An Insight into the Pathogenesis of Diabetic Cardiomyopathy Along with
the Novel Potential Therapeutic Approaches

Himangi      Vig; Ravinandan      AP; Hunsur   Nagendra   Vishwas; Sachin      Tyagi; Shruti      Rathore; Ankita      Wal; Pranay      Wal
doi:10.2174/1573399819666230502110511
Abstract

Background: The existence of aberrant myocardial activity and function in the exclusion of those other cardiovascular events, such as atherosclerosis, hypertension, and severe valve disease, is known as diabetic cardiomyopathy. Diabetes patients are much more prone to death from cardiovascular illnesses than from any other cause, and they also have a 2–5 fold higher likelihood of acquiring cardiac failure and other complications.
Objective: In this review, the pathophysiology of diabetic cardiomyopathy is discussed, with an emphasis on the molecular and cellular irregularities that arise as the condition progresses, as well as existing and prospective future treatments.
Method: The literature for this topic was researched utilizing Google Scholar as a search engine. Before compiling the review article, several research and review publications from various publishers, including Bentham Science, Nature, Frontiers, and Elsevier, were investigated.
Result: The abnormal cardiac remodelling, marked by left ventricular concentric thickening and interstitial fibrosis contributing to diastolic impairment, is mediated by hyperglycemia, and insulin sensitivity. The pathophysiology of diabetic cardiomyopathy has been linked to altered biochemical parameters, decreased calcium regulation and energy production, enhanced oxidative damage and inflammation, and a build-up of advanced glycation end products.
Conclusion: Antihyperglycemic medications are essential for managing diabetes because they successfully lower microvascular problems. GLP-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors have now been proven to benefit heart health by having a direct impact on the cardiomyocyte. To cure and avoid diabetic cardiomyopathy new medicines are being researched, including miRNA and stem cell therapies.
Keywords: Diabetic cardiomyopathy, miRNA, Stem cell therapies, GLP-1 receptor agonists, Sodium-glucose cotransporter 2 inhibitors, Renin-angiotensin–aldosterone system, Microcirculation Impairment .
[1]
Zheng J, Cheng J, Zheng S, Feng Q, Xiao X. Curcumin, a polyphenolic curcuminoid with its protective effects and molecular mechanisms in diabetes and diabetic cardiomyopathy. Front Pharmacol  2018; 9: 472.
 [http://dx.doi.org/10.3389/fphar.2018.00472] [PMID: 29867479]

[2]
Nelson MAM, Builta ZJ, Monroe TB, Doorn JA, Anderson EJ. Biochemical characterization of the catecholaldehyde reactivity of l-carnosine and its therapeutic potential in human myocardium. Amino Acids  2019; 51(1): 97-102.
 [http://dx.doi.org/10.1007/s00726-018-2647-y] [PMID: 30191330]

[3]
Nelson MAM, Efird JT, Kew KA, et al. Enhanced catecholamine flux and impaired carbonyl metabolism disrupt cardiac mitochondrial oxidative phosphorylation in diabetes patients. Antioxid Redox Signal  2021; 35(4): 235-51.
 [http://dx.doi.org/10.1089/ars.2020.8122] [PMID: 33066717]

[4]
Ritchie RH, Abel ED. Basic mechanisms of diabetic heart disease. Circ Res  2020; 126(11): 1501-25.
 [http://dx.doi.org/10.1161/CIRCRESAHA.120.315913] [PMID: 32437308]

[5]
Korkmaz-Icöz S, Al Said S, Radovits T, et al. Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway. Cardiovasc Diabetol  2016; 15(1): 75.
 [http://dx.doi.org/10.1186/s12933-016-0383-8] [PMID: 27153943]

[6]
Roy D, Modi A, Khokhar M, et al. Microrna 21 emerging role in diabetic complications: A critical update. Curr Diabetes Rev  2021; 17(2): 122-35.
 [http://dx.doi.org/10.2174/18756417MTA2tMzAmw] [PMID: 32359340]

[7]
Al Hroob AM, Abukhalil MH, Hussein OE, Mahmoud AM. Pathophysiological mechanisms of diabetic cardiomyopathy and the therapeutic potential of epigallocatechin-3-gallate. Biomed Pharmacother  2019; 109: 2155-72.
 [http://dx.doi.org/10.1016/j.biopha.2018.11.086] [PMID: 30551473]

[8]
Thomas MC. Type 2 diabetes and heart failure: Challenges and solutions. Curr Cardiol Rev  2016; 12(3): 249-55.
 [http://dx.doi.org/10.2174/1573403X12666160606120254] [PMID: 27280301]

[9]
Andreadi A, Bellia A, Di Daniele N, et al. The molecular link between oxidative stress, insulin resistance, and type 2 diabetes: A target for new therapies against cardiovascular diseases. Curr Opin Pharmacol  2022; 62: 85-96.
 [http://dx.doi.org/10.1016/j.coph.2021.11.010] [PMID: 34959126]

[10]
Miki T, Yuda S, Kouzu H, Miura T. Diabetic cardiomyopathy: Pathophysiology and clinical features. Heart Fail Rev  2013; 18(2): 149-66.
 [http://dx.doi.org/10.1007/s10741-012-9313-3] [PMID: 22453289]

[11]
Cubillos-Angulo JM, Vinhaes CL, Fukutani ER, et al. In silico transcriptional analysis of mRNA and miRNA reveals unique biosignatures that characterizes different types of diabetes. PLoS One  2020; 15(9): e0239061.
 [http://dx.doi.org/10.1371/journal.pone.0239061] [PMID: 32956382]

