{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:52:45Z","timestamp":1791312765554,"version":"4.3.1"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Progression 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>MG-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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1108910","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:02:01Z","timestamp":1674108121000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Methylglyoxal products in pre-symptomatic type 1 diabetes"],"prefix":"10.3389","volume":"14","author":[{"given":"Sarah C.","family":"Shuck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Achenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart O.","family":"Roep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Termini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Hernandez-Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette-Gabriele","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.129","article-title":"Measurement of methylglyoxal by stable isotopic dilution analysis LC-MS\/MS with corroborative prediction in physiological samples","volume":"9","author":"Rabbani","year":"2014","journal-title":"Nat Protoc"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.11.3274","article-title":"Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress","volume":"54","author":"Beisswenger","year":"2005","journal-title":"Diabetes"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1810-7","article-title":"Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes","volume":"48","author":"Ahmed","year":"2005","journal-title":"Diabetologia"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1419","article-title":"Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the endocrine society, and the American diabetes association","volume":"38","author":"Insel","year":"2015","journal-title":"Diabetes Care"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2965","article-title":"Early hyperglycemia detected by continuous glucose monitoring in children at risk for type 1 diabetes","volume":"37","author":"Steck","year":"2014","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI162123","article-title":"Elevations in blood glucose before and after the appearance of islet autoantibodies in children","volume":"132","author":"Warncke","year":"2022","journal-title":"J Clin Invest"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.21565","article-title":"Yield of a public health screening of children for islet autoantibodies in Bavaria, Germany","volume":"323","author":"Ziegler","year":"2020","journal-title":"Jama"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.7b00274","article-title":"Product studies and mechanistic analysis of the reaction of methylglyoxal with deoxyguanosine","volume":"31","author":"Shuck","year":"2018","journal-title":"Chem Res Toxicol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.1007\/s00125-022-05798-z","article-title":"Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening","volume":"65","author":"Weiss","year":"2022","journal-title":"Diabetologia"},{"key":"B10","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.2337\/dc22-S002","article-title":"Classification and diagnosis of diabetes: Standards of medical care in diabetes-2022","volume":"45","author":"Draznin","year":"2022","journal-title":"Diabetes Care"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1108910\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:02:03Z","timestamp":1674108123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1108910\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":10,"alternative-id":["10.3389\/fendo.2023.1108910"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1108910","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]},"article-number":"1108910"}}