title: Association between Advanced Glycation End Products and Impaired Fasting Glucose: Results from the SALIA Study.
abstract: Advanced glycation end products (AGEs) may contribute to the development of type 2 diabetes and related complications, whereas their role in the early deterioration of glycaemia is unknown. While previous studies used antibody-based methods to quantify AGEs, data from tandem mass spectrometry coupled liquid chromatography (LC-MS/MS)-based measurements are limited to patients with known diabetes. Here, we used the LC-MS/MS method to test the hypothesis that plasma AGE levels are higher in individuals with impaired fasting glucose (IFG) than in those with normal fasting glucose (NFG). Secondary aims were to assess correlations of plasma AGEs with quantitative markers of glucose metabolism and biomarkers of subclinical inflammation. This study included on 60 women with NFG or IFG (n = 30 each, mean age 74 years) from the German SALIA cohort. Plasma levels of free metabolites (3-deoxyfructose, 3-deoxypentosone, 3-deoxypentulose), two hydroimidazolones, oxidised adducts (carboxymethyllysine, carboxyethyllysine, methionine sulfoxide) and Nε-fructosyllysine were measured using LC-MS/MS. Plasma concentrations of all tested AGEs did not differ between the NFG and IFG groups (all p>0.05). Associations between plasma levels of AGEs and fasting glucose, insulin and HOMA-IR as a measure of insulin resistance were weak (r between -0.2 and 0.2, all p>0.05). The association between 3-deoxyglucosone-derived hydroimidazolone with several proinflammatory biomarkers disappeared upon adjustment for multiple testing. In conclusion, plasma AGEs assessed by LC-MS/MS were neither increased in IFG nor associated with parameters of glucose metabolism and subclinical inflammation in our study. Thus, these data argue against strong effects of AGEs in the early stages of deterioration of glucose metabolism.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Teichert
authors.affiliation: Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Hellwig
authors.affiliation: Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peßler
authors.affiliation: Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hellwig
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Vossoughi
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Sugiri
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vierkötter
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulte
authors.affiliation: Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Freund
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany; Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Tamara
authors.initials: T
authors.lastname: Schikowski
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Krämer
authors.affiliation: Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henle
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D003430:Cross-Sectional Studies; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000097:blood; D005215:Fasting / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D010865:Pilot Projects; D011236:Prediabetic State / Q000097:blood / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D005947:Glucose