[12]
Nair N, Gongora E. Oxidative stress and cardiovascular aging: Interaction between NRF-2 and ADMA. Curr Cardiol Rev  2017; 13(3): 183-8.
 [PMID: 28215178]

[13]
Rasolabadi M, Khaledi S, Ardalan M, Kalhor M, Penjvini S, Gharib A. Diabetes research in Iran: A scientometric analysis of publications output. Acta Inform Med  2015; 23(3): 160-4.
 [http://dx.doi.org/10.5455/aim.2015.23.160-164] [PMID: 26236083]

[14]
Scheen AJ. Pharmacotherapy of ‘treatment resistant’ type 2 diabetes. Expert Opin Pharmacother  2017; 18(5): 503-15.
 [http://dx.doi.org/10.1080/14656566.2017.1297424] [PMID: 28276972]

[15]
Amdare N, Purcell AW, DiLorenzo TP. Noncontiguous T cell epitopes in autoimmune diabetes: From mice to men and back again. J Biol Chem  2021; 297(1): 100827.
 [http://dx.doi.org/10.1016/j.jbc.2021.100827] [PMID: 34044020]

[16]
Hölscher M, Bode C, Bugger H. Diabetic cardiomyopathy: Does the type of diabetes matter? Int J Mol Sci  2016; 17(12): 2136.
 [http://dx.doi.org/10.3390/ijms17122136] [PMID: 27999359]

[17]
Xu CR, Fang QJ. Inhibiting glucose metabolism by miR-34a and miR-125b protects against hyperglycemia-induced cardiomyocyte cell death. Arq Bras Cardiol  2021; 116(3): 415-22.
 [http://dx.doi.org/10.36660/abc.20190529] [PMID: 33909769]

[18]
Tarquini R, Pala L, Brancati S, et al. Clinical approach to diabetic cardiomyopathy: A review of human studies. Curr Med Chem  2018; 25(13): 1510-24.
 [http://dx.doi.org/10.2174/0929867324666170705111356] [PMID: 28685679]

[19]
Voulgari C, Pagoni S, Tesfaye S, Tentolouris N. The spatial QRS-T angle: Implications in clinical practice. Curr Cardiol Rev  2013; 9(3): 197-210.
 [http://dx.doi.org/10.2174/1573403X113099990031] [PMID: 23909632]

[20]
Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev  2013; 93(1): 137-88.
 [http://dx.doi.org/10.1152/physrev.00045.2011] [PMID: 23303908]

[21]
Chrysohoou C, Pitsavos C, Metallinos G, et al. Cross-sectional relationship of a Mediterranean type diet to diastolic heart function in chronic heart failure patients. Heart Vessels  2012; 27(6): 576-84.
 [http://dx.doi.org/10.1007/s00380-011-0190-9] [PMID: 21947607]

[22]
Angelis A, Chrysohoou C, Tzorovili E, et al. The Mediterranean diet benefit on cardiovascular hemodynamics and erectile function in chronic heart failure male patients by decoding central and peripheral vessel rheology. Nutrients  2020; 13(1): 108.
 [http://dx.doi.org/10.3390/nu13010108] [PMID: 33396861]

[23]
Weng L, Li L, Zhao K, et al. Non-invasive local acoustic therapy ameliorates diabetic heart fibrosis by suppressing ACE-mediated oxidative stress and inflammation in cardiac fibroblasts. Cardiovasc Drugs Ther  2022; 36(3): 413-24.
 [http://dx.doi.org/10.1007/s10557-021-07297-6] [PMID: 35156147]

[24]
Huynh K, Bernardo BC, McMullen JR, Ritchie RH. Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther  2014; 142(3): 375-415.
 [http://dx.doi.org/10.1016/j.pharmthera.2014.01.003] [PMID: 24462787]

[25]
Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol  2016; 12(3): 144-53.
 [http://dx.doi.org/10.1038/nrendo.2015.216] [PMID: 26678809]

[26]
Adeghate E, Singh J. Structural changes in the myocardium during diabetes-induced cardiomyopathy. Heart Fail Rev  2014; 19(1): 15-23.
 [http://dx.doi.org/10.1007/s10741-013-9388-5] [PMID: 23467937]

[27]
Paolillo S, Marsico F, Prastaro M, et al. Diabetic cardiomyopathy. Heart Fail Clin  2019; 15(3): 341-7.
 [http://dx.doi.org/10.1016/j.hfc.2019.02.003] [PMID: 31079692]

[28]
Mishra S, Kass DA. Cellular and molecular pathobiology of heart failure with preserved ejection fraction. Nat Rev Cardiol  2021; 18(6): 400-23.
 [http://dx.doi.org/10.1038/s41569-020-00480-6] [PMID: 33432192]

[29]
Tsigkou V, Oikonomou E, Anastasiou A, et al. Molecular mechanisms and therapeutic implications of endothelial dysfunction in patients with heart failure. Int J Mol Sci  2023; 24(5): 4321.
 [http://dx.doi.org/10.3390/ijms24054321] [PMID: 36901752]

[30]
Liu Q, Wang S, Cai L. Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage. J Diabetes Investig  2014; 5(6): 623-34.
 [http://dx.doi.org/10.1111/jdi.12250] [PMID: 25422760]

[31]
Siriwardena K, MacKay N, Levandovskiy V, et al. Mitochondrial citrate synthase crystals: Novel finding in Sengers syndrome caused by acylglycerol kinase (AGK) mutations. Mol Genet Metab  2013; 108(1): 40-50.
 [http://dx.doi.org/10.1016/j.ymgme.2012.11.282] [PMID: 23266196]

