{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:09:43Z","timestamp":1776128983147,"version":"3.50.1"},"reference-count":153,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,9]],"date-time":"2019-03-09T00:00:00Z","timestamp":1552089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter stages of the disease. In this article we propose the potential pathophysiological mechanisms responsible for myocardial hypertrophy and increased myocardial stiffness leading to diastolic dysfunction in this specific entity. According to our model, increased myocardial stiffness results from both cellular and extracellular matrix stiffness as well as cell\u2013matrix interactions. Increased intrinsic cardiomyocyte stiffness is probably the most important contributor to myocardial stiffness. It results from the impairment in cardiomyocyte cytoskeleton. Several other mechanisms, specifically affected by diabetes, seem to also be significantly involved in myocardial stiffening, i.e., impairment in the myocardial nitric oxide (NO) pathway, coronary microvascular dysfunction, increased inflammation and oxidative stress, and myocardial sodium glucose cotransporter-2 (SGLT-2)-mediated effects. Better understanding of the complex pathophysiology of DCM suggests the possible value of drugs targeting the listed mechanisms. Antidiabetic drugs, NO-stimulating agents, anti-inflammatory agents, and SGLT-2 inhibitors are emerging as potential treatment options for DCM.<\/jats:p>","DOI":"10.3390\/ijms20051197","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T03:49:31Z","timestamp":1552362571000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Molecular Mechanisms Responsible for Diastolic Dysfunction in Diabetes Mellitus Patients"],"prefix":"10.3390","volume":"20","author":[{"given":"Jovana","family":"Nikolajevi\u0107 Star\u010devi\u0107","sequence":"first","affiliation":[{"name":"Department of Vascular Diseases, University Medical Centre Ljubljana, Zalo\u0161ka cesta 7; SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-8922","authenticated-orcid":false,"given":"Miodrag","family":"Jani\u0107","sequence":"additional","affiliation":[{"name":"Department of Vascular Diseases, University Medical Centre Ljubljana, Zalo\u0161ka cesta 7; SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi\u0161o","family":"\u0160abovi\u010d","sequence":"additional","affiliation":[{"name":"Department of Vascular Diseases, University Medical Centre Ljubljana, Zalo\u0161ka cesta 7; SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1007\/s00125-012-2579-0","article-title":"High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes","volume":"55","author":"Rutten","year":"2012","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.2337\/diacare.28.3.612","article-title":"The association between glucose abnormalities and heart failure in the population-based reykjavik study","volume":"28","author":"Thrainsdottir","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0002-9149(74)90089-7","article-title":"Role of diabetes in congestive heart failure: The framingham study","volume":"34","author":"Kannel","year":"1974","journal-title":"Am. 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