Diabetic cardiomyopathy: diagnostic biomarkers

Main Article Content

V.A. Serhiyenko
A.A. Serhiyenko

Abstract

The review provides a classification of biomarkers of the cardiovascular system diseases, biological markers that have found application in a cardiological clinic, biomarkers of heart failure, modern recommendations on the use of biomarkers for the diagnosis and treatment of acute and chronic heart failure. Special attention is paid to the importance of myocardial pro-hypertrophic biomarkers (atrial natriuretic peptide, brain natriuretic peptide, N-amino terminal fragment of the prohormone B-type natriuretic peptide, cardiotrophin-1); biomarkers of myocardial contractile dysfunction (troponins); pro-steatosis biomarkers of diabetic cardiomyopathy (human heart-type fatty acid binding protein); the value of epicardial adipose tissue; extracellular matrix remodeling markers (matrix metalloproteinases); fibrotic and inflammatory biomarkers (transforming growth factor beta, galectin-3, stimulating growth factor ST2). However, the use of biomarkers to identify left ventricular dysfunction remains a debatable issue. Natriuretic peptides are released in response to the progression of stress-induced cardiomyopathy, which is rare in patients with subclinical dysfunction and left ventricular hypertrophy. Obesity is associated with lower levels of natriuretic peptides, which may impair the sensitivity of the test. However, screening based on natriuretic peptide is effective for detecting moderate diastolic dysfunction. Other potential biomarkers of myocardial dysfunction in diabetes have also been reported, including circulating microribonucleic acids and glucose metabolites (eg, O-GlcNAc) found in circulating erythrocytes. However, a clear consensus has not yet been reached on the clinical role of any of these possible biomarkers.

Article Details

How to Cite
Serhiyenko, V., and A. Serhiyenko. “Diabetic Cardiomyopathy: Diagnostic Biomarkers”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 16, no. 6, Oct. 2020, pp. 442-53, doi:10.22141/2224-0721.16.6.2020.215382.
Section
Literature Review

References

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;2017:1310265. doi:10.1155/2017/1310265.

Ostanko VL, Kalacheva TP, Kalyuzhina EV, et al. Biological markers in risk stratification and progression of cardiovascular disease: present and future. Bull Siberian Med. 2018;17(4):264-80. doi:10.20538/1682-0363-2018-4-264-280. (in Russian).

Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circ Res. 2018 Feb 16;122(4):624-638. doi:10.1161/CIRCRESAHA.117.311586.

Lorenzo-Almorós A, Tuñón J, Orejas M, Cortés M, Egido J, Lorenzo Ó. Diagnostic approaches for diabetic cardiomyopathy. Cardiovasc Diabetol. 2017 Feb 23;16(1):28. doi:10.1186/s12933-017-0506-x.

De Rosa S, Arcidiacono B, Chiefari E, Brunetti A, Indolfi C, Foti DP. Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links. Front Endocrinol (Lausanne). 2018 Jan 17;9:2. doi:10.3389/fendo.2018.00002.

Lee MMY, McMurray JJV, Lorenzo-Almorós A, et al. Diabetic cardiomyopathy. Heart. 2019 Feb;105(4):337-345. doi:10.1136/heartjnl-2016-310342.

Chorna I, Motuziuk O. The Characteristic of the Main Ischemic Damaging Biomarkers of Muscle Tissue. Lesia Ukrainka Eastern European National University Scientific Bulletin Series: Biol Sciences. 2019;387(3):162-72. doi:10.29038/2617-4723-2019-387-162-172. (in Ukrainian).

Biological markers and their use in heart failure. Consensus of Ukrainian Association of Cardiology, Ukrainian Heart Failure Association and Ukrainian Association on Acute Cardiovascular Care. Ukrainian J Cardiol. 2019;26(2):11-22. (in Ukrainian).

Ohkita M, Tawa M, Kitada K, Matsumura Y. Pathophysiological roles of endothelin receptors in cardiovascular diseases. J Pharmacol Sci. 2012;119(4):302-13. doi:10.1254/jphs.12r01cr.

Serhiyenko VA, Serhiyenko AA, Mankovsky BN. Correlation between arterial wall stiffness, N-terminal prohormone of brain natriuretic peptide, functional and structural myocardial abnormalities in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy. Diabetes mellitus. 2013;16(4):72-7. doi:10.14341/DM2013472-77. (in Russian).