[32]
Zhang X, Chen C. A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy. Endocrine  2012; 41(3): 398-409.
 [http://dx.doi.org/10.1007/s12020-012-9623-1] [PMID: 22322947]

[33]
Brown DI, Griendling KK. Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res  2015; 116(3): 531-49.
 [http://dx.doi.org/10.1161/CIRCRESAHA.116.303584] [PMID: 25634975]

[34]
Rossino MG, Dal Monte M, Casini G. Relationships between neurodegeneration and vascular damage in diabetic retinopathy. Front Neurosci  2019; 13: 1172.
 [http://dx.doi.org/10.3389/fnins.2019.01172] [PMID: 31787868]

[35]
Gadjeva V, Goycheva P, Nikolova G, Zheleva A. Influence of glycemic control on some real-time biomarkers of free radical formation in type 2 diabetic patients: An EPR study. Adv Clin Exp Med  2017; 26(8): 1237-43.
 [http://dx.doi.org/10.17219/acem/68988] [PMID: 29264881]

[36]
Dhalla NS, Shah AK, Tappia PS. Role of oxidative stress in metabolic and subcellular abnormalities in diabetic cardiomyopathy. Int J Mol Sci  2020; 21(7): 2413.
 [http://dx.doi.org/10.3390/ijms21072413] [PMID: 32244448]

[37]
Dhalla NS, Takeda N, Rodriguez-Leyva D, Elimban V. Mechanisms of subcellular remodeling in heart failure due to diabetes. Heart Fail Rev  2014; 19(1): 87-99.
 [http://dx.doi.org/10.1007/s10741-013-9385-8] [PMID: 23436108]

[38]
Adameova A, Dhalla NS. Role of microangiopathy in diabetic cardiomyopathy. Heart Fail Rev  2014; 19(1): 25-33.
 [http://dx.doi.org/10.1007/s10741-013-9378-7] [PMID: 23456446]

[39]
Cas A, Spigoni V, Ridolfi V, Metra M. Diabetes and chronic heart failure: From diabetic cardiomyopathy to therapeutic approach. Endocr Metab Immune Disord Drug Targets  2013; 13(1): 38-50.
 [http://dx.doi.org/10.2174/1871530311313010006] [PMID: 23369136]

[40]
LaRocca TJ, Fabris F, Chen J, et al. Na + /Ca 2+ exchanger-1 protects against systolic failure in the Akita ins2 model of diabetic cardiomyopathy via a CXCR4/NF-κB pathway. Am J Physiol Heart Circ Physiol  2012; 303(3): H353-67.
 [http://dx.doi.org/10.1152/ajpheart.01198.2011] [PMID: 22610174]

[41]
Tian J, Zhao Y, Liu Y, Liu Y, Chen K, Lyu S. Roles and mechanisms of herbal medicine for diabetic cardiomyopathy: Current status and perspective. Oxid Med Cell Longev  2017; 2017: 1-15.
 [http://dx.doi.org/10.1155/2017/8214541] [PMID: 29204251]

[42]
Yan D, Luo X, Li Y, et al. Effects of advanced glycation end products on calcium handling in cardiomyocytes. Cardiology  2014; 129(2): 75-83.
 [http://dx.doi.org/10.1159/000364779] [PMID: 25138529]

[43]
Ng KM, Lau YM, Dhandhania V, et al. Empagliflozin ammeliorates high glucose induced-cardiac dysfuntion in human iPSC-derived cardiomyocytes. Sci Rep  2018; 8(1): 14872.
 [http://dx.doi.org/10.1038/s41598-018-33293-2] [PMID: 30291295]

[44]
Xu X, Kobayashi S, Chen K, et al. Diminished autophagy limits cardiac injury in mouse models of type 1 diabetes. J Biol Chem  2013; 288(25): 18077-92.
 [http://dx.doi.org/10.1074/jbc.M113.474650] [PMID: 23658055]

[45]
Mihanfar A, Akbarzadeh M, Ghazizadeh Darband S, Sadighparvar S, Majidinia M. SIRT1: A promising therapeutic target in type 2 diabetes mellitus. Arch Physiol Biochem  2021; 2021: 1-16.
 [http://dx.doi.org/10.1080/13813455.2021.1956976] [PMID: 34379994]

[46]
Ni R, Cao T, Xiong S, et al. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy. Free Radic Biol Med  2016; 90: 12-23.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.013] [PMID: 26577173]

[47]
Zhang N, Yang Z, Xiang SZ, et al. Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy. Mol Cell Biochem  2016; 417(1-2): 87-96.
 [http://dx.doi.org/10.1007/s11010-016-2716-z] [PMID: 27160937]

[48]
Palomer X, Pizarro-Delgado J, Vázquez-Carrera M. Emerging actors in diabetic cardiomyopathy: heartbreaker biomarkers or therapeutic targets? Trends Pharmacol Sci  2018; 39(5): 452-67.
 [http://dx.doi.org/10.1016/j.tips.2018.02.010] [PMID: 29605388]

[49]
Khan S, Kamal MA. Can wogonin be used in controlling diabetic cardiomyopathy? Curr Pharm Des  2019; 25(19): 2171-7.
 [http://dx.doi.org/10.2174/1381612825666190708173108] [PMID: 31298148]

[50]
Kotturu SK, Uddandrao VVS, Ghosh S, Parim B. Bioactive compounds in diabetic cardiomyopathy: current approaches and potential diagnostic and therapeutic targets. Cardiovasc Hematol Agents Med Chem  2021; 19(2): 118-30.
 [http://dx.doi.org/10.2174/1871525718666200421114801] [PMID: 32316902]

