Understanding Diabetic Cardiomyopathy: Insulin Resistance and Beyond

Overview

Journal Heart Int

Date 2025 Jan 31

PMID 39885933

Authors

Aditya John Binu

Nitin Kapoor

Affiliations

Soon will be listed here.

Abstract

Diabetic cardiomyopathy (DC) is a syndrome of heart failure occurring in patients with diabetes mellitus (DM), independent of other risk factors. It is a relatively underdiagnosed condition with a prolonged subclinical phase. There is an abundance of studies put forward to explain the underlying pathogenic mechanisms observed in this condition. This review aims to summarize the evidence available in contemporary medical literature with regard to the molecular mechanisms, abnormalities in signalling and metabolism and structural and functional abnormalities manifesting as DC. We conducted a literature search using the terms 'diabetic cardiomyopathy', 'heart failure AND Diabetes mellitus', 'Cardiomyopathy AND Diabetes mellitus'. We searched the reference lists of included studies and relevant systematic reviews. In this review, we elucidate all the mechanisms that have been postulated to have a role in the pathogenesis of DC, in addition to insulin resistance, such as inflammation, renin-angiotensin-aldosterone system activation and deranged protein homeostasis. DC is an underrecognized cardiac complication of DM. A comprehensive knowledge of all the pathways and mediators will aid in the development of diagnostic and prognostic markers, screening protocols and novel management strategies.

References

Lee T, Bai K, Lee T, Chao T, Kao Y, Chen Y . PPARs modulate cardiac metabolism and mitochondrial function in diabetes. J Biomed Sci. 2017; 24(1):5. PMC: 5223385. DOI: 10.1186/s12929-016-0309-5. View

Kosiborod M, Petrie M, Borlaug B, Butler J, Davies M, Hovingh G . Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. 2024; 390(15):1394-1407. DOI: 10.1056/NEJMoa2313917. View

Jia G, Habibi J, Demarco V, Martinez-Lemus L, Ma L, Whaley-Connell A . Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac Diastolic Dysfunction in Females. Hypertension. 2015; 66(6):1159-1167. PMC: 4644106. DOI: 10.1161/HYPERTENSIONAHA.115.06015. View

Marso S, Holst A, Vilsboll T . Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2017; 376(9):891-2. DOI: 10.1056/NEJMc1615712. View

Finck B, Lehman J, Leone T, Welch M, Bennett M, Kovacs A . The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. 2002; 109(1):121-30. PMC: 150824. DOI: 10.1172/JCI14080. View

Kannel W, Hjortland M, CASTELLI W . Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974; 34(1):29-34. DOI: 10.1016/0002-9149(74)90089-7. View

Holman R, Sourij H, Califf R . Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes. Lancet. 2014; 383(9933):2008-17. DOI: 10.1016/S0140-6736(14)60794-7. View

Ferraro E, Giammarioli A, Caldarola S, Lista P, Feraco A, Tinari A . The metabolic modulator trimetazidine triggers autophagy and counteracts stress-induced atrophy in skeletal muscle myotubes. FEBS J. 2013; 280(20):5094-108. DOI: 10.1111/febs.12484. View

Stolen T, Hoydal M, Kemi O, Catalucci D, Ceci M, Aasum E . Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circ Res. 2009; 105(6):527-36. DOI: 10.1161/CIRCRESAHA.109.199810. View

10.

Sacre J, Franjic B, Jellis C, Jenkins C, Coombes J, Marwick T . Association of cardiac autonomic neuropathy with subclinical myocardial dysfunction in type 2 diabetes. JACC Cardiovasc Imaging. 2010; 3(12):1207-15. DOI: 10.1016/j.jcmg.2010.09.014. View

11.

Penpargkul S, Fein F, SONNENBLICK E, Scheuer J . Depressed cardiac sarcoplasmic reticular function from diabetic rats. J Mol Cell Cardiol. 1981; 13(3):303-9. DOI: 10.1016/0022-2828(81)90318-7. View

12.

Samuel V . Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab. 2010; 22(2):60-5. DOI: 10.1016/j.tem.2010.10.003. View

13.

Zhou Y, Marlen K, Palma J, Schweitzer A, Reilly L, Gregoire F . Overexpression of repressive cAMP response element modulators in high glucose and fatty acid-treated rat islets. A common mechanism for glucose toxicity and lipotoxicity?. J Biol Chem. 2003; 278(51):51316-23. DOI: 10.1074/jbc.M307972200. View

14.

Baudrand R, Gupta N, Garza A, Vaidya A, Leopold J, Hopkins P . Caveolin 1 Modulates Aldosterone-Mediated Pathways of Glucose and Lipid Homeostasis. J Am Heart Assoc. 2016; 5(10). PMC: 5121487. DOI: 10.1161/JAHA.116.003845. View

15.

Juurlink D, Gomes T, Lipscombe L, Austin P, Hux J, Mamdani M . Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ. 2009; 339:b2942. PMC: 2728804. DOI: 10.1136/bmj.b2942. View

16.

Wiviott S, Raz I, Bonaca M, Mosenzon O, Kato E, Cahn A . Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2018; 380(4):347-357. DOI: 10.1056/NEJMoa1812389. View

17.

Anderson E, Kypson A, Rodriguez E, Anderson C, Lehr E, Neufer P . Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. J Am Coll Cardiol. 2009; 54(20):1891-8. PMC: 2800130. DOI: 10.1016/j.jacc.2009.07.031. View

18.

Eguchi K, Boden-Albala B, Jin Z, Rundek T, Sacco R, Homma S . Association between diabetes mellitus and left ventricular hypertrophy in a multiethnic population. Am J Cardiol. 2008; 101(12):1787-91. PMC: 2486269. DOI: 10.1016/j.amjcard.2008.02.082. View

19.

Shome J, Perera D, Plein S, Chiribiri A . Current perspectives in coronary microvascular dysfunction. Microcirculation. 2016; 24(1). DOI: 10.1111/micc.12340. View

20.

Uchimura K, Hayata M, Mizumoto T, Miyasato Y, Kakizoe Y, Morinaga J . The serine protease prostasin regulates hepatic insulin sensitivity by modulating TLR4 signalling. Nat Commun. 2014; 5:3428. PMC: 3959208. DOI: 10.1038/ncomms4428. View