D'Alessandro R, Masarone D, Buono A, et al. Natriuretic peptides: molecular biology, pathophysiology and clinical implications for the cardiologist. Future Cardiol. 2013 Jul;9(4):519-34. doi:10.2217/fca.13.32.

Inoue Y, Kawai M, Minai K, et al. The impact of an inverse correlation between plasma B-type natriuretic peptide levels and insulin resistance on the diabetic condition in patients with heart failure. Metabolism. 2016 Mar;65(3):38-47. doi:10.1016/j.metabol.2015.09.019.

Dencker M, Stagmo M, Dorkhan M. Relationship between natriuretic peptides and echocardiography parameters in patients with poorly regulated type 2 diabetes. Vasc Health Risk Manag. 2010 Jun 1;6:373-82. doi:10.2147/vhrm.s9332.

Kiencke S, Handschin R, von Dahlen R, Muser J, et al. Pre-clinical diabetic cardiomyopathy: prevalence, screening, and outcome. Eur J Heart Fail. 2010 Sep;12(9):951-7. doi:10.1093/eurjhf/hfq110.

Nunes S, Soares E, Fernandes J, et al. Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker. Cardiovasc Diabetol. 2013 Mar 7;12:44. doi:10.1186/1475-2840-12-44.

Korkmaz-Icöz S, Lehner A, Li S, et al. Left ventricular pressure-volume measurements and myocardial gene expression profile in type 2 diabetic Goto-Kakizaki rats. Am J Physiol Heart Circ Physiol. 2016 Oct 1;311(4):H958-H971. doi:10.1152/ajpheart.00956.2015.

Ruiz-Hurtado G, Gómez-Hurtado N, Fernández-Velasco M, et al. Cardiotrophin-1 induces sarcoplasmic reticulum Ca(2+) leak and arrhythmogenesis in adult rat ventricular myocytes. Cardiovasc Res. 2012 Oct 1;96(1):81-9. doi:10.1093/cvr/cvs234.

Gamella-Pozuelo L, Fuentes-Calvo I, Gómez-Marcos MA, et al. Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk. Medicine (Baltimore). 2015 Jul;94(30):e1218. doi:10.1097/MD.0000000000001218.

García-Cenador MB, Lopez-Novoa JM, Díez J, García-Criado FJ. Effects and mechanism of organ protection by cardiotrophin-1. Curr Med Chem. 2013;20(2):246-56. doi:10.2174/092986713804806702.

Moreno-Aliaga MJ, Romero-Lozano MA, Castaño D, Prieto J, Bustos M. Role of cardiotrophin-1 in obesity and insulin resistance. Adipocyte. 2012 Apr 1;1(2):112-115. doi:10.4161/adip.19696.

Gamella-Pozuelo L, Fuentes-Calvo I, Gómez-Marcos MA, et al. Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk. Medicine (Baltimore). 2015 Jul;94(30):e1218. doi:10.1097/MD.0000000000001218.

Hung HC, Lu FH, Ou HY, et al. Increased cardiotrophin-1 in subjects with impaired glucose tolerance and newly diagnosed diabetes. Int J Cardiol. 2013 Nov 5;169(3):e33-4. doi:10.1016/j.ijcard.2013.08.112.

Russell NE, Higgins MF, Amaruso M, Foley M, McAuliffe FM. Troponin T and pro-B-type natriuretic Peptide in fetuses of type 1 diabetic mothers. Diabetes Care. 2009 Nov;32(11):2050-5. doi:10.2337/dc09-0552.

Nyman K, Granér M, Pentikäinen MO, et al. Cardiac steatosis and left ventricular function in men with metabolic syndrome. J Cardiovasc Magn Reson. 2013 Nov 14;15(1):103. doi:10.1186/1532-429X-15-103.

Hoffmann U, Espeter F, Weiß C, et al. Ischemic biomarker heart-type fatty acid binding protein (hFABP) in acute heart failure - diagnostic and prognostic insights compared to NT-proBNP and troponin I. BMC Cardiovasc Disord. 2015 Jun 14;15:50. doi:10.1186/s12872-015-0026-0.

García-Rúa V, Otero MF, Lear PV, et al. Increased expression of fatty-acid and calcium metabolism genes in failing human heart. PLoS One. 2012;7(6):e37505. doi:10.1371/journal.pone.0037505.

