{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:29:35Z","timestamp":1791318575659,"version":"4.3.1"},"reference-count":134,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T00:00:00Z","timestamp":1465257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose\/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset\/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer\u2019s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset\/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars\/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or N\u03b5-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention\/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE\/sugar intake restrictions reduce the generation\/accumulation of TAGE, thereby preventing the onset\/progression of LSRD.<\/jats:p>","DOI":"10.3390\/diagnostics6020023","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T02:51:31Z","timestamp":1465267891000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset\/Progression of Lifestyle-Related Diseases"],"prefix":"10.3390","volume":"6","author":[{"given":"Masayoshi","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada-machi, Kahoku, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,7]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation IDF Diabetes Atlas. Available online: http:\/\/www.diabetesatlas.org."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1054-3589(08)60961-8","article-title":"Advanced glycosylation: Chemistry, biology, and implications for diabetes and aging","volume":"23","author":"Bucala","year":"1992","journal-title":"Adv. Pharmacol."},{"key":"ref_3","first-page":"138","article-title":"Pathogenic effects of advanced glycosylation: Biochemical, biologic, and clinical implications for diabetes and aging","volume":"70","author":"Vlassara","year":"1994","journal-title":"Lab. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev.med.46.1.223","article-title":"Advanced protein glycosylation in diabetes and aging","volume":"46","author":"Brownlee","year":"1995","journal-title":"Ann. Rev. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1566524013363735","article-title":"Alternative routes for the formation of immunochemically distinct advanced glycation end-products in vivo","volume":"1","author":"Takeuchi","year":"2001","journal-title":"Curr. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.2174\/1381612054367300","article-title":"Diabetic vascular complications: Pathophysiology, biochemical basis and potential therapeutic strategy","volume":"11","author":"Yamagishi","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2174\/156652406776894536","article-title":"TAGE (toxic AGEs) theory in diabetic complications","volume":"6","author":"Sato","year":"2006","journal-title":"Curr. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"170393","DOI":"10.1155\/2010\/170393","article-title":"Involvement of TAGE-RAGE system in the pathogenesis of diabetic retinopathy","volume":"2010","author":"Takeuchi","year":"2010","journal-title":"J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.2174\/1389450111009011468","article-title":"Involvement of the toxic AGEs (TAGE)-RAGE system in the pathogenesis of diabetic vascular complications: A novel therapeutic strategy","volume":"11","author":"Takeuchi","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/BF03402128","article-title":"Detection of noncarboxymethyllysine and carboxymethyllysine advanced glycation end products (AGE) in serum of diabetic patients","volume":"5","author":"Takeuchi","year":"1999","journal-title":"Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/BF03401779","article-title":"Immunological evidence that non-carboxymethyllysine advanced glycation end-products are produced from short chain sugars and dicarbonyl compounds in vivo","volume":"6","author":"Takeuchi","year":"2000","journal-title":"Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/BF03401969","article-title":"Immunological detection of a novel advanced glycation end-product","volume":"7","author":"Takeuchi","year":"2001","journal-title":"Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/labinvest.2010.62","article-title":"Immunological detection of fructose-derived advanced glycation end-products","volume":"90","author":"Takeuchi","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"845","DOI":"10.3233\/JAD-2009-0974","article-title":"Involvement of toxic AGEs (TAGE) in the pathogenesis of diabetic vascular complications and Alzheimer\u2019s disease","volume":"16","author":"Takeuchi","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1126\/science.12192669","article-title":"Reaction of monosaccharides with proteins: Possible evolutionary significance","volume":"213","author":"Bunn","year":"1981","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1172\/JCI117296","article-title":"Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes","volume":"94","author":"Giardino","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1172\/JCI118563","article-title":"BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells","volume":"97","author":"Giardino","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.fct.2013.06.052","article-title":"Advanced glycation endproducts in food and their effects on health","volume":"60","author":"Poulsen","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.mehy.2004.03.005","article-title":"Alternative routes for the formation of glyceraldehyde-derived AGEs (TAGE) in vivo","volume":"63","author":"Takeuchi","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0074-7742(02)50082-9","article-title":"Polyol pathway and diabetic peripheral neuropathy","volume":"50","author":"Oates","year":"2002","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1254\/jjp.88.123","article-title":"Gene expression of enzymes comprising the polyol pathway in various rat tissues determined by the competitive RT-PCR method","volume":"88","author":"Maekawa","year":"2002","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/dmrr.488","article-title":"Fructose-mediated non-enzymatic glycation: Sweet coupling or bad modification","volume":"20","author":"Schalkwijk","year":"2004","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_23","first-page":"294","article-title":"Adverse effects of dietary fructose","volume":"10","author":"Gaby","year":"2005","journal-title":"Altern. Med. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1096\/fasebj.4.9.2189777","article-title":"Metabolic effects of dietary fructose","volume":"4","author":"Hallfrisch","year":"1990","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"754S","DOI":"10.1093\/ajcn\/58.5.754S","article-title":"Intermediary metabolism of fructose","volume":"58","author":"Mayes","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1093\/jnen\/59.12.1094","article-title":"Neurotoxicity of advanced glycation end-products for cultured cortical neurons","volume":"59","author":"Takeuchi","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20213","DOI":"10.1074\/jbc.M602110200","article-title":"Pigment epithelium-derived factor (PEDF) inhibits advanced glycation end product-induced retinal vascular hyperpermeability by blocking reactive oxygen species-mediated vascular endothelial growth factor expression","volume":"281","author":"Yamagishi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1042\/bj20021371","article-title":"Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury","volume":"370","author":"Yonekura","year":"2003","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1016\/j.diabres.2007.01.030","article-title":"Short-chain aldehyde-derived ligands for RAGE and their actions on endothelial cells","volume":"77","author":"Yamamoto","year":"2007","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.2337\/dc12-0087","article-title":"Positive association between serum level of glyceraldehyde-derived advanced glycation end products (AGEs) and vascular inflammation evaluated by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)","volume":"35","author":"Tahara","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/humrep\/deq388","article-title":"Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology","volume":"26","author":"Jinno","year":"2011","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.mehy.2004.02.042","article-title":"TAGE (toxic AGEs) hypothesis in various chronic diseases","volume":"63","author":"Takeuchi","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s00535-007-2152-7","article-title":"Advanced glycation end products enhance the proliferation and activation of hepatic stellate cells","volume":"43","author":"Iwamoto","year":"2008","journal-title":"J. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"880","DOI":"10.4254\/wjh.v6.i12.880","article-title":"Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies","volume":"6","author":"Takeuchi","year":"2014","journal-title":"World J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1046\/j.0022-202X.2004.22218.x","article-title":"Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions","volume":"122","author":"Abe","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"739852","DOI":"10.1155\/2010\/739852","article-title":"Cancer malignancy is enhanced by glyceraldehyde-derived advanced glycation end-products","volume":"2010","author":"Takino","year":"2010","journal-title":"J. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.3748\/wjg.v16.i42.5334","article-title":"MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells","volume":"16","author":"Sakuraoka","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.3748\/wjg.v18.i15.1781","article-title":"Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC by upregulating VEGF expression","volume":"18","author":"Takino","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_39","first-page":"387","article-title":"Metformin inhibits advanced glycation end products (AGEs)-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing AGEs receptor expression via AMP-activated protein kinase","volume":"45","author":"Ishibashi","year":"2013","journal-title":"Horm. Metab. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.4254\/wjh.v7.i23.2459","article-title":"Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma","volume":"7","author":"Takino","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/1567205043480582","article-title":"Involvement of advanced glycation end-products (AGEs) in Alzheimer\u2019s disease","volume":"1","author":"Takeuchi","year":"2004","journal-title":"Curr. Alzheimer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1177\/1533317506289277","article-title":"Toxic advanced glycation end product (TAGE) theory in Alzheimer\u2019s disease","volume":"21","author":"Sato","year":"2006","journal-title":"Am. J. Alzheimers Dis. Other Demen."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2174\/138161208784139693","article-title":"Possible involvement of advanced glycation end products (AGEs) in the pathogenesis of Alzheimer\u2019s disease","volume":"14","author":"Takeuchi","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1755-5922.2011.00264.x","article-title":"Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects","volume":"30","author":"Ueda","year":"2012","journal-title":"Cardiovasc. