{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:00:37Z","timestamp":1760551237093,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2017T039"],"award-info":[{"award-number":["2017T039"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3\u2010deoxyglucosone and their derived advanced glycation end products (AGEs), and increased <jats:sc>d<\/jats:sc>\u2010lactate, reflecting greater methylglyoxal flux.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3\u2010deoxyglucosone, free AGEs and <jats:sc>d<\/jats:sc>\u2010lactate using ultra\u2010performance liquid chromatography tandem mass\u2010spectrometry (UPLC\u2010MS\/MS) in the treatment arm receiving 300\u00a0mg irbesartan (<jats:italic>n<\/jats:italic>\u00a0=\u00a0121) and a placebo group (<jats:italic>n<\/jats:italic>\u00a0=\u00a0101) at baseline and after 1 and 2\u00a0years. Effect of treatment was analysed with repeated measurements ANOVA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a slight, but significant difference in baseline median methylglyoxal levels [placebo 1119 (907\u20131509) nmol\/l vs. irbesartan 300\u00a0mg 1053 (820\u20131427) nmol\/l], but no significant changes were observed in any of the plasma dicarbonyls over time in either group and there was no effect of irbesartan treatment on plasma free AGEs or <jats:sc>d<\/jats:sc>\u2010lactate levels at either 1 or 2\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Irbesartan treatment does not change plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3\u2010deoxyglucosone, free AGEs or <jats:sc>d<\/jats:sc>\u2010lactate in type 2 diabetes. This indicates that increased dicarbonyls in type 2 diabetes are not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No: #NCT00317915).<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.14405","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:57:26Z","timestamp":1600822646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Irbesartan treatment does not influence plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3\u2010deoxyglucosone in participants with type 2 diabetes and microalbuminuria: An IRMA2 sub\u2010study"],"prefix":"10.1111","volume":"38","author":[{"given":"M.","family":"Piazza","sequence":"first","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"},{"name":"Department of Medicine\u2010DIMED University of Padua  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. M. J.","family":"Hanssen","sequence":"additional","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Persson","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. L.","family":"Scheijen","sequence":"additional","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. P. H.","family":"van de Waarenburg","sequence":"additional","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. M. J.","family":"van Greevenbroek","sequence":"additional","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Hovind","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen Copenhagen Denmark"},{"name":"Clinical Physiology and Nuclear Medicine Bispebjerg Hospital Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. D. A.","family":"Stehouwer","sequence":"additional","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u2010H.","family":"Parving","sequence":"additional","affiliation":[{"name":"Medical Endocrinology University Hospital of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0190-2690","authenticated-orcid":false,"given":"C. G.","family":"Schalkwijk","sequence":"additional","affiliation":[{"name":"Internal Medicine Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000032549.36050.78"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy1201.100589"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011489"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2019"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1390"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db16-1578"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0159"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13201"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4328"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3088-5"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0316"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0552"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2012-0878"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/234812"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2017.03.019"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2605"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr102"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpt281"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.09225.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1722-z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.1.198"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.14405","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dme.14405","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.14405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T19:30:50Z","timestamp":1693337450000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.14405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,16]]},"references-count":24,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1111\/dme.14405"],"URL":"https:\/\/doi.org\/10.1111\/dme.14405","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"type":"print","value":"0742-3071"},{"type":"electronic","value":"1464-5491"}],"subject":[],"published":{"date-parts":[[2020,10,16]]},"assertion":[{"value":"2020-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14405"}}