[51]
Lerner Y, Hanout W, Ben-Uliel SF, Gani S, Leshem MP, Qvit N. Natriuretic peptides as the basis of peptide drug discovery for cardiovascular diseases. Curr Top Med Chem  2020; 20(32): 2904-21.
 [http://dx.doi.org/10.2174/1568026620666201013154326] [PMID: 33050863]

[52]
Li X, Du N, Zhang Q, et al. MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy. Cell Death Dis  2014; 5(10): e1479.
 [http://dx.doi.org/10.1038/cddis.2014.430] [PMID: 25341033]

[53]
Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Investig  2013; 4(1): 4-18.
 [http://dx.doi.org/10.1111/jdi.12042] [PMID: 23550085]

[54]
Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia  2014; 57(4): 660-71.
 [http://dx.doi.org/10.1007/s00125-014-3171-6] [PMID: 24477973]

[55]
Yang GK, Maahs DM, Perkins BA, Cherney DZI. Renal hyperfiltration and systemic blood pressure in patients with uncomplicated type 1 diabetes mellitus. PLoS One  2013; 8(7): e68908.
 [http://dx.doi.org/10.1371/journal.pone.0068908] [PMID: 23861950]

[56]
Zamir I, Stoltz Sjöström E, Edstedt Bonamy AK, Mohlkert LA, Norman M, Domellöf M. Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm. Pediatr Res  2019; 86(1): 115-21.
 [http://dx.doi.org/10.1038/s41390-019-0341-8] [PMID: 30776793]

[57]
Li Q, Park K, Li C, et al. Induction of vascular insulin resistance and endothelin-1 expression and acceleration of atherosclerosis by the overexpression of protein kinase C-β isoform in the endothelium. Circ Res  2013; 113(4): 418-27.
 [http://dx.doi.org/10.1161/CIRCRESAHA.113.301074] [PMID: 23759514]

[58]
Sutton G, Pugh D, Dhaun N. Developments in the role of endothelin-1 in atherosclerosis: A potential therapeutic target? Am J Hypertens  2019; 32(9): 813-5.
 [http://dx.doi.org/10.1093/ajh/hpz091] [PMID: 31145445]

[59]
Zhang J, Zhao WS, Wang X, Xu L, Yang XC. Palmitic acid increases endothelin-1 expression in vascular endothelial cells through the induction of endoplasmic reticulum stress and protein kinase C signaling. Cardiology  2018; 140(3): 133-40.
 [http://dx.doi.org/10.1159/000490093] [PMID: 29996135]

[60]
Andersson C, Gislason GH, Møgelvang R, et al. Importance and inter-relationship of tissue Doppler variables for predicting adverse outcomes in high-risk patients: An analysis of 388 diabetic patients referred for coronary angiography. Eur Heart J Cardiovasc Imaging  2012; 13(8): 643-9.
 [http://dx.doi.org/10.1093/ejechocard/jer297] [PMID: 22207342]

[61]
Hodzic A, Ribault V, Maragnes P, Milliez P, Saloux E, Labombarda F. Decreased regional left ventricular myocardial strain in type 1 diabetic children: A first sign of diabetic cardiomyopathy? J Transl Int Med  2016; 4(2): 81-7.
 [http://dx.doi.org/10.1515/jtim-2016-0025] [PMID: 28191526]

[62]
Viigimaa M, Sachinidis A, Toumpourleka M, Koutsampasopoulos K, Alliksoo S, Titma T. Macrovascular complications of type 2 diabetes mellitus. Curr Vasc Pharmacol  2020; 18(2): 110-6.
 [http://dx.doi.org/10.2174/1570161117666190405165151] [PMID: 30961498]

[63]
Soares Felício J, Cavalcante Koury C, Tavares Carvalho C, et al. Present insights on cardiomyopathy in diabetic patients. Curr Diabetes Rev  2016; 12(4): 384-95.
 [http://dx.doi.org/10.2174/1573399812666150914120529] [PMID: 26364799]

[64]
Zhang Q, Liu Z, Du J, et al. Dermal exposure to nano-TiO2 induced cardiovascular toxicity through oxidative stress, inflammation and apoptosis. J Toxicol Sci  2019; 44(1): 35-45.
 [http://dx.doi.org/10.2131/jts.44.35] [PMID: 30626778]

[65]
Xia P, Liu Y, Cheng Z. Signaling pathways in cardiac myocyte apoptosis. BioMed Res Int  2016; 2016: 1-22.
 [http://dx.doi.org/10.1155/2016/9583268] [PMID: 28101515]

[66]
Teringova E, Tousek P. Apoptosis in ischemic heart disease. J Transl Med  2017; 15(1): 87.
 [http://dx.doi.org/10.1186/s12967-017-1191-y] [PMID: 28460644]

[67]
Dong Y, Chen H, Gao J, Liu Y, Li J, Wang J. Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease. J Mol Cell Cardiol  2019; 136: 27-41.
 [http://dx.doi.org/10.1016/j.yjmcc.2019.09.001] [PMID: 31505198]

[68]
Qin W, Liu G, Wang J, et al. Poly(ADP-ribose) polymerase 1 inhibition protects cardiomyocytes from inflammation and apoptosis in diabetic cardiomyopathy. Oncotarget  2016; 7(24): 35618-31.
 [http://dx.doi.org/10.18632/oncotarget.8343] [PMID: 27027354]

[69]
Arcopinto M, Bobbio E, Bossone E, et al. The GH/IGF-1 axis in chronic heart failure. Endocr Metab Immune Disord Drug Targets  2013; 13(1): 76-91.
 [http://dx.doi.org/10.2174/1871530311313010010] [PMID: 23369140]

