Methylglyoxal products in pre-symptomatic type 1 diabetes

被引:5
作者
Shuck, Sarah C. [1 ]
Achenbach, Peter [2 ,3 ,4 ]
Roep, Bart O. [5 ]
Termini, John S. [6 ]
Hernandez-Castillo, Carlos [1 ]
Winkler, Christiane [2 ,4 ]
Weiss, Andreas [2 ,4 ]
Ziegler, Anette-Gabriele [2 ,3 ,4 ]
机构
[1] City Hope Natl Med Ctr, Dept Diabet & Canc Metab, Duarte, CA 91010 USA
[2] German Ctr Environm Hlth, Inst Diabet Res, Helmholtz Munich, Munich, Germany
[3] Tech Univ Munich, Sch Med, Klinikum Rechts Isar, Forschergrp Diabet, Munich, Germany
[4] German Res Ctr Environm Hlth, Forschergrp Diabet eV Helmholtz Munich, Munich, Germany
[5] Leiden Univ, Dept Internal Med, Med Ctr, Leiden, Netherlands
[6] City Hope Natl Med Ctr, Dept Mol Med, Duarte, CA USA
关键词
advanced glycation end products; methylglyoxal; biomarker; RNA adduct; type; 1; diabetes; CHILDREN;
D O I
10.3389/fendo.2023.1108910
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IntroductionProgression to type 1 diabetes has emerged as a complex process with metabolic alterations proposed to be a significant driver of disease. Monitoring products of altered metabolism is a promising tool for determining the risk of type 1 diabetes progression and to supplement existing predictive biomarkers. Methylglyoxal (MG) is a reactive product produced from protein, lipid, and sugar metabolism, providing a more comprehensive measure of metabolic changes compared to hyperglycemia alone. MG forms covalent adducts on nucleic and amino acids, termed MG-advanced glycation end products (AGEs) that associate with type 1 diabetes. MethodsWe tested their ability to predict risk of disease and discriminate which individuals with autoimmunity will progress to type 1 diabetes. We measured serum MG-AGEs from 141 individuals without type 1 diabetes and 271 individuals with type 1 diabetes enrolled in the Fr1da cohort. Individuals with type 1 diabetes were at stages 1, 2, and 3. ResultsWe examined the association of MG-AGEs with type 1 diabetes. MG-AGEs did not correlate with HbA1c or differ between stages 1, 2, and 3 type 1 diabetes. Yet, RNA MG-AGEs were significantly associated with the rate of progression to stage 3 type 1 diabetes, with lower serum levels increasing risk of progression. DiscussionMG-AGEs were able to discriminate which individuals with autoantibodies would progress at a faster rate to stage 3 type 1 diabetes providing a potential new clinical biomarker for determining rate of disease progression and pointing to contributing metabolic pathways.
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