Fosshaug LE, Dahl CP, Risnes I, et al. Altered Levels of Fatty Acids and Inflammatory and Metabolic Mediators in Epicardial Adipose Tissue in Patients With Systolic Heart Failure. J Card Fail. 2015 Nov;21(11):916-23. doi:10.1016/j.cardfail.2015.07.014.

Ziyrek M, Kahraman S, Ozdemir E, Dogan A. Metformin monotherapy significantly decreases epicardial adipose tissue thickness in newly diagnosed type 2 diabetes patients. Rev Port Cardiol. 2019 Jun;38(6):419-423. doi:10.1016/j.repc.2018.08.010.

Wang TD, Lee WJ, Shih FY, et al. Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity. Atherosclerosis. 2010 Nov;213(1):279-87. doi:10.1016/j.atherosclerosis.2010.07.055.

Greulich S, de Wiza DH, Preilowski S, et al. Secretory products of guinea pig epicardial fat induce insulin resistance and impair primary adult rat cardiomyocyte function. J Cell Mol Med. 2011 Nov;15(11):2399-410. doi:10.1111/j.1582-4934.2010.01232.x.

Blumensatt M, Wronkowitz N, Wiza C, et al. Adipocyte-derived factors impair insulin signaling in differentiated human vascular smooth muscle cells via the upregulation of miR-143. Biochim Biophys Acta. 2014 Feb;1842(2):275-83. doi:10.1016/j.bbadis.2013.12.001.

Chen WJ, Greulich S, van der Meer RW, et al. Activin A is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes. Cardiovasc Diabetol. 2013 Oct 17;12:150. doi:10.1186/1475-2840-12-150.

Mahabadi AA, Berg MH, Lehmann N, et al. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol. 2013 Apr 2;61(13):1388-95. doi:10.1016/j.jacc.2012.11.062.

Cavalcante JL, Tamarappoo BK, Hachamovitch R, et al. Association of epicardial fat, hypertension, subclinical coronary artery disease, and metabolic syndrome with left ventricular diastolic dysfunction. Am J Cardiol. 2012 Dec 15;110(12):1793-8. doi:10.1016/j.amjcard.2012.07.045.

Abazid RM, Smettei OA, Kattea MO, et al. Relation Between Epicardial Fat and Subclinical Atherosclerosis in Asymptomatic Individuals. J Thorac Imaging. 2017 Nov;32(6):378-382. doi:10.1097/RTI.0000000000000296.

Wu FZ, Chou KJ, Huang YL, Wu MT. The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies. BMC Cardiovasc Disord. 2014 May 4;14:62. doi:10.1186/1471-2261-14-62.

Nerlekar N, Muthalaly RG, Wong N, et al. Association of Volumetric Epicardial Adipose Tissue Quantification and Cardiac Structure and Function. J Am Heart Assoc. 2018 Dec 4;7(23):e009975. doi:10.1161/JAHA.118.009975.

Vrselja Z, Šram M, Andrijevic D, et al. Transcardial gradient of adiponectin, interleukin-6 and tumor necrosis factor-α in overweight coronary artery disease patients. Cytokine. 2015 Dec;76(2):321-327. doi:10.1016/j.cyto.2015.09.009.

Fitzgibbons TP, Czech MP. Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations. J Am Heart Assoc. 2014 Mar 4;3(2):e000582. doi:10.1161/JAHA.113.000582.

Shimabukuro M, Hirata Y, Tabata M, et al. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2013 May;33(5):1077-84. doi:10.1161/ATVBAHA.112.300829.

Psaltis PJ, Talman AH, Munnur K, et al. Relationship between epicardial fat and quantitative coronary artery plaque progression: insights from computer tomography coronary angiography. Int J Cardiovasc Imaging. 2016 Feb;32(2):317-328. doi:10.1007/s10554-015-0762-3.

Koval SM, Yushko KO, Snihurska IO, et al. Relations of angiotensin-(1-7) with hemodynamic and cardiac structural and functional parameters in patients with hypertension and type 2 diabetes. Arterial Hypertension. 2019;23(3):183-189. doi:10.5603/AH.a2019.0012.

Sokolova LK, Belchina YuV, Pushkarev VV, et al. The blood level of endothelin-1 in diabetic patients depending on the characterisric of the disease. Mìžnarodnij endokrinologìčnij žurnal. 2020;16(3):35-45. doi:10.22141/2224-0721.16.3.2020.205267.

Ban CR, Twigg SM, Franjic B, et al. Serum MMP-7 is increased in diabetic renal disease and diabetic diastolic dysfunction. Diabetes Res Clin Pract. 2010 Mar;87(3):335-41. doi:10.1016/j.diabres.2010.01.004.