[70]
Sharchil C, Vijay A, Ramachandran V, et al. Zebrafish: A model to study and understand the diabetic nephropathy and other microvascular complications of Type 2 diabetes mellitus. Vet Sci  2022; 9(7): 312.
 [http://dx.doi.org/10.3390/vetsci9070312] [PMID: 35878329]

[71]
Chen Y, Hua Y, Li X, Arslan IM, Zhang W, Meng G. Distinct types of cell death and the implication in diabetic cardiomyopathy. Front Pharmacol  2020; 11: 42.
 [http://dx.doi.org/10.3389/fphar.2020.00042] [PMID: 32116717]

[72]
Schlossarek S, Frey N, Carrier L. Ubiquitin-proteasome system and hereditary cardiomyopathies. J Mol Cell Cardiol  2014; 71: 25-31.
 [http://dx.doi.org/10.1016/j.yjmcc.2013.12.016] [PMID: 24380728]

[73]
Li J, Ma W, Yue G, et al. Cardiac proteasome functional insufficiency plays a pathogenic role in diabetic cardiomyopathy. J Mol Cell Cardiol  2017; 102: 53-60.
 [http://dx.doi.org/10.1016/j.yjmcc.2016.11.013] [PMID: 27913284]

[74]
Zhou Q, Lv D, Chen P, et al. MicroRNAs in diabetic cardiomyopathy and clinical perspectives. Front Genet  2014; 5: 185.
 [http://dx.doi.org/10.3389/fgene.2014.00185] [PMID: 25009554]

[75]
De Blasio MJ, Huynh N, Deo M, et al. Defining the progression of diabetic cardiomyopathy in a mouse model of type 1 diabetes. Front Physiol  2020; 11: 124.
 [http://dx.doi.org/10.3389/fphys.2020.00124] [PMID: 32153425]

[76]
Husain A, Alouffi S, Khanam A, et al. Non-inhibitory effects of the potent antioxidant from sp. on the glycation reaction. Rev Rom Med Lab  2022; 30(2): 199-213.

[77]
Tiwari N, Thakur AK, Kumar V, Dey A, Kumar V. Therapeutic targets for diabetes mellitus: An update. Clin Pharmacol Biopharm  2014; 3(1): 1.
 [http://dx.doi.org/10.4172/2167-065X.1000117]

[78]
Trang Nguyen ND, Le LT. Targeted proteins for diabetes drug design. Advances in Natural Sciences: Nanoscience and Nanotechnology  2012; 3(1): 013001.
 [http://dx.doi.org/10.1088/2043-6262/3/1/013001]

[79]
Maheshwari N, Karthikeyan C, Trivedi P, Moorthy NSHN. Recent advances in protein tyrosine phosphatase 1B targeted drug discovery for type II diabetes and obesity. Curr Drug Targets  2018; 19(5): 551-75.
 [http://dx.doi.org/10.2174/1389450118666170222143739] [PMID: 28228082]

[80]
Adeva-Andany MM, Martínez-Rodríguez J, González-Lucán M, Fernández-Fernández C, Castro-Quintela E. Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab Syndr  2019; 13(2): 1449-55.
 [http://dx.doi.org/10.1016/j.dsx.2019.02.023] [PMID: 31336505]

[81]
Fung CSC, Wan EYF, Wong CKH, Jiao F, Chan AKC. Effect of metformin monotherapy on cardiovascular diseases and mortality: A retrospective cohort study on Chinese type 2 diabetes mellitus patients. Cardiovasc Diabetol  2015; 14(1): 137.
 [http://dx.doi.org/10.1186/s12933-015-0304-2] [PMID: 26453464]

[82]
Li H, Lee J, He C, Zou MH, Xie Z. Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids. Am J Physiol Endocrinol Metab  2014; 306(2): E197-209.
 [http://dx.doi.org/10.1152/ajpendo.00202.2013] [PMID: 24302004]

[83]
Tokgozoglu L, Catapano AL. Can EPA evaporate plaques? Eur Heart J  2020; 41(40): 3933-5.
 [http://dx.doi.org/10.1093/eurheartj/ehaa750] [PMID: 33141163]

[84]
Li T, Jiang S, Yang Z, et al. Targeting the energy guardian AMPK: Another avenue for treating cardiomyopathy? Cell Mol Life Sci  2017; 74(8): 1413-29.
 [http://dx.doi.org/10.1007/s00018-016-2407-7] [PMID: 27815596]

[85]
Robinson E, Cassidy RS, Tate M, et al. Exendin-4 protects against post-myocardial infarction remodelling via specific actions on inflammation and the extracellular matrix. Basic Res Cardiol  2015; 110(2): 20.
 [http://dx.doi.org/10.1007/s00395-015-0476-7] [PMID: 25725809]

[86]
Jalleh RJ, Jones KL, Rayner CK, Marathe CS, Wu T, Horowitz M. Normal and disordered gastric emptying in diabetes: Recent insights into (patho)physiology, management and impact on glycaemic control. Diabetologia  2022; 65(12): 1981-93.
 [http://dx.doi.org/10.1007/s00125-022-05796-1] [PMID: 36194250]

[87]
Reed J, Kanamarlapudi V, Bain S. Mechanism of cardiovascular disease benefit of glucagon-like peptide 1 agonists. Cardiovasc Endocrinol Metab  2018; 7(1): 18-23.
 [PMID: 31646274]

