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.

Analysis of advanced glycation end products in the DHS Mind Study

“…Lastly, AGEs were associated with GMV, supporting prior literature (Srikanth et al, 2013) and implicating AGEs as moderators in T2D-related brain atrophy (Moran et al, 2015) (Table 4). Most associations were found only in non-diabetic individuals which is consistent with some prior studies (Hanssen et al, 2013, Teichert et al, 2015, Scholtes et al, 2014, Yu et al, 2010). The most compelling observation that T2D status affected associations with AGEs was with eGFR.…”

“…For example, Llauradó et al and Turk et al showed that AGEs were highly associated with HbA 1c , while another study performed by de Vos et al found that they were not associated (de Vos et al, 2014, Llaurado et al, 2014, Turk et al, 1998). One possible explanation for such a discrepancy between studies investigating measures of glucose metabolism could originate from diet-introduced AGEs, as plasma levels increase after dietary intake (Teichert et al, 2015). Future studies carefully documenting and analyzing dietary habits of cohorts in which AGEs are assessed may be warranted and in fact, at least one is underway (de Courten et al, 2015).…”

Adipose Tissue Protein Glycoxidation is Associated with Weight‐Loss Potential

“…The latter suggest that changes of adipose tissue CEL could depend on several factors besides glycemic control. Of note, other researchers have found no increased circulating AGE values in patients with insulin resistance, at least at the impaired fasting glucose stage . Consequently, it is possible to speculate that decreased CEL tissue levels in the human cohort could be due to decreased levels of insulin‐driven glycolysis and/or increased protein turnover, both factors that are due to insulin resistance.…”

Effect of imidazoline‐1 receptor agonists on renal dysfunction in rats associated with chronic, sequential fructose and ethanol administration

“…These data are in accordance with the findings of Kansal and Kamble, who showed an increased risk of cardiovascular disease in insulin‐resistant patients due to an impaired lipid profile. Additionally, a study by Teichert et al showed that sAGE levels increased in the early stages of impaired glucose homeostasis. In the same context, chronic ethanol consumption induces metabolic changes, such as hyperlipidaemia and hyperglycaemia, and increases circulating AGEs …”