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...
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MDPI AG
2022-11-01
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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. |
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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 |
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