[88]
Qi M, Zhou Q, Zeng W, et al. Analysis of long non-coding RNA expression of lymphatic endothelial cells in response to type 2 diabetes. Cell Physiol Biochem  2017; 41(2): 466-74.
 [http://dx.doi.org/10.1159/000456599] [PMID: 28214888]

[89]
Nickerson HD, Dutta S. Diabetic complications: Current challenges and opportunities. J Cardiovasc Transl Res  2012; 5(4): 375-9.
 [http://dx.doi.org/10.1007/s12265-012-9388-1] [PMID: 22752737]

[90]
Menikdiwela KR, Ramalingam L, Rasha F, et al. Autophagy in metabolic syndrome: Breaking the wheel by targeting the renin–angiotensin system. Cell Death Dis  2020; 11(2): 87.
 [http://dx.doi.org/10.1038/s41419-020-2275-9] [PMID: 32015340]

[91]
Adeghate EA, Kalász H, Al Jaberi S, Adeghate J, Tekes K. Tackling type 2 diabetes-associated cardiovascular and renal comorbidities: A key challenge for drug development. Expert Opin Investig Drugs  2021; 30(2): 85-93.
 [http://dx.doi.org/10.1080/13543784.2021.1865914] [PMID: 33327794]

[92]
Cao Z, Pan J, Sui X. Protective effects of HuangqiShengmai Yin on type 1 diabetes-induced cardiomyopathy by improving myocardial lipid metabolism. Evid Based Complement Alternat Med  2021; 2021: 1-13.

[93]
Westermann D, Becher PM, Lindner D, et al. Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo. Basic Res Cardiol  2012; 107(6): 308.
 [http://dx.doi.org/10.1007/s00395-012-0308-y] [PMID: 23117837]

[94]
Tsioufis C, Bafakis I, Kasiakogias A, Stefanadis C. The role of matrix metalloproteinases in diabetes mellitus. Curr Top Med Chem  2012; 12(10): 1159-65.
 [http://dx.doi.org/10.2174/1568026611208011159] [PMID: 22519446]

[95]
Ceriello A, Monnier L, Owens D. Glycaemic variability in diabetes: Clinical and therapeutic implications. Lancet Diabetes Endocrinol  2019; 7(3): 221-30.
 [http://dx.doi.org/10.1016/S2213-8587(18)30136-0] [PMID: 30115599]

[96]
Trachanas K, Sideris S, Aggeli C, et al. Diabetic cardiomyopathy: From pathophysiology to treatment. Hellenic J Cardiol  2014; 55(5): 411-21.
 [PMID: 25243440]

[97]
Chavali V, Tyagi SC, Mishra PK. Predictors and prevention of diabetic cardiomyopathy. Diabetes Metab Syndr Obes  2013; 6: 151-60.
 [PMID: 23610527]

[98]
von Lewinski D, Kolesnik E, Wallner M, Resl M, Sourij H. New antihyperglycemic drugs and heart failure: synopsis of basic and clinical data. BioMed Res Int  2017; 2017: 1-10.
 [http://dx.doi.org/10.1155/2017/1253425] [PMID: 28894748]

[99]
Wallner M, Eaton DM, von Lewinski D, Sourij H. Revisiting the diabetes-heart failure connection. Curr Diab Rep  2018; 18(12): 134.
 [http://dx.doi.org/10.1007/s11892-018-1116-z] [PMID: 30343339]

[100]
Zucker IH, Wang H, Schultz HD. GLP-1 (Glucagon-Like Peptide-1) Plays a role in carotid chemoreceptor-mediated sympathoexcitation and hypertension. Circ Res  2022; 130(5): 708-10.
 [http://dx.doi.org/10.1161/CIRCRESAHA.122.320799] [PMID: 35239402]

[101]
Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol  2012; 8(12): 728-42.
 [http://dx.doi.org/10.1038/nrendo.2012.140] [PMID: 22945360]

[102]
Khunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: A cohort study. Diabetes Care  2015; 38(2): 316-22.
 [http://dx.doi.org/10.2337/dc14-0920] [PMID: 25492401]

[103]
Lee AK, Warren B, Lee CJ, et al. The association of severe hypoglycemia with incident cardiovascular events and mortality in adults with type 2 diabetes. Diabetes Care  2018; 41(1): 104-11.
 [http://dx.doi.org/10.2337/dc17-1669] [PMID: 29127240]

[104]
Amiel SA, Aschner P, Childs B, et al. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: Epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol  2019; 7(5): 385-96.
 [http://dx.doi.org/10.1016/S2213-8587(18)30315-2] [PMID: 30926258]

[105]
Borghetti G, von Lewinski D, Eaton DM, Sourij H, Houser SR, Wallner M. Diabetic cardiomyopathy: Current and future therapies. Beyond glycemic control. Front Physiol  2018; 9: 1514.
 [http://dx.doi.org/10.3389/fphys.2018.01514] [PMID: 30425649]

[106]
Asleh R, Sheikh-Ahmad M, Briasoulis A, Kushwaha SS. The influence of anti-hyperglycemic drug therapy on cardiovascular and heart failure outcomes in patients with type 2 diabetes mellitus. Heart Fail Rev  2018; 23(3): 445-59.
 [http://dx.doi.org/10.1007/s10741-017-9666-8] [PMID: 29270818]

[107]
Anker SD, Butler J, Filippatos GS, et al. Evaluation of the effects of sodium–glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: Rationale for and design of the EMPEROR-Preserved Trial. Eur J Heart Fail  2019; 21(10): 1279-87.
 [http://dx.doi.org/10.1002/ejhf.1596] [PMID: 31523904]

