Generic placeholder image

Current Hypertension Reviews


ISSN (Print): 1573-4021
ISSN (Online): 1875-6506

Review Article

Heart Failure and Diabetes: Perspective of a Dangerous Association

Author(s): Liliana E. Favaloro*, Roxana D. Ratto and Carla Musso

Volume 17, Issue 2, 2021

Published on: 06 April, 2021

Page: [85 - 93] Pages: 9

DOI: 10.2174/1573402117666210406111927

Price: $65


The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that, added to other risk factors, favors the development of coronary heart disease. The mechanism by which, in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathy has been less studied.

Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine.

This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.

Keywords: Heart failure (HF), T2D Mellitus, cardiovascular disease (CVD), heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), sodium-glucose cotransport-2 inhibitors (SGLT2 inhibitors).

« Previous
Graphical Abstract
Sociedad Argentina de Cardiología. Consenso De Insuficiencia Cardíaca Crónica. Rev Argent Cardiol 2016; 84(3): 1-50.
International Diabetes Federation (IDF). IDF Diabetes Atlas - 2019. International Diabetes Federation 2019.
Faden G, Faganello G, De Feo S, et al. The increasing detection of asymptomatic left ventricular dysfunction in patients with Type 2 diabetes mellitus without overt cardiac disease: data from the SHORTWAVE study. Diabetes Res Clin Pract 2013; 101(3): 309-16.
[] [PMID: 23886659]
Boonman-de Winter LJM, Rutten FH, Cramer MJM, et al. High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with Type 2 diabetes. Diabetologia 2012; 55(8): 2154-62.
[] [PMID: 22618812]
Sherrill JW. Cardiovascular disease in diabetes mellitus: An analysis of four hundred and twenty-five cases. Cal West Med 1933; 38(2): 73-8.
[PMID: 18742430]
Kannel WB, McGee DL. Diabetes and cardiovascular disease. The framingham study. JAMA 1979; 241(19): 2035-8.
[] [PMID: 430798]
Senthil AN, Ravishankar G, Ravi MS, et al. Pattern of coronary artery disease in symptomatic Type 2 diabetic subjects in the contemporary era and the difference from past studies. Indian Heart J 2014; 66: S46.
Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in Type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol 2018; 17(1): 83.
[] [PMID: 29884191]
Rawshani A, Rawshani A, Franzén S, et al. Mortality and cardiovascular disease in Type 1 and Type 2 diabetes. N Engl J Med 2017; 376(15): 1407-18.
[] [PMID: 28402770]
Cheng YJ, Imperatore G, Geiss LS, et al. Trends and disparities in cardiovascular mortality among U.S. Adults with and without self-reported diabetes, 1988–2015. Diabetes Care 2018; 41(11): 2306-15.
[] [PMID: 30131397]
Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: A cohort study in 1.9 million people. Lancet Diabetes Endocrinol 2015; 3(2): 105-13.
[] [PMID: 25466521]
Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001; 103(22): 2668-73.
[] [PMID: 11390335]
King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): Clinical and therapeutic implications for Type 2 diabetes. Br J Clin Pharmacol 1999; 48: 643-8.
Alexander CM. Is heart failure still the frequent, forgotten, and often fatal complication of diabetes? J Am Coll Cardiol 2020; 75: 1263-5.
Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: An update of mechanisms contributing to this clinical entity. Circ Res 2018; 122(4): 624-38.
[] [PMID: 29449364]
McHugh K, DeVore AD, Wu J, et al. Heart failure with preserved ejection fraction and diabetes: JACC state-of-the-art review. J Am Coll Cardiol 2019; 73(5): 602-11.
[] [PMID: 30732715]
Bell DSH. Heart failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 2003; 26(8): 2433-41.
[] [PMID: 12882875]
Seferović PM, Petrie MC, Filippatos GS, et al. Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2018; 20(5): 853-72.
[] [PMID: 29520964]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in Type 2 diabetes. N Engl J Med 2015; 373(22): 2117-28.
[] [PMID: 26378978]
Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol 2018; 17(1): 6.
[] [PMID: 29301516]
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21): 1995-2008.
[] [PMID: 31535829]
Lundbaek K. Diabetic angiopathy: A specific vascular disease. Lancet 1954; 266(6808): 377-9.
[] [PMID: 13131862]
Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972; 30(6): 595-602.
[] [PMID: 4263660]
Gollmer J, Zirlik A, Bugger H. Mitochondrial mechanisms in diabetic cardiomyopathy. Diabetes Metab J 2020; 44: 33-5.
Filardi T, Ghinassi B, Di Baldassarre A, Tanzilli G, Morano S, Lenzi A. Cardiomyopathy associated with diabetes: The central role of the cardiomyocyte. Int J Mol Sci 2019; 20(13): 3299.
[] [PMID: 31284374]
Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia 2014; 57(4): 660-71.
[] [PMID: 24477973]
Zhou Q, Lv D, Chen P, et al. MicroRNAs in diabetic cardiomyopathy and clinical perspectives. Front Genet 2014; 5: 185.
[] [PMID: 25009554]
Huynh K, Bernardo BC, McMullen JR, Ritchie RH. Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther 2014; 142: 375-415.
Masuo K, Rakugi H, Ogihara T, Esler MD, Lambert GW. Cardiovascular and renal complications of Type 2 diabetes in obesity: Role of sympathetic nerve activity and insulin resistance. Curr Diabetes Rev 2010; 6(2): 58-67.
[] [PMID: 20034369]
