Association between Advanced Glycation End Products and Impaired Fasting Glucose: Results from the SALIA Study

PLoS One. 2015 May 27;10(5):e0128293. doi: 10.1371/journal.pone.0128293. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Chromatography, Liquid / methods
  • Cross-Sectional Studies
  • Deoxyglucose / analogs & derivatives
  • Deoxyglucose / blood
  • Fasting / blood*
  • Female
  • Glucose / metabolism*
  • Glycation End Products, Advanced / blood*
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism
  • Insulin / blood
  • Insulin Resistance / physiology
  • Pilot Projects
  • Prediabetic State / blood
  • Prediabetic State / metabolism
  • Tandem Mass Spectrometry / methods

Substances

  • Biomarkers
  • Blood Glucose
  • Glycation End Products, Advanced
  • Insulin
  • Deoxyglucose
  • 3-deoxyglucosone
  • Glucose

Grants and funding

This study was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG; HE-4510/2-1, KR 1938/3-1, LU 691/4-1). SALIA received funds from the Ministry of the Environment of the State of North Rhine-Westphalia (Düsseldorf, Germany) and the Federal Ministry of the Environment (Berlin, Germany). The follow-up investigation was funded by the DGUV (German statutory accident assurance) VT 266.1. This work was supported by the Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW), the German Federal Ministry of Health (BMG) and in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.