{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:45:03Z","timestamp":1791942303010,"version":"4.3.4"},"reference-count":18,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["X01DK118575"],"award-info":[{"award-number":["X01DK118575"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Diabetic Complications Consortium"},{"name":"NIDDK Central Repository"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["1R21DK127285"],"award-info":[{"award-number":["1R21DK127285"]}]},{"name":"NIH","award":["R01CA176611"],"award-info":[{"award-number":["R01CA176611"]}]},{"name":"NIH","award":["R01DK065073"],"award-info":[{"award-number":["R01DK065073"]}]},{"name":"NIH","award":["R01DK081705"],"award-info":[{"award-number":["R01DK081705"]}]},{"name":"Wanek Family Project for the Cure of Type Diabetes at City of"},{"name":"National Cancer Institute of the National Institutes of Health","award":["P30CA033572"],"award-info":[{"award-number":["P30CA033572"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>More than 30% of patients with type 1 diabetes develop diabetic kidney disease (DKD), which significantly increases mortality risk. The Diabetes Control and Complications Trial (DCCT) and follow-up study, Epidemiology of Diabetes Interventions and Complications (EDIC), established that glycemic control measured by HbA1c predicts DKD risk. However, the continued high incidence of DKD reinforces the urgent need for additional biomarkers to supplement HbA1c. Here, we assessed biomarkers induced by methylglyoxal (MG), a metabolic by-product that forms covalent adducts on DNA, RNA, and proteins, called MG adducts. Urinary MG adducts were measured in samples from patients with type 1 diabetes enrolled in DCCT\/EDIC who did (case patients; n = 90) or did not (control patients; n = 117) develop DKD. Univariate and multivariable analyses revealed that measurements of MG adducts independently predict DKD before established DKD biomarkers such as glomerular filtration rate and albumin excretion rate. Elevated levels of MG adducts bestowed the greatest risk of developing DKD in a multivariable model that included HbA1c and other clinical covariates. Our work establishes a novel class of biomarkers to predict DKD risk and suggests that inclusion of MG adducts may be a valuable tool to improve existing predictors of complications like DKD prior to overt disease, and to aid in identifying at-risk individuals and personalized risk management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0277","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T16:04:40Z","timestamp":1700064280000},"page":"611-617","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":23,"title":["Methylglyoxal Adducts Are Prognostic Biomarkers for Diabetic Kidney Disease in Patients With Type 1 Diabetes"],"prefix":"10.2337","volume":"73","author":[{"given":"Seigmund Wai Tsuen","family":"Lai","sequence":"first","affiliation":[{"name":"1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Hernandez-Castillo","sequence":"additional","affiliation":[{"name":"1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin De Jesus Lopez","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tala","family":"Zoukari","sequence":"additional","affiliation":[{"name":"1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Talley","sequence":"additional","affiliation":[{"name":"2Biostatistics and Mathematical Oncology Core, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Paquin","sequence":"additional","affiliation":[{"name":"1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"3Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart O.","family":"Roep","sequence":"additional","affiliation":[{"name":"4Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Kaddis","sequence":"additional","affiliation":[{"name":"5Department of Diabetes and Cancer Discovery Science, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Natarajan","sequence":"additional","affiliation":[{"name":"3Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Termini","sequence":"additional","affiliation":[{"name":"6Department of Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6291-1553","authenticated-orcid":false,"given":"Sarah C.","family":"Shuck","sequence":"additional","affiliation":[{"name":"1Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"2024032018502521200_B1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1681\/ASN.2012070718","article-title":"Kidney disease and increased mortality risk in type 2 diabetes","volume":"24","author":"Afkarian","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"2024032018502521200_B2","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.2337\/db08-1543","article-title":"The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes","volume":"58","author":"Groop","year":"2009","journal-title":"Diabetes"},{"key":"2024032018502521200_B3","doi-asserted-by":"crossref","first-page":"e1001321","DOI":"10.1371\/journal.pmed.1001321","article-title":"Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study","volume":"9","author":"Livingstone","year":"2012","journal-title":"PLoS