Shen JZ, Young MJ. Corticosteroids, heart failure, and hypertension: A role for immune cells? Endocrinology 2012; 153(12): 5692-700.
[] [PMID: 23125312]
de Simone G, Devereux RB, Chinali M, et al. Diabetes and incident heart failure in hypertensive and normotensive participants of the Strong Heart Study. J Hypertens 2010; 28(2): 353-60.
[] [PMID: 19844184]
Redfield MM. Heart failure with preserved ejection fraction. N Engl J Med 2016; 375(19): 1868-77.
De Keulenaer GW, Brutsaert DL. Systolic and diastolic heart failure are overlapping phenotypes within the heart failure spectrum. Circulation 2011; 123(18): 1996-2004.
[] [PMID: 21555722]
Seferović PM, Paulus WJ. Clinical diabetic cardiomyopathy: A two-faced disease with restrictive and dilated phenotypes. Eur Heart J 2015; 36(27): 1718-27.
[] [PMID: 25888006]
Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75: 422-34.
Scheen AJ. Effect of SGLT2 inhibitors on the sympathetic nervous system and blood pressure. Curr Cardiol Rep 2019; 21(8): 70.
Okada K, Hoshide S, Kato M, Kanegae H, Ishibashi S, Kario K. Safety and efficacy of empagliflozin in elderly Japanese patients with Type 2 diabetes mellitus: A post hoc analysis of data from the SACRA study. J Clin Hypertens (Greenwich) 2021; 23(4): 860-9.
[PMID: 33326172]
Kario K, Okada K, Kato M, et al. Twenty-four-hour blood pressure-lowering effect of a sodium-glucose cotransporter 2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension: Results from the randomized, placebo-controlled SACRA Study. Circulation 2019; 139(18): 2089-97.
Kario K, Okada K, Murata M, et al. Effects of luseogliflozin on arterial properties in patients with Type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study. J Clin Hypertens (Greenwich) 2020; 22(9): 1585-93.
[] [PMID: 32810338]
Kario K, Hoshide S, Okawara Y, et al. Effect of canagliflozin on nocturnal home blood pressure in Japanese patients with Type 2 diabetes mellitus: The SHIFT-J study. J Clin Hypertens (Greenwich) 2018; 20(10): 1527-35.
[] [PMID: 30246286]
Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol 2019; 73(15): 1931-44.
[] [PMID: 30999996]
Maruyama T, Takashima H, Oguma H, et al. Canagliflozin improves erythropoiesis in diabetes patients with anemia of chronic kidney disease. Diabetes Technol Ther 2019; 21(12): 713-20.
[] [PMID: 31385724]
Uthman L, Baartscheer A, Bleijlevens B, et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: Inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia 2018; 61(3): 722-6.
[] [PMID: 29197997]
Oh CM, Cho S, Jang JY, et al. Cardioprotective potential of an SGLT2 inhibitor against doxorubicin-induced heart failure. Korean Circ J 2019; 49(12): 1183-95.
[] [PMID: 31456369]
Zhang N, Feng B, Ma X, Sun K, Xu G, Zhou Y. Dapagliflozin improves left ventricular remodeling and aorta sympathetic tone in a pig model of heart failure with preserved ejection fraction. Cardiovasc Diabetol 2019; 18(1): 107.
[] [PMID: 31429767]
Packer M. SGLT2 inhibitors produce cardiorenal benefits by promoting adaptive cellular reprogramming to induce a state of fasting mimicry: A paradigm shift in understanding their mechanism of action. Diabetes Care 2020; 43(3): 508-11.
[] [PMID: 32079684]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in Type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[] [PMID: 28605608]
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in Type 2 diabetes. N Engl J Med 2019; 380(4): 347-57.
[] [PMID: 30415602]
Kato ET, Silverman MG, Mosenzon O, et al. Effect of dapagliflozin on heart failure and mortality in Type 2 diabetes mellitus. Circulation 2019; 139(22): 2528-36.
DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol 2017; 13: 11-26.
Fitchett DH. Empagliflozin and cardio-renal outcomes in patients with Type 2 diabetes and cardiovascular disease - implications for clinical practice. Eur Endocrinol 2018; 14(2): 40-9.
[] [PMID: 30349593]
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in Type 2 diabetes and nephropathy. N Engl J Med 2019; 380(24): 2295-306.
[] [PMID: 30990260]
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020; 383(15): 1436-46.
[] [PMID: 32970396]
Klajda MD, Scott CG, Rodeheffer RJ, Chen HH. Diabetes mellitus is an independent predictor for the development of heart failure: A population study. Mayo Clin Proc 2020; 95(1): 124-33.
[] [PMID: 31902407]
Packer M. Potentiation of insulin signaling contributes to heart failure in Type 2 diabetes: A hypothesis supported by both mechanistic studies and clinical trials. JACC Basic Transl Sci 2018; 3(3): 415-9.
[] [PMID: 30062227]
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in Type 2 diabetes. N Engl J Med 2016; 375(4): 323-34.
[] [PMID: 27299675]
Kario K, Ferdinand KC, O’Keefe JH. Control of 24-hour blood pressure with SGLT2 inhibitors to prevent cardiovascular disease. Prog Cardiovasc Dis 2020; 63: 249-62.
Kario K, Weber M, Ferrannini E. Nocturnal hypertension in diabetes: Potential target of sodium/glucose cotransporter 2 (SGLT2) inhibition. J Clin Hypertens 2018; 20: 424-8.
Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes 2021. Diabetes Care 2021; 44(Suppl. 1): S111-24.
[PMID: 33298420]
Kario K, Harada N, Hoshide S. Randomized, “head-to-head” studies comparing different SGLT2 inhibitors are definitely needed. J Clin Hypertens 2020; 22: 2391-2.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy