Methylglyoxal-Induced Glycation of Plasma Albumin: From Biomarker Discovery to Clinical Use for Prediction of New-Onset Diabetes in Individuals with Prediabetes

被引：0

作者：

Oliveira, Arsenio Rodrigues ^{[1
]}

Chevalier, Chloe ^{[1
,2
]}

Wargny, Matthieu ^{[1
,3
]}

Pakulska, Victoria ^{[4
]}

Caradeuc, Cedric ^{[5
,6
]}

Cloteau, Chloe ^{[1
]}

Letertre, Marine P. M. ^{[7
]}

Giraud, Nicolas ^{[5
,6
]}

Bertho, Gildas ^{[5
,6
]}

Bigot-Corbel, Edith ^{[8
]}

Carpentier, Maxime ^{[1
,8
]}

Nouadje, Georges ^{[2
]}

Coute, Yohann ^{[4
]}

Le May, Cedric ^{[1
]}

Cariou, Bertrand ^{[1
]}

Hadjadj, Samy ^{[1
]}

Croyal, Mikael ^{[1
,9
]}

机构：

[1] Nantes Univ, CHU Nantes, Inst Thorax, CNRS,INSERM, 8 Quai Moncousu, F-44000 Nantes, France

[2] Sebia, New Biomarkers Dept, Evry, France

[3] CHU Nantes, INSERM, Pole Hosp Univ Sante Publ 11, CIC 1413,Clin Donnees, Nantes, France

[4] Univ Grenoble Alpes, CEA, INSERM, CNRS,BGE,UA13, FR-2048 Grenoble, France

[5] Univ Paris Cite, CNRS, Lab Chim & Biochim Pharmacol & Toxicol, Paris, France

[6] Univ Paris Cite, Metabo Paris Sante, BioMedTech Facil, Inserm,US36,CNRS,UAR2009, Paris, France

[7] Nantes Univ, CNRS, UMR 6230, CEISAM, Nantes, France

[8] CHU Nantes, G&R Laennec Hosp, Dept Biochem, Bd Jacques Monod, Nantes, France

[9] Nantes Univ, CHU Nantes, Inserm, CNRS,SFR Sante,UMS 016,UMS 3556, Nantes, France

来源：

CLINICAL CHEMISTRY | 2025年

关键词：

END-PRODUCTS; IN-VITRO; RISK; PROTEIN; PEPTIDE; GLUCOSE;

D O I：

10.1093/clinchem/hvaf035

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Background: Methylglyoxal (MGO) is a potent glycating agent that contributes to the pathogenesis of diabetes. However, MGO is unstable in plasma without demanding sample preparation at blood collection, limiting its clinical utility as a biomarker. We aimed to discover reliable MGO-glycated albumin (ALB)-derived biomarkers and to assess their association with new-onset diabetes (NOD) in people with prediabetes. Methods: Bottom-up mass spectrometry-based proteomics was used to discover peptide biomarkers of MGO-glycated ALB, including MGO-derived hydroimidazolone (MGH)-ALB(219-225), which proved to be biologically stable and reliable for large-scale analyses in human plasma. After assay validation, the IT-DIAB (Innovation Th & eacute;rapeutique DIAB & egrave;te) prospective study, conducted in 300 individuals with impaired fasting plasma glucose (FPG) levels (110 to 125 mg/dL, 6.1 to 6.9 mmol/L), was used to assess the association between plasma MGH-ALB(219-225) and NOD, defined as FPG >= 126 mg/dL (7 mmol/L), using Kaplan-Meier curves and Cox models. Results: In total, 113 participants of the IT-DIAB study developed NOD during a median follow-up of 5 years. There was a graded association between the baseline plasma MGH-ALB(219-225) concentration and incident NOD (log-rank P < 0.0001), in contrast to a lack of association for plasma MGO and total or glycated ALB (commercial kit). After adjustment for age, sex, body mass index, FPG, hemoglobin (Hb) A(1c), and ALB, the plasma levels of MGH-ALB(219-225) were associated with NOD (hazard ratio [HR] per one SD [95% CI] = 1.50 [1.26-1.78]; P < 0.0001). Conclusions: MGH-ALB(219-225) is a novel and stable peptide biomarker of MGO-glycated ALB, whose plasma levels are positively associated with an increased risk of NOD in individuals with prediabetes, independently of traditional risk factors. ClinicalTrials.gov Registration Number: NCT01218061

引用

页数：12

共 1 条

[1] Statin use increased new-onset diabetes in hypercholesterolemic individuals: Data from the Korean National Health Insurance Service-National Health Screening Cohort database (NHIS-HEALS)
Kim, Ye-Seul
Han, Ye-Eun
Choi, Eun-A
You, Na-Young
Lee, Jae-Woo
You, Hyo-Sun
Kim, Yonghwan
Kim, Joungyoun
Kang, Hee-Taik
PRIMARY CARE DIABETES, 2020, 14 (03) : 246 - 253

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