Med"},{"key":"2024032018502521200_B4","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1007\/s00125-010-1860-3","article-title":"In the absence of renal disease, 20\u00a0year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study","volume":"53","author":"Orchard","year":"2010","journal-title":"Diabetologia"},{"key":"2024032018502521200_B5","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.2337\/dc06-1161","article-title":"Type 1 diabetes and coronary artery disease","volume":"29","author":"Orchard","year":"2006","journal-title":"Diabetes Care"},{"key":"2024032018502521200_B6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: an update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int Suppl (2011)"},{"key":"2024032018502521200_B7","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.2337\/diacare.23.8.1197","article-title":"Hemoglobinopathies and HbA(1c) measurement","volume":"23","author":"Gunton","year":"2000","journal-title":"Diabetes Care"},{"key":"2024032018502521200_B8","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1021\/acs.chemrestox.2c00160","article-title":"Methylglyoxal and its adducts: induction, repair, and association with disease","volume":"35","author":"Lai","year":"2022","journal-title":"Chem Res Toxicol"},{"key":"2024032018502521200_B9","doi-asserted-by":"crossref","first-page":"1969","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":"2024032018502521200_B10","doi-asserted-by":"crossref","first-page":"105","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":"2024032018502521200_B11","doi-asserted-by":"crossref","first-page":"1108910","DOI":"10.3389\/fendo.2023.1108910","article-title":"Methylglyoxal products in pre-symptomatic type 1 diabetes","volume":"14","author":"Shuck","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2024032018502521200_B12","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/bj3240565","article-title":"N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins","volume":"324","author":"Ahmed","year":"1997","journal-title":"Biochem J"},{"key":"2024032018502521200_B13","doi-asserted-by":"crossref","first-page":"915486","DOI":"10.1155\/2015\/915486","article-title":"Increased DNA dicarbonyl glycation and oxidation markers in patients with type 2 diabetes and link to diabetic nephropathy","volume":"2015","author":"Waris","year":"2015","journal-title":"J Diabetes Res"},{"key":"2024032018502521200_B14","doi-asserted-by":"crossref","first-page":"824","DOI":"10.2337\/diab.44.7.824","article-title":"Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes","volume":"44","author":"Beisswenger","year":"1995","journal-title":"Diabetes"},{"key":"2024032018502521200_B15","doi-asserted-by":"crossref","first-page":"968","DOI":"10.2337\/dc10-1675","article-title":"Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the Joslin 50-Year Medalist Study","volume":"34","author":"Sun","year":"2011","journal-title":"Diabetes Care"},{"key":"2024032018502521200_B16","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.2337\/dc12-2689","article-title":"Early progression of diabetic nephropathy correlates with methylglyoxal-derived advanced glycation end products","volume":"36","author":"Beisswenger","year":"2013","journal-title":"Diabetes Care"},{"key":"2024032018502521200_B17","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/sj.ki.5002033","article-title":"Tandem mass spectrometry measurements of creatinine in mouse plasma and urine for determining glomerular filtration rate","volume":"71","author":"Takahashi","year":"2007","journal-title":"Kidney Int"},{"key":"2024032018502521200_B18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/jnc.15656","article-title":"DJ-1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons","volume":"162","author":"Mazza","year":"2022","journal-title":"J Neurochem"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/73\/4\/611\/749410\/db230277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/73\/4\/611\/749410\/db230277.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T14:50:51Z","timestamp":1710946251000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/73\/4\/611\/153869\/Methylglyoxal-Adducts-Are-Prognostic-Biomarkers"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":18,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,11,15]]},"published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db23-0277","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.24550600.v2","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.24550600.v1","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.24550600","asserted-by":"object"}]},"ISSN":["0012-1797"],"issn-type":[{"value":"0012-1797","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}