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.metabol.2006.02.019","article-title":"Positive association of serum levels of advanced glycation end products with thrombogenic markers in humans","volume":"55","author":"Enomoto","year":"2006","journal-title":"Metabolism"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1055\/s-2007-991176","article-title":"Serum level of advanced glycation end-products (AGEs) is an independent determinant of plasminogen activator inhibitor-1 (PAI-1) in nondiabetic general population","volume":"39","author":"Yamagishi","year":"2007","journal-title":"Horm. Metab. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E12","DOI":"10.1002\/clc.20532","article-title":"Low-density lipoprotein levels are one of the independent determinants of circulating levels of advanced glycation end products in nondiabetic subjects","volume":"32","author":"Yamagishi","year":"2009","journal-title":"Clin. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.phrs.2009.07.003","article-title":"Positive association of circulating level of advanced glycation end products (AGEs) with pigment epithelium-derived factor (PEDF) in a general population","volume":"61","author":"Yamagishi","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.clinbiochem.2012.11.023","article-title":"Serum levels of advanced glycation end products (AGEs) are independently correlated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans","volume":"46","author":"Tahara","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1111\/j.1440-1746.2007.04943.x","article-title":"Elevated levels of serum advanced glycation end-products in patients with nonalcoholic steatohepatitis","volume":"22","author":"Hyogo","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E739","DOI":"10.1210\/jc.2014-3896","article-title":"Clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues by FDG-PET\/CT","volume":"100","author":"Tahara","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2337\/dc14-1435","article-title":"Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function","volume":"38","author":"Kajikawa","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mvr.2007.09.004","article-title":"Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are positively associated with circulating AGEs and soluble form of VCAM-1 in patients with type 2 diabetes","volume":"76","author":"Nakamura","year":"2008","journal-title":"Microvasc. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/dmrr.2537","article-title":"Switching to multiple daily injection therapy with glulisine improves glycemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients","volume":"30","author":"Yanagisawa","year":"2014","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/dmrr.766","article-title":"Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes","volume":"24","author":"Nakamura","year":"2008","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.phrs.2009.05.002","article-title":"Circulating levels of advanced glycation end products (AGE) and interleukin-6 (IL-6) are independent determinants of serum asymmetric dimethylarginine (ADMA) levels in patients with septic shock","volume":"60","author":"Nakamura","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.metabol.2009.05.018","article-title":"Positive association of serum levels of advanced glycation end products and high mobility group box-1 with asymmetric dimethylarginine in nondiabetic chronic kidney disease patients","volume":"58","author":"Nakamura","year":"2009","journal-title":"Metabolism"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.metabol.2006.05.007","article-title":"Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects","volume":"55","author":"Yamagishi","year":"2006","journal-title":"Metabolism"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s10238-007-0146-7","article-title":"Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are correlated with AGEs in both diabetic and non-diabetic subjects","volume":"7","author":"Nakamura","year":"2007","journal-title":"Clin. Exp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10238-006-0115-6","article-title":"Atorvastatin decreases serum levels of advanced glycation end products (AGEs) in patients with type 2 diabetes","volume":"6","author":"Jinnouchi","year":"2006","journal-title":"Clin. Exp. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"304","DOI":"10.4161\/oxim.3.5.13069","article-title":"Atorvastain reduces proteinuria in non-diabetic chronic kidney disease patients partly via lowering serum levels of advanced glycation end products (AGEs)","volume":"3","author":"Nakamura","year":"2010","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ijcme.2014.07.002","article-title":"Effect of statins on the serum soluble form of receptor for advanced glycation end-products and its association with coronary atherosclerosis in patients with angina pectoris","volume":"4","author":"Nozue","year":"2014","journal-title":"IJC Metab. Endocr."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Shimomura, M., Oyama, J., Takeuchi, M., Shibata, Y., Yamamoto, Y., Kawasaki, T., Komoda, H., Kodama, K., Sakuma, M., and Toyoda, S. (2015). Acute effects of statin on reduction of angiopoietin-like 2 and glyceraldehyde-derived advanced glycation end-products levels in patients with acute myocardial infarction: A message from SAMIT (Statin for Acute Myocardial Infarction Trial). Heart Vessels, in press.","DOI":"10.1007\/s00380-015-0773-y"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10238-009-0074-9","article-title":"An \u03b1-glucosidase inhibitor, acarbose treatment decreases serum levels of glyceraldehyde-derived advanced glycation end products (AGEs) in patients with type 2 diabetes","volume":"10","author":"Tsunosue","year":"2010","journal-title":"Clin. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/dmrr.2437","article-title":"Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes","volume":"29","author":"Sakata","year":"2013","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1475-2840-13-15","article-title":"Possible effects of glimepiride beyond glycemic control in patients with type 2 diabetes: A preliminary report","volume":"13","author":"Nakamura","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2353\/ajpath.2008.080442","article-title":"Inflammation at the molecular interface of atherogenesis: An anthropological journey","volume":"173","author":"Lamon","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_68","first-page":"659","article-title":"Cytokine biomarkers, endothelial inflammation, and atherosclerosis in the metabolic syndrome: Emerging concepts","volume":"55","author":"Rizvi","year":"2009","journal-title":"Am. J. Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.2174\/13816128113199990475","article-title":"Role of AGEs-RAGE system in cardiovascular disease","volume":"20","author":"Fukami","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2174\/138920009787522133","article-title":"Clinical utility of acarbose, an alpha-glucosidase inhibitor in cardiometabolic disorders","volume":"10","author":"Yamagishi","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10238-008-0176-9","article-title":"Glyceraldehyde-derived advanced glycation end products (AGEs). A novel biomarker of postprandial hyperglycaemia in diabetic rats","volume":"8","author":"Kitahara","year":"2008","journal-title":"Clin. Exp. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1475-2840-12-5","article-title":"Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: The JAPAN-ACS sub-study","volume":"12","author":"Fukushima","year":"2013","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1016\/j.febslet.2006.04.050","article-title":"Pigment epithelium-derived factor (PEDF) inhibits advanced glycation end product (AGE)-induced C-reactive protein expression in hepatoma cells by suppressing Rac-1 activation","volume":"580","author":"Yoshida","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1007\/s00535-009-0193-9","article-title":"The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicity","volume":"45","author":"Takino","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1024\/0300-9831\/a000150","article-title":"Presence of glyceraldehyde-derived advanced glycation end-products in the liver of insulin-resistant mice","volume":"83","author":"Ebata","year":"2013","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.3748\/wjg.v21.i6.1784","article-title":"In vitro identification of nonalcoholic fatty liver disease-related protein hnRNPM","volume":"21","author":"Takino","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1007\/s00535-010-0203-y","article-title":"Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: Clinical usefulness of AGEs as a biomarker for the attenuation of NASH","volume":"45","author":"Kimura","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4","DOI":"10.23937\/2377-3634\/1410036","article-title":"Toxic AGEs (TAGE) theory in the pathogenesis of NAFLD and ALD","volume":"2","author":"Takeuchi","year":"2015","journal-title":"Int. J. Diabetes Clin. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.mehy.2015.02.002","article-title":"Serum levels of toxic AGEs (TAGE) may be a promising novel biomarker in development and progression of NASH","volume":"84","author":"Takeuchi","year":"2015","journal-title":"Med. Hypotheses"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00401-004-0871-x","article-title":"Glyceraldehyde-derived advanced glycation end products in Alzheimer\u2019s disease","volume":"108","author":"Choei","year":"2004","journal-title":"Acta Neuropathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1136\/bjo.2005.072678","article-title":"Decrease in the glyceraldehyde derived advanced glycation end products in the sera of patients with Vogt-Koyanagi-Harada disease","volume":"89","author":"Kitamura","year":"2005","journal-title":"Br. J. Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1189\/jlb.3A0513-288RRR","article-title":"Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation","volume":"96","author":"Dong","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.mehy.2005.01.015","article-title":"Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients","volume":"64","author":"Yamagishi","year":"2005","journal-title":"Med. Hypotheses"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1158\/1055-9965.EPI-11-0066","article-title":"Advanced glycation end products, soluble receptor for advanced glycation end products, and risk of colorectal cancer","volume":"20","author":"Jiao","year":"2011","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1158\/1055-9965.EPI-11-1139","article-title":"The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: A case-control study within the prospective EPIC Cohort","volume":"21","author":"Grote","year":"2012","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.2337\/db12-1608","article-title":"DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy","volume":"62","author":"Kaida","year":"2013","journal-title":"Diabetes"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/labinvest.2014.5","article-title":"DNA aptamer raised against advanced glycation end products inhibits melanoma growth in nude mice","volume":"94","author":"Ojima","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/jcla.21797","article-title":"Elevation of serum levels of advanced glycation end products in patients with non-B or non-C hepatocellular carcinoma","volume":"29","author":"Kan","year":"2015","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1158\/1055-9965.EPI-15-0422","article-title":"The association between glyceraldehyde-derived advanced glycation end-products and colorectal cancer risk","volume":"24","author":"Kong","year":"2015","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.exger.2006.06.002","article-title":"The molecular basis of the prevention of Alzheimer\u2019s disease through healthy nutrition","volume":"42","author":"Steele","year":"2007","journal-title":"Exp. Geront."