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

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, glyox...

Full description

Bibliographic Details
Main Authors: Melinda Csongová, Jean L. J. M. Scheijen, Marjo P. H. van de Waarenburg, Radana Gurecká, Ivana Koborová, Tamás Tábi, Éva Szökö, Casper G. Schalkwijk, Katarína Šebeková
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/22/4929
_version_ 1797464263617413120
author Melinda Csongová
Jean L. J. M. Scheijen
Marjo P. H. van de Waarenburg
Radana Gurecká
Ivana Koborová
Tamás Tábi
Éva Szökö
Casper G. Schalkwijk
Katarína Šebeková
author_facet Melinda Csongová
Jean L. J. M. Scheijen
Marjo P. H. van de Waarenburg
Radana Gurecká
Ivana Koborová
Tamás Tábi
Éva Szökö
Casper G. Schalkwijk
Katarína Šebeková
author_sort Melinda Csongová
collection DOAJ
description 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.
first_indexed 2024-03-09T18:04:59Z
format Article
id doaj.art-0488a6bdf12e4b3ab12242af2451cda6
institution Directory Open Access Journal
issn 2072-6643
language English
last_indexed 2024-03-09T18:04:59Z
publishDate 2022-11-01
publisher MDPI AG
record_format Article
series Nutrients
spelling doaj.art-0488a6bdf12e4b3ab12242af2451cda62023-11-24T09:33:27ZengMDPI AGNutrients2072-66432022-11-011422492910.3390/nu14224929Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control StudyMelinda Csongová0Jean L. J. M. Scheijen1Marjo P. H. van de Waarenburg2Radana Gurecká3Ivana Koborová4Tamás Tábi5Éva Szökö6Casper G. Schalkwijk7Katarína Šebeková8Institute of Molecular Biomedicine, Medical Faculty, Comenius University, 811 07 Bratislava, SlovakiaDepartment of Internal Medicine, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsDepartment of Internal Medicine, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsInstitute of Molecular Biomedicine, Medical Faculty, Comenius University, 811 07 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Medical Faculty, Comenius University, 811 07 Bratislava, SlovakiaDepartment of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, 1089 Budapest, HungaryDepartment of Internal Medicine, Maastricht University Medical Centre, 6200 MD Maastricht, The NetherlandsInstitute of Molecular Biomedicine, Medical Faculty, Comenius University, 811 07 Bratislava, Slovakiaα-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.https://www.mdpi.com/2072-6643/14/22/4929advanced glycation end productsα-dicarbonylsD-lactatecardiometabolic riskinsulin resistancesex differences
spellingShingle Melinda Csongová
Jean L. J. M. Scheijen
Marjo P. H. van de Waarenburg
Radana Gurecká
Ivana Koborová
Tamás Tábi
Éva Szökö
Casper G. Schalkwijk
Katarína Šebeková
Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study
Nutrients
advanced glycation end products
α-dicarbonyls
D-lactate
cardiometabolic risk
insulin resistance
sex differences
title Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study
title_full Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study
title_fullStr Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study
title_full_unstemmed Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study
title_short Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study
title_sort association of α dicarbonyls and advanced glycation end products with insulin resistance in non diabetic young subjects a case control study
topic advanced glycation end products
α-dicarbonyls
D-lactate
cardiometabolic risk
insulin resistance
sex differences
url https://www.mdpi.com/2072-6643/14/22/4929
work_keys_str_mv AT melindacsongova associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT jeanljmscheijen associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT marjophvandewaarenburg associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT radanagurecka associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT ivanakoborova associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT tamastabi associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT evaszoko associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT caspergschalkwijk associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy
AT katarinasebekova associationofadicarbonylsandadvancedglycationendproductswithinsulinresistanceinnondiabeticyoungsubjectsacasecontrolstudy