{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T21:46:49Z","timestamp":1772833609298,"version":"3.50.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Diabetic cardiomyopathy (DCM) is one of the most essential cardiovascular complications in diabetic patients associated with glucose and lipid metabolism disorder, fibrosis, oxidative stress, and inflammation in cardiomyocytes. Despite increasing research on the molecular pathogenesis of DCM, it is still unclear whether metabolic pathways and alterations are probably involved in the development of DCM. This study aims to characterize the metabolites of DCM and to identify the relationship between metabolites and their biological processes or biological states through untargeted metabolic profiling. UPLC-MS\/MS was applied to profile plasma metabolites from 78 patients with diabetes (39 diabetes with DCM and 39 diabetes without DCM as controls). A total of 2,806 biochemical were detected. Compared to those of DM patients, 78 differential metabolites in the positive-ion mode were identified in DCM patients, including 33 up-regulated and 45 down-regulated metabolites; however, there were only six differential metabolites identified in the negative mode including four up-regulated and two down-regulated metabolites. Alterations of several serum metabolites, including lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the development of DCM. KEGG enrichment analysis showed that there were three signaling pathways (metabolic pathways, porphyrin, chlorophyll metabolism, and lysine degradation) that were changed in both negative- and positive-ion modes. Our results demonstrated that differential metabolites and lipids have specific effects on DCM. These results expanded our understanding of the metabolic characteristics of DCM and may provide a clue in the future investigation of reducing the incidence of DCM. Furthermore, the metabolites identified here may provide clues for clinical management and the development of effective drugs.<\/jats:p>","DOI":"10.3389\/fphys.2022.863347","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T07:20:40Z","timestamp":1652080840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Metabonomic Characteristics of Myocardial Diastolic Dysfunction in Type 2 Diabetic Cardiomyopathy Patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Mingyu","family":"Hao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiting","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangsheng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajie","family":"She","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dewen","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s12020-009-9243-6","article-title":"Serum Heart Type Fatty Acid Binding Protein Levels in Metabolic Syndrome","volume":"36","author":"Akbal","year":"2009","journal-title":"Endocr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.trsl.2021.03.010","article-title":"Pharmacological Regulation of Cytochrome P450 Metabolites of Arachidonic Acid Attenuates Cardiac Injury in Diabetic Rats","volume":"235","author":"Alaeddine","year":"2021","journal-title":"Translational Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.1093\/eurheartj\/eht108","article-title":"ESC Guidelines on Diabetes, Pre-diabetes, and Cardiovascular Diseases Developed in Collaboration with the EASD","volume":"34","author":"Authors\/Task Force","year":"2013","journal-title":"Eur. Heart J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1055\/s-2006-959596","article-title":"Feverfew and Vascular Smooth Muscle: Extracts from Fresh and Dried Plants Show Opposing Pharmacological Profiles, Dependent upon Sesquiterpene Lactone Content","volume":"59","author":"Barsby","year":"1993","journal-title":"Planta Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1021\/tx9902082","article-title":"Role of Quinones in Toxicology","volume":"13","author":"Bolton","year":"2000","journal-title":"Chem. Res. Toxicol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5341","DOI":"10.1210\/en.2005-0938","article-title":"Reduced Cardiac Efficiency and Altered Substrate Metabolism Precedes the Onset of Hyperglycemia and Contractile Dysfunction in Two Mouse Models of Insulin Resistance and Obesity","volume":"146","author":"Buchanan","year":"2005","journal-title":"Endocrinology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/s41467-020-20750-8","article-title":"An Integrative Multiomic Network Model Links Lipid Metabolism to Glucose Regulation in Coronary Artery Disease","volume":"12","author":"Cohain","year":"2021","journal-title":"Nat. Commun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.cardfail.2014.02.007","article-title":"The Prevalence of Diabetic Cardiomyopathy: a Population-Based Study in Olmsted County, Minnesota","volume":"20","author":"Dandamudi","year":"2014","journal-title":"J. Card. Fail."