations, serum AGE-peptide (AGE-P) levels, RAGE Gly82Ser genotype and neuropsychological test results were examined. RESULTS: The MCI group exhibited a decreased sRAGE level (0.87±0.35 vs. 1.05±0.52 ng/ml, p<0.01) and an increased serum AGE-P level (3.54±1.27 vs. 2.71±1.18 U/ml, p<0.01) compared with the control group. Logistic regression analysis indicated that each unit reduction in the sRAGE concentration increased the MCI risk by 54% (OR 0.46[95% CI 0.22–0.96], p = 0.04) and that each unit increase in the AGE-P level increased the MCI risk by 72% in the type 2 diabetes patients (OR 1.72[95% CI 1.31–2.28], p<0.01). The serum sRAGE level was negatively correlated with the score on the trail making test-B (TMT-B) (r = -0.344, p = 0.002), which indicates early cognitive deficits related to diabetes. Moreover, the AGE-P level was positively correlated with multiple cognitive domains (all p<0.05). No significant differences in the neuropsychological test results or serum RAGE concentrations between the different RAGE genotypes or in the RAGE genotype frequencies between the MCI and control groups were identified (all p>0.05). CONCLUSIONS: The RAGE pathway partially mediates AGE-induced MCI in diabetic patients. The serum AGE-P level may serve as a serum biomarker of MCI in these individuals, and sRAGE represents a predictor and even a potential intervention target of early cognitive decline in type 2 diabetes patients. TRIAL REGISTRATION: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060 Public Library of Science 2016-01-08 /pmc/articles/PMC4706319/ /pubmed/26745632 http://dx.doi.org/10.1371/journal.pone.0145521 Text en © 2016 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wang, Pin Huang, Rong Lu, Sen Xia, Wenqing Cai, Rongrong Sun, Haixia Wang, Shaohua RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study |
title | RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study |
title_full | RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study |
title_fullStr | RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study |
title_full_unstemmed | RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study |
title_short | RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study |
title_sort | rage and ages in mild cognitive impairment of diabetic patients: a cross-sectional study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706319/ https://www.ncbi.nlm.nih.gov/pubmed/26745632 http://dx.doi.org/10.1371/journal.pone.0145521 |
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