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Objectives: To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance.Study Design: Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography-tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance.Results: Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up.Conclusion: Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control. [ABSTRACT FROM AUTHOR]

Résumé La carbamylation correspond à la fixation non enzymatique d’acide isocyanique, principalement dérivé de la décomposition de l’urée, sur les groupements aminés des protéines, et participe à leur vieillissement moléculaire. Ce processus est amplifié au cours de l’insuffisance rénale chronique (IRC), en raison de l’hyperurémie, et dans d’autres pathologies comme l’athérosclérose, où l’acide isocyanique peut être formé à partir du thiocyanate par la myéloperoxydase dans les plaques d’athérome. La carbamylation provoque des modifications structurales et fonctionnelles des protéines, altérant leurs rôles biologiques et leurs interactions avec les cellules. De nombreuses preuves expérimentales in vitro ont montré l’effet délétère potentiel des protéines carbamylées sur les fonctions cellulaires et tissulaires. Les produits de carbamylation ( carbamylation-derived products , CDP), et principalement l’homocitrulline, s’accumulent dans l’organisme, essentiellement sur les protéines à durée de vie longue, et peuvent participer à l’apparition de différentes complications de l’IRC, en particulier les atteintes cardiovasculaires, la fibrose rénale, ou encore les troubles nutritionnels et métaboliques. Des études cliniques récentes ont confirmé le lien entre carbamylation des protéines sériques et morbi-mortalité chez des patients atteints d’insuffisance rénale chronique ou en hémodialyse. Certains produits de carbamylation pourraient être utilisés comme biomarqueurs dans ces pathologies. Carbamylation corresponds to the non-enzymatic binding of isocyanic acid, mainly derived from urea decomposition, on amino groups of proteins, and participates in their molecular aging. This process is increased during chronic kidney disease (CKD) because of hyperuremia, and in other pathologies like atherosclerosis, where isocyanic may be formed from thiocyanate by myeloperoxidase in atheroma plates. Carbamylation triggers structural and functional modifications of proteins, thus impairing their biological roles and their interactions with cells. Much experimental evidence in vitro has shown the potential deleterious effects of carbamylated proteins on cell and tissue functions. Carbamylation-derived products (CDPs), and especially their major component homocitrulline, accumulate in organism in long half-life proteins, and may participate in the development of different complications of CKD, especially cardiovascular diseases, renal fibrosis, or nutritional and metabolic troubles. Recent clinical studies have confirmed the link between serum protein carbamylation and morbi-mortality in patients suffering from CKD or undergoing hemodialysis. Some CDPs could be used as biomarkers in these pathologies. [ABSTRACT FROM AUTHOR]

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Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Conflicting results have been published concerning serum β microglobulin (β-M) kinetics during dialysis with a cuprophane membrane which is not permeable for the protein. We have investigated the hypothesis that the apparent increase of free serum β-M could result from extracellular fluid volume (ECV) contraction. Using inulin, ECV was measured before and 1 h after a dialysis session with a sodium dialysate concentration of 145 mmol/l. Dialysis was performed either with a cuprophane or a high-flux membrane. Transcellular water shift and changes in β-M concentration were calculated from total body water changes (ultrafiltration) and ECV. ECV decreased from a predialysis value of 16.6±3.51 (mean±SD) (24.9% bodyweight) to a postdialysis value of 11.9±2.11 (19.8% bodyweight). Ultrafiltration was only 3.1±1.01, indicating concomitant water shift from ECV to intracellular fluid space. A significant decrease in corrected β-M concentration was found for high-flux membranes. However, postdialysis β-M did not change significantly after dialysis with cellulosic membranes. In conclusion, the apparent increase of serum β-M concentration measured during dialysis with cellulosic membranes may be explained by ECV contraction. These results have to be taken into account for any pathogenic mechanism of the β-M-associated amyloidosis occurring in long-term haemodialysed patients. [ABSTRACT FROM PUBLISHER]