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4967","DOI":"10.3390\/ijms22094967","article-title":"Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity","volume":"22","author":"Darakjian","year":"2021","journal-title":"Ijms"},{"key":"B10","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/nchembio.1086","article-title":"An Enzyme-Trap Approach Allows Isolation of Intermediates in Cobalamin Biosynthesis","volume":"8","author":"Deery","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/978-3-030-01099-7_2","article-title":"Biomolecular Targets of Oxyprenylated Phenylpropanoids and Polyketides","volume":"108","author":"Fiorito","year":"2019","journal-title":"Prog. Chem. Org. Nat. Prod."},{"key":"B12","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.rce.2019.01.00910.1016\/j.rceng.2019.01.014","article-title":"Heart Failure and Diabetes: The Confrontation of Two Major Epidemics of the 21st century","volume":"220","author":"Formiga","year":"2020","journal-title":"Revista Cl\u00ednica Espa\u00f1ola (English Edition)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"865","DOI":"10.2174\/1573399811666150615150235","article-title":"AMPK as a New Attractive Therapeutic Target for Disease Prevention: The Role of Dietary Compounds AMPK and Disease Prevention","volume":"17","author":"Gasparrini","year":"2016","journal-title":"Cdt"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/1310265","article-title":"Diabetic Cardiomyopathy: Current Approach and Potential Diagnostic and Therapeutic Targets","volume":"2017","author":"Gilca","year":"2017","journal-title":"J. Diabetes Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jdiacomp.2016.08.025","article-title":"Vitamin B12 Deficiency Is Associated with Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes","volume":"31","author":"Hansen","year":"2017","journal-title":"J. Diabetes its Complications"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1016\/j.ijcard.2007.07.057","article-title":"Serum Carboxy-Terminal Propeptide of Type I Procollagen (PIP) Is a Marker of Diastolic Dysfunction in Patients with Early Type 2 Diabetes Mellitus","volume":"122","author":"Ihm","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nrendo.2015.216","article-title":"Insulin Resistance and Hyperinsulinaemia in Diabetic Cardiomyopathy","volume":"12","author":"Jia","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00125-017-4390-4","article-title":"Diabetic Cardiomyopathy: a Hyperglycaemia- and Insulin-Resistance-Induced Heart Disease","volume":"61","author":"Jia","year":"2018","journal-title":"Diabetologia"},{"key":"B19","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3389\/fphar.2017.00749","article-title":"Salidroside, A Natural Antioxidant, Improves \u03b2-Cell Survival and Function via Activating AMPK Pathway","volume":"8","author":"Ju","year":"2017","journal-title":"Front. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.3390\/ijms21062187","article-title":"Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases","volume":"21","author":"Kim","year":"2020","journal-title":"Ijms"},{"key":"B21","doi-asserted-by":"publisher","first-page":"H958","DOI":"10.1152\/ajpheart.00956.2015","article-title":"Left Ventricular Pressure-Volume Measurements and Myocardial Gene Expression Profile in Type 2 Diabetic Goto-Kakizaki Rats","volume":"311","author":"Korkmaz-Ic\u00f6z","year":"2016","journal-title":"Am. J. Physiology-Heart Circulatory Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.7150\/thno.40735","article-title":"Distinct Cardiac Energy Metabolism and Oxidative Stress Adaptations between Obese and Non-obese Type 2 Diabetes Mellitus","volume":"10","author":"Li","year":"2020","journal-title":"Theranostics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s12933-015-0288-y","article-title":"Circulating Interleukin-1\u03b2 Promotes Endoplasmic Reticulum Stress-Induced Myocytes Apoptosis in Diabetic Cardiomyopathy via Interleukin-1 Receptor-Associated Kinase-2","volume":"14","author":"Liu","year":"2015","journal-title":"Cardiovasc. Diabetol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3390\/jcm9041105","article-title":"Galectin-3 Is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes","volume":"9","author":"Lorenzo-Almor\u00f3s","year":"2020","journal-title":"Jcm"},{"key":"B25","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3389\/fendo.2017.00072","article-title":"Diabetic Cardiomyopathy: An Immunometabolic Perspective","volume":"8","author":"Mishra","year":"2017","journal-title":"Front. Endocrinol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3661","DOI":"10.1210\/en.2017-00294","article-title":"Aldose