[108]
Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: A state-of-the-art review. Diabetologia  2018; 61(10): 2108-17.
 [http://dx.doi.org/10.1007/s00125-018-4670-7] [PMID: 30132036]

[109]
Lan NSR, Fegan PG, Yeap BB, Dwivedi G. The effects of sodium glucose cotransporter 2 inhibitors on left ventricular function: Current evidence and future directions. ESC Heart Fail  2019; 6(5): 927-35.
 [http://dx.doi.org/10.1002/ehf2.12505] [PMID: 31400090]

[110]
Mukhopadhyay P, Sanyal D, Chatterjee P, Pandit K, Ghosh S. Different SGLT 2 inhibitors: Can they prevent death? Endocr Pract  2022; 28(8): 795-801.
 [http://dx.doi.org/10.1016/j.eprac.2022.05.005] [PMID: 35569736]

[111]
Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation  2017; 136(3): 249-59.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029190] [PMID: 28522450]

[112]
Mulvihill EE, Varin EM, Ussher JR, et al. Inhibition of dipeptidyl peptidase-4 impairs ventricular function and promotes cardiac fibrosis in high fat–fed diabetic mice. Diabetes  2016; 65(3): 742-54.
 [http://dx.doi.org/10.2337/db15-1224] [PMID: 26672095]

[113]
Zhang J, Chen Q, Zhong J, Liu C, Zheng B, Gong Q. DPP-4 inhibitors as potential candidates for antihypertensive therapy: improving vascular inflammation and assisting the action of traditional antihypertensive drugs. Front Immunol  2019; 10: 1050.
 [http://dx.doi.org/10.3389/fimmu.2019.01050] [PMID: 31134095]

[114]
Takahashi A, Asakura M, Ito S, et al. Dipeptidyl-peptidase IV inhibition improves pathophysiology of heart failure and increases survival rate in pressure-overloaded mice. Am J Physiol Heart Circ Physiol  2013; 304(10): H1361-9.
 [http://dx.doi.org/10.1152/ajpheart.00454.2012] [PMID: 23504176]

[115]
Bostick B, Habibi J, Ma L, et al. Dipeptidyl peptidase inhibition prevents diastolic dysfunction and reduces myocardial fibrosis in a Mouse model of Western diet induced obesity. Metabolism  2014; 63(8): 1000-11.
 [http://dx.doi.org/10.1016/j.metabol.2014.04.002] [PMID: 24933400]

[116]
Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: The CARMELINA randomized clinical trial. JAMA  2019; 321(1): 69-79.
 [http://dx.doi.org/10.1001/jama.2018.18269] [PMID: 30418475]

[117]
Pappachan JM, Varughese GI, Sriraman R, Arunagirinathan G. Diabetic cardiomyopathy: Pathophysiology, diagnostic evaluation and management. World J Diabetes  2013; 4(5): 177-89.
 [http://dx.doi.org/10.4239/wjd.v4.i5.177] [PMID: 24147202]

[118]
Filippatos TD, Elisaf MS. Are lower levels of LDL-cholesterol really better? Looking at the results of IMPROVE-IT: opinions of three experts - III. Hellenic J Cardiol  2015; 56(1): 7-9.
 [PMID: 25701966]

[119]
Abdel-Hamid AAM, Firgany AEDL. Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress. J Mol Histol  2015; 46(4-5): 337-45.
 [http://dx.doi.org/10.1007/s10735-015-9625-4] [PMID: 26041576]

[120]
Shin YH, Min JJ, Lee JH, et al. The effect of fluvastatin on cardiac fibrosis and angiotensin-converting enzyme-2 expression in glucose-controlled diabetic rat hearts. Heart Vessels  2017; 32(5): 618-27.
 [http://dx.doi.org/10.1007/s00380-016-0936-5] [PMID: 28013371]

[121]
Ewart MA, Kennedy S. Diabetic cardiovascular disease-AMP-activated protein kinase (AMPK) as a therapeutic target. Cardiovasc Hematol Agents Med Chem  2012; 10(3): 190-211.
 [http://dx.doi.org/10.2174/187152512802651015] [PMID: 22632264]

[122]
Gariballa S, Kosanovic M, Yasin J, Essa A. Oxidative damage and inflammation in obese diabetic Emirati subjects. Nutrients  2014; 6(11): 4872-80.
 [http://dx.doi.org/10.3390/nu6114872] [PMID: 25375631]

[123]
Anichini C, Lotti F, Longini M, Felici C, Proietti F, Buonocore G. Antioxidant strategies in genetic syndromes with high neoplastic risk in infant age. Tumori  2014; 100(6): 590-9.
 [http://dx.doi.org/10.1177/1778.19256] [PMID: 25688491]

[124]
Zozina VI, Covantev S, Goroshko OA, Krasnykh LM, Kukes VG. Coenzyme Q10 in cardiovascular and metabolic diseases: current state of the problem. Curr Cardiol Rev  2018; 14(3): 164-74.
 [http://dx.doi.org/10.2174/1573403X14666180416115428] [PMID: 29663894]

[125]
Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: Results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail  2014; 2(6): 641-9.
 [http://dx.doi.org/10.1016/j.jchf.2014.06.008] [PMID: 25282031]

[126]
Prakoso D, De Blasio MJ, Tate M, et al. Gene therapy targeting cardiac phosphoinositide 3-kinase (p110α) attenuates cardiac remodeling in type 2 diabetes. Am J Physiol Heart Circ Physiol  2020; 318(4): H840-52.
 [http://dx.doi.org/10.1152/ajpheart.00632.2019] [PMID: 32142359]