Zaslavskaya EL, Morozov AN, Ionin VA, et al. The Role Of Transforming Growth Factor Beta-1 And Galectin-3 In Formation Of The Left Atrium Fibrosis In Patients With Paroxysmal Atrial Fibrillation And Metabolic Syndrome. Russ J Cardiol. 2018;2:60-66. doi:10.15829/1560-4071-2018-2-60-66. (in Russian).

Tan SM, Zhang Y, Wang B, et al. FT23, an orally active antifibrotic compound, attenuates structural and functional abnormalities in an experimental model of diabetic cardiomyopathy. Clin Exp Pharmacol Physiol. 2012 Aug;39(8):650-6. doi:10.1111/j.1440-1681.2012.05726.x.

Biernacka A, Cavalera M, Wang J, et al. Smad3 Signaling Promotes Fibrosis While Preserving Cardiac and Aortic Geometry in Obese Diabetic Mice. Circ Heart Fail. 2015 Jul;8(4):788-98. doi:10.1161/CIRCHEARTFAILURE.114.001963.

Hutchinson KR, Lord CK, West TA, Stewart JA Jr. Cardiac fibroblast-dependent extracellular matrix accumulation is associated with diastolic stiffness in type 2 diabetes. PLoS One. 2013 Aug 21;8(8):e72080. doi:10.1371/journal.pone.0072080.

Shaver A, Nichols A, Thompson E, et al. Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population. Int J Med Sci. 2016 Feb 5;13(3):161-8. doi:10.7150/ijms.14141.

Russo I, Frangogiannis NG. Diabetes-associated cardiac fibrosis: Cellular effectors, molecular mechanisms and therapeutic opportunities. J Mol Cell Cardiol. 2016 Jan;90:84-93. doi:10.1016/j.yjmcc.2015.12.011.

Musimkhan MK, Berkinbaev SF, Shanazarov NA, Karabaeva RZ, Kisikova SD. Review of diagnostic methods for predicting the course of heart failure in patients with coronary artery disease. Modern problems of science and education. 2018;2:1-13. doi:10.17513/spno.27450. (in Russian).

Menini S, Iacobini C, Blasetti Fantauzzi C, Pesce CM, Pugliese G. Role of Galectin-3 in Obesity and Impaired Glucose Homeostasis. Oxid Med Cell Longev. 2016;2016:9618092. doi:10.1155/2016/9618092.

Flores-Ramírez R, Azpiri-López JR, González-González JG, et al. Global longitudinal strain as a biomarker in diabetic cardiomyopathy. A comparative study with Gal-3 in patients with preserved ejection fraction. Arch Cardiol Mex. 2017 Oct-Dec;87(4):278-285. doi:10.1016/j.acmx.2016.06.002.

He J, Yu Z. The role of Galectin-3 in cardiac remodeling. Cardiol Plus. 2016;1(3):28-36. doi:10.4103/2470-7511.248355.

Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017 Aug 8;70(6):776-803. doi:10.1016/j.jacc.2017.04.025.

Pascual-Figal DA, Lax A, Perez-Martinez MT, del Carmen Asensio-Lopez M, Sanchez-Mas J; GREAT Network. Clinical relevance of sST2 in cardiac diseases. Clin Chem Lab Med. 2016 Jan;54(1):29-35. doi:10.1515/cclm-2015-0074.

Rodrigues PG, Leite-Moreira AF, Falcão-Pires I. Myocardial reverse remodeling: how far can we rewind? Am J Physiol Heart Circ Physiol. 2016 Jun 1;310(11):H1402-22. doi:10.1152/ajpheart.00696.2015.

Alonso N, Lupón J, Barallat J, et al. Impact of diabetes on the predictive value of heart failure biomarkers. Cardiovasc Diabetol. 2016 Nov 3;15(1):151. doi:10.1186/s12933-016-0470-x.

Huynh K, Bernardo BC, McMullen JR, Ritchie RH. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther. 2014 Jun;142(3):375-415. doi:10.1016/j.pharmthera.2014.01.003.

Guo R, Nair S. Role of microRNA in diabetic cardiomyopathy: From mechanism to intervention. Biochim Biophys Acta Mol Basis Dis. 2017 Aug;1863(8):2070-2077. doi:10.1016/j.bbadis.2017.03.013.