Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study

• Published in: Nutrients Vol. 14; no. 22; p. 4929
• Main Authors: Csongová, Melinda, Scheijen, Jean L. J. M., van de Waarenburg, Marjo P. H., Gurecká, Radana, Koborová, Ivana, Tábi, Tamás, Szökö, Éva, Schalkwijk, Casper G., Šebeková, Katarína
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.11.2022; MDPI
• Subjects: Age; Body fat; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Chronic illnesses; Creatinine; Diabetes; Diabetes therapy; Female; Glycation End Products, Advanced; High density lipoprotein; Humans; Insulin; Insulin Resistance; Kinases; Laboratories; Male; Pathogenesis; Protein binding; Proteins; Sample size; Software; Type 2 diabetes; Variance analysis; United States > US; Austria; Japan; D-lactate; sVAP-1; cardiometabolic risk; α-dicarbonyls; sRAGE; advanced glycation end products; insulin resistance; sex differences
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14224929

α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal, glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, and urinary AGEs using the UPLC/MS-MS method; soluble receptors for AGEs (sRAGE), and cardiometabolic risk markers in 142 (49% females) insulin resistant (Quantitative Insulin Sensitivity Check Index (QUICKI) ≤ 0.319) and 167 (47% females) age-, and waist-to-height ratio-matched insulin-sensitive controls aged 16-to-22 years. The between-group comparison was performed using the two-factor (sex, presence/absence of insulin resistance) analysis of variance; multiple regression via the orthogonal projection to latent structures model. In comparison with their insulin-sensitive peers, young healthy insulin-resistant individuals without diabetes manifest alterations throughout the α-dicarbonyls-AGEs-sRAGE axis, dominated by higher 3-deoxyglucosone levels. Variables of α-dicarbonyls-AGEs-sRAGE axis were associated with insulin sensitivity independently from cardiometabolic risk markers, and sex-specifically. Cleaved RAGE associates with QUICKI only in males; while multiple α-dicarbonyls and AGEs independently associate with QUICKI particularly in females, who displayed a more advantageous cardiometabolic profile compared with males. Further studies are needed to elucidate whether interventions alleviating dicarbonyl stress ameliorate insulin resistance.