Reductase Mediates NLRP3 Inflammasome-Initiated Innate Immune Response in Hyperglycemia-Induced Thp1 Monocytes and Male Mice","volume":"158","author":"Pal","year":"2017","journal-title":"Endocrinology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"146","DOI":"10.4093\/dmj.2020.0282","article-title":"Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes","volume":"45","author":"Park","year":"2021","journal-title":"Diabetes Metab. J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1002\/biof.1438","article-title":"Chlorophyllin Supplementation Modulates Hyperglycemia-Induced Oxidative Stress and Apoptosis in Liver of Streptozotocin-Administered Mice","volume":"44","author":"Patar","year":"2018","journal-title":"Biofactors"},{"key":"B29","doi-asserted-by":"publisher","first-page":"3887","DOI":"10.2337\/db13-0095","article-title":"Myocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by P38\u03b1 MAPK during Insulin Resistance","volume":"62","author":"Qi","year":"2013","journal-title":"Diabetes"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1038\/s41467-020-16116-9","article-title":"A PKB-SPEG Signaling Nexus Links Insulin Resistance with Diabetic Cardiomyopathy by Regulating Calcium Homeostasis","volume":"11","author":"Quan","year":"2020","journal-title":"Nat. Commun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/1475-2840-9-89","article-title":"Early Diagnosis of Left Ventricular Diastolic Dysfunction in Diabetic Patients: a Possible Role for Natriuretic Peptides","volume":"9","author":"Romano","year":"2010","journal-title":"Cardiovasc. Diabetol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/0002-9149(72)90595-4","article-title":"New Type of Cardiomyopathy Associated with Diabetic Glomerulosclerosis","volume":"30","author":"Rubler","year":"1972","journal-title":"Am. J. Cardiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"19012","DOI":"10.1038\/s41598-021-98227-x","article-title":"Galectin-3 for Prediction of Cardiac Function Compared to NT-proBNP in Individuals with Prediabetes and Type 2 Diabetes Mellitus","volume":"11","author":"Schmitt","year":"2021","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"H1609","DOI":"10.1152\/ajpheart.00949.2007","article-title":"Metoprolol Improves Cardiac Function and Modulates Cardiac Metabolism in the Streptozotocin-Diabetic Rat","volume":"294","author":"Sharma","year":"2008","journal-title":"Am. J. Physiology-Heart Circulatory Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"161","DOI":"10.7150\/ijms.14141","article-title":"Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population","volume":"13","author":"Shaver","year":"2016","journal-title":"Int. J. Med. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/j.1440-1681.2012.05726.x","article-title":"FT23, an Orally Active Antifibrotic Compound, Attenuates Structural and Functional Abnormalities in an Experimental Model of Diabetic Cardiomyopathy","volume":"39","author":"Tan","year":"2012","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41569-020-0339-2","article-title":"Mechanisms of Diabetic Cardiomyopathy and Potential Therapeutic Strategies: Preclinical and Clinical Evidence","volume":"17","author":"Tan","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.jep.2012.05.063","article-title":"Rhodiola Crenulata Root Ameliorates Derangements of Glucose and Lipid Metabolism in a Rat Model of the Metabolic Syndrome and Type 2 Diabetes","volume":"142","author":"Wang","year":"2012","journal-title":"J. Ethnopharmacology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"25399","DOI":"10.1038\/srep25399","article-title":"Salidroside Improves Glucose Homeostasis in Obese Mice by Repressing Inflammation in white Adipose Tissues and Improving Leptin Sensitivity in Hypothalamus","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3389\/fphys.2016.00125","article-title":"New Molecular Insights of Insulin in Diabetic Cardiomyopathy","volume":"7","author":"Westermeier","year":"2016","journal-title":"Front. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12933-019-0811-7","article-title":"MiR-30c\/PGC-1\u03b2 Protects against Diabetic Cardiomyopathy via PPAR\u03b1","volume":"18","author":"Yin","year":"2019","journal-title":"Cardiovasc. Diabetol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.863347\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T11:32:40Z","timestamp":1652700760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.863347\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,9]]},"references-count":41,"alternative-id":["10.3389\/fphys.2022.863347"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.863347","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,9]]},"article-number":"863347"}}