[127]
Butz H. Circulating noncoding RNAs in pituitary neuroendocrine tumors-two sides of the same coin. Int J Mol Sci  2022; 23(9): 5122.
 [http://dx.doi.org/10.3390/ijms23095122] [PMID: 35563510]

[128]
Gilca GE, Stefanescu G, Badulescu O, Tanase DM, Bararu I, Ciocoiu M. Diabetic cardiomyopathy: Current approach and potential diagnostic and therapeutic targets. J Diabetes Res  2017; 2017: 1-7.
 [http://dx.doi.org/10.1155/2017/1310265] [PMID: 28421204]

[129]
Muñoz-Córdova F, Hernández-Fuentes C, Lopez-Crisosto C, et al. Novel insights into the pathogenesis of diabetic cardiomyopathy and pharmacological strategies. Front Cardiovasc Med  2021; 8: 707336.
 [http://dx.doi.org/10.3389/fcvm.2021.707336] [PMID: 35004869]

[130]
León LE, Rani S, Fernandez M, Larico M, Calligaris SD. Subclinical detection of diabetic cardiomyopathy with microRNAs: Challenges and perspectives. J Diabetes Res  2016; 2016: 1-12.
 [http://dx.doi.org/10.1155/2016/6143129] [PMID: 26770988]

[131]
Zhang Z, Wang S, Zhou S, et al. Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway. J Mol Cell Cardiol  2014; 77: 42-52.
 [http://dx.doi.org/10.1016/j.yjmcc.2014.09.022] [PMID: 25268649]

[132]
Li Z, Xu W, Su Y, et al. Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte. Mol Cell Endocrinol  2019; 495: 110507.
 [http://dx.doi.org/10.1016/j.mce.2019.110507] [PMID: 31315024]

[133]
Yellon DM, Davidson SM. Exosomes. Circ Res  2014; 114(2): 325-32.
 [http://dx.doi.org/10.1161/CIRCRESAHA.113.300636] [PMID: 24436428]

[134]
Dannenberg L, Weske S, Kelm M, Levkau B, Polzin A. Cellular mechanisms and recommended drug-based therapeutic options in diabetic cardiomyopathy. Pharmacol Ther  2021; 228: 107920.
 [http://dx.doi.org/10.1016/j.pharmthera.2021.107920] [PMID: 34171330]

[135]
Hu J, Wang S, Xiong Z, et al. Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy. Biochim Biophys Acta Mol Basis Dis  2018; 1864(11): 3639-49.
 [http://dx.doi.org/10.1016/j.bbadis.2018.08.026] [PMID: 30251683]

[136]
Liu J, Zhang Y, Tian Y, Huang W, Tong N, Fu X. Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications. Theranostics  2022; 12(3): 1342-72.
 [http://dx.doi.org/10.7150/thno.65778] [PMID: 35154494]

[137]
Singla DK. Stem cells and exosomes in cardiac repair. Curr Opin Pharmacol  2016; 27: 19-23.
 [http://dx.doi.org/10.1016/j.coph.2016.01.003] [PMID: 26848944]

[138]
Shepherd DL, Hathaway QA, Nichols CE, et al. Mitochondrial proteome disruption in the diabetic heart through targeted epigenetic regulation at the mitochondrial heat shock protein 70 (mtHsp70) nuclear locus. J Mol Cell Cardiol  2018; 119: 104-15.
 [http://dx.doi.org/10.1016/j.yjmcc.2018.04.016] [PMID: 29733819]

[139]
Hopf AE, Andresen C, Kötter S, et al. Diabetes-induced cardiomyocyte passive stiffening is caused by impaired insulin-dependent titin modification and can be modulated by neuregulin-1. Circ Res  2018; 123(3): 342-55.
 [http://dx.doi.org/10.1161/CIRCRESAHA.117.312166] [PMID: 29760016]

[140]
Rupee S, Rupee K, Singh RB, et al. Diabetes-induced chronic heart failure is due to defects in calcium transporting and regulatory contractile proteins: cellular and molecular evidence. Heart Fail Rev  2022; 2022: 1-8.
 [http://dx.doi.org/10.1007/s10741-022-10271-5] [PMID: 36107271]

[141]
Calligaris SD, Conget P. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy. Biol Res  2013; 46(3): 251-5.
 [http://dx.doi.org/10.4067/S0716-97602013000300005] [PMID: 24346072]

[142]
da Silva JS, Gonçalves RGJ, Vasques JF, et al. Mesenchymal stem cell therapy in diabetic cardiomyopathy. Cells  2022; 11(2): 240.
 [http://dx.doi.org/10.3390/cells11020240] [PMID: 35053356]

[143]
Saraswat N, Wal P, Pal RS, Wal A, Pal Y, Pharmacophore DM. Current review on IRS-1, JNK, NF-KB & m-TOR pathways in insulin resistance. Pharmacophores  2020; 11(1): 1-4.
Rights & Permissions Print Cite
Article Metrics
40
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1573399819666230502110511	Print ISSN 1573-3998
Publisher Name Bentham Science Publisher	Online ISSN 1875-6417
Current Diabetes Reviews

An Insight into the Pathogenesis of Diabetic Cardiomyopathy Along with the Novel Potential Therapeutic Approaches

Abstract

Oxidative and Inflammatory Responses in the Development of Secondary Diabetic Complications

Current Diabetes Reviews

An Insight into the Pathogenesis of Diabetic Cardiomyopathy Along with the Novel Potential Therapeutic Approaches

Abstract

Call for Papers in Thematic Issues

Oxidative and Inflammatory Responses in the Development of Secondary Diabetic Complications

Related Journals

Related Books

Related Articles