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Mittal, K., and Katre, D.P. (2016). Shared links between type 2 diabetes mellitus and Alzheimer\u2019s disease: A review. Diabetes Metab. Syndr.","DOI":"10.1016\/j.dsx.2016.01.021"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2337\/dc15-1588","article-title":"Type 2 diabetes as a risk factor for dementia in women compared with men: A pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia","volume":"39","author":"Chatterjee","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"447","DOI":"10.4196\/kjpp.2014.18.6.447","article-title":"Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer\u2019s disease modifying therapies","volume":"18","author":"Kang","year":"2014","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0197-4580(01)00285-8","article-title":"Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer\u2019s disease and vascular dementia","volume":"23","author":"Tarkowski","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neulet.2004.06.001","article-title":"Increased cerebrospinal fluid levels of transforming growth factor-\u03b21 in Alzheimer\u2019s disease","volume":"367","author":"Zetterberg","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13313","DOI":"10.1038\/srep13313","article-title":"Glyceraldehyde caused Alzheimer\u2019s disease-like alterations in diagnostic marker levels in SH-SY5Y human neuroblastoma cells","volume":"5","author":"Koriyama","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.mehy.2006.12.017","article-title":"Diagnostic utility of serum or cerebrospinal fluid levels of toxic advanced glycation end-products (TAGE) in early detection of Alzheimer\u2019s disease","volume":"69","author":"Takeuchi","year":"2007","journal-title":"Med. Hypotheses"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1111\/jgs.13683","article-title":"Circulating levels of advanced glycation end products in diabetes mellitus-related dementia","volume":"63","author":"Hirose","year":"2015","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neulet.2015.03.002","article-title":"Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia","volume":"593","author":"Takeda","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11739-011-0606-7","article-title":"Cardiovascular risk and dietary sugar intake: Is the link so sweet?","volume":"7","author":"Mucci","year":"2012","journal-title":"Intern. Emerg. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.jacc.2015.08.025","article-title":"Fructose and cardiometabolic health: What the evidence from sugar-sweetened beverages tells us","volume":"66","author":"Malik","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00394-008-0753-4","article-title":"Effects of high-AGE beverage on RAGE and VEGF expressions in the liver and kidneys","volume":"48","author":"Sato","year":"2009","journal-title":"Eur. J. Nutr."},{"key":"ref_103","first-page":"2","article-title":"Assessment of total sugar and glucose concentrations in commonly consumed beverages in Japan","volume":"1","author":"Takeuchi","year":"2015","journal-title":"Nutr. Food Technol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Takeuchi, M., Takino, J., Furuno, S., Shirai, H., Kawakami, M., Muramatsu, M., Kobayashi, Y., and Yamagishi, S. (2015). Assessment of the concentrations of various advanced glycation end-products in beverages and foods that are commonly consumed in Japan. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118652"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nrendo.2011.74","article-title":"AGE restriction in diabetes mellitus: A paradigm shift","volume":"7","author":"Vlassara","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/ejcn.2012.220","article-title":"Dietary advanced glycation end-product restriction for the attenuation of insulin resistance, oxidative stress and endothelial dysfunction: A systematic review","volume":"67","author":"Kellow","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.3945\/jn.113.189480","article-title":"Dietary intake of advanced glycation end products did not affect endothelial function and inflammation in healthy adults in a randomized controlled trial","volume":"44","author":"Semba","year":"2014","journal-title":"J. Nutr."},{"key":"ref_108","first-page":"415","article-title":"Current perspectives on the health risks associated with the consumption of advanced glycation end products: Recommendations for dietary management","volume":"8","author":"Palimeri","year":"2015","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1755-5922.2010.00177.x","article-title":"Serum levels of advanced glycation end products (AGEs) are independent correlates of insulin resistance in non-diabetic subjects","volume":"30","author":"Tahara","year":"2012","journal-title":"Cardiovasc. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"180","DOI":"10.2119\/2005-00034.Ueda","article-title":"Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure","volume":"12","author":"Ueda","year":"2006","journal-title":"Mol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.jada.2004.05.214","article-title":"Advanced glycoxidation end products in commonly consumed foods","volume":"104","author":"Goldberg","year":"2004","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jada.2010.03.018","article-title":"Advanced glycation end products in foods and a practical guide to their reduction in the diet","volume":"110","author":"Uribarri","year":"2010","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/ejcn.2011.139","article-title":"Dietary intake associated with serum versus urinary carboxymethyl-lysine, a major advanced glycation end product, in adults: The Energetics Study","volume":"66","author":"Semba","year":"2012","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/s00726-012-1427-3","article-title":"Digestibility of extruded proteins and metabolic transit of N\u03b5-carboxymethyllysine in rats","volume":"44","author":"Alamir","year":"2013","journal-title":"Amino Acids"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1073\/pnas.94.12.6474","article-title":"Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy","volume":"94","author":"Koschinsky","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3390\/nu8030125","article-title":"Dietary advanced glycation end products and risk factors for chronic disease: A systematic review of randomised controlled trials","volume":"8","author":"Clarke","year":"2016","journal-title":"Nutrients"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1136\/bmj.38077.458438.EE","article-title":"Preventing childhood obesity by reducing consumption of carbonated drinks: Cluster randomised controlled trial","volume":"328","author":"James","year":"2004","journal-title":"BMJ"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1210\/jc.2003-031855","article-title":"Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women","volume":"89","author":"Teff","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_119","unstructured":"Joint World Health Organization (WHO)\/Food and Agriculture Organization (FAO) Expert Consultation (2003). Diet, Nutrition and the Prevention of Chronic Diseases, World Health Organization."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.jada.2010.06.008","article-title":"Fructose: Metabolic, hedonic, and societal parallels with ethanol","volume":"110","author":"Lustig","year":"2010","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.nut.2010.02.014","article-title":"Fructose and metabolic diseases: New findings, new questions","volume":"26","author":"Tappy","year":"2010","journal-title":"Nutrition"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.2105\/AJPH.2012.300974","article-title":"Relationship of soft drink consumption to global overweight, obesity, and diabetes: A cross-national analysis of 75 countries","volume":"103","author":"Basu","year":"2013","journal-title":"Am. J. Public Health"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.physbeh.2010.01.036","article-title":"Sugar-sweetened beverages and risk of obesity and type 2 diabetes: Epidemiologic evidence","volume":"100","author":"Hu","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3945\/ajcn.113.058362","article-title":"Sugar-sweetened beverages and weight gain in children and adults: A systematic review and meta-analysis","volume":"98","author":"Malik","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s11892-012-0259-6","article-title":"Sweeteners and risk of obesity and type 2 diabetes: The role of sugar-sweetened beverages","volume":"12","author":"Malik","year":"2012","journal-title":"Curr. Diab. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1161\/CIRCULATIONAHA.107.689935","article-title":"Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community","volume":"116","author":"Dhingra","year":"2007","journal-title":"Circulation"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"688","DOI":"10.2337\/dc08-1799","article-title":"Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"32","author":"Nettleton","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.3945\/ajcn.2008.27140","article-title":"Sweetened beverage consumption and risk of coronary heart disease in women","volume":"89","author":"Fung","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1161\/CIRCULATIONAHA.109.911164","article-title":"Reducing consumption of sugar-sweetened beverages is associated with reduced blood pressure: A prospective study among United States adults","volume":"121","author":"Chen","year":"2010","journal-title":"Circulation"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1161\/CIRCULATIONAHA.109.192627","article-title":"Dietary sugars intake and cardiovascular health: A scientific statement from the American Heart Association","volume":"120","author":"Jonson","year":"2009","journal-title":"Circulation"},{"key":"ref_131","unstructured":"WHO guideline: Sugars Intake for Adults and Children. Available online: http:\/\/apps.who.int\/iris\/bitstream\/10665\/149782\/1\/9789241549028_eng.pdf?ua=1."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3945\/ajcn.111.018366","article-title":"Consumption of added sugars is decreasing in the United States","volume":"94","author":"Welsh","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3945\/ajcn.112.050997","article-title":"Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l\u2019Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort","volume":"97","author":"Fagherazzi","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"h3576","DOI":"10.1136\/bmj.h3576","article-title":"Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: Systematic review, meta-analysis, and estimation of population attributable fraction","volume":"351","author":"Imamura","year":"2015","journal-title":"BMJ"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/6\/2\/23\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:25:06Z","timestamp":1760210706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/6\/2\/23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,7]]},"references-count":134,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["diagnostics6020023"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics6020023","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,7]]}}}