Diabetes and Heart Failure: What’s the Connection
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Diabetes and Heart Failure: What’s the Connection

Ruihan Ma 1*
1 King’s College London
*Corresponding author: Maruihan66@gmail.com
Published on 24 September 2025
Journal Cover
TNS Vol.138
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-381-9
ISBN (Online): 978-1-80590-382-6
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Abstract

Diabetes mellitus and heart failure are two common chronic conditions that frequently coexist, producing outcomes worse than either disease alone. This paper investigates how diabetes directly impairs the myocardium, leading to a distinct syndrome often termed diabetic cardiomyopathy, and examines the reciprocal influence of both disorders. Evidence from clinical and experimental studies highlights altered myocardial metabolism, oxidative stress, glycation pathways, calcium dysregulation, mitochondrial injury, inflammatory signaling, and autonomic imbalance as contributors to structural and functional decline. Analysis of pharmacological data shows that sodium–glucose cotransporter-2 inhibitors consistently improve outcomes across heart failure phenotypes, while glucagon-like peptide-1 receptor agonists offer benefits mainly in obesity-related HFpEF. By contrast, several older glucose-lowering drugs may worsen congestion or remain neutral in prognosis. The review concludes that diabetes and heart failure form a complex, self-reinforcing network, and that targeted treatment strategies grounded in mechanistic understanding are critical for advancing patient care and clinical outcomes.

Keywords:

Diabetic cardiomyopathy, Reactive oxygen species, SGLT2 inhibitors, GLP-1 receptor agonists

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Ma,R. (2025). Diabetes and Heart Failure: What’s the Connection. Theoretical and Natural Science,138,13-18.

References

[1]. Dunlay SM, Givertz MM, Aguilar D, et al. (2019) Type 2 Diabetes Mellitus and Heart Failure: A Scientific Statement From the American Heart Association and the Heart Failure Society of America: This statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. 140(7): e294-e324. doi: 10.1161/CIR.0000000000000691

[2]. From A.M, Scott C.G, Chen H.H. (2010) The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol. 55(4): 300-305. doi: 10.1016/j.jacc.2009.12.003

[3]. Rubler S., Dlugash J., Yuceoglu Y.Z., Kumral T., Branwood A.W., Grishman A. (1972) New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 30(6): 595-602.

[4]. Jia G., Hill M.A., Sowers J.R. (2018) Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circ Res. 122(4): 624-638.

[5]. Ritchie R.H., Abel E.D. (2020) Basic Mechanisms of Diabetic Heart Disease. Circ Res. 126(11): 1501-1525. doi: 10.1161/CIRCRESAHA.120.315913

[6]. Boudina S., Abel E.D. (2007) Diabetic cardiomyopathy revisited. Circulation. 115(25): 3213-3223. doi: 10.1161/CIRCULATIONAHA.106.679597

[7]. Yang P., Feng J., Peng Q., Liu X., Fan Z. (2019) Advanced Glycation End Products: Potential Mechanism and Therapeutic Target in Cardiovascular Complications under Diabetes. Oxid Med Cell Longev. 2019: 9570616. doi: 10.1155/2019/9570616

[8]. Anderson M.E., Brown J.H., Bers D.M. (2011) CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol. 51(4): 468-473. doi: 10.1016/j.yjmcc.2011.01.012

[9]. Bugger H., Abel E.D. (2014) Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 57(4): 660-671. doi: 10.1007/s00125-014-3171-6

[10]. Ramesh P., Yeo J.L., Brady E.M., McCann G.P. (2022) Role of inflammation in diabetic cardiomyopathy. Ther Adv Endocrinol Metab. 13: 20420188221083530.

[11]. Ridker P.M., Everett B.M., Thuren T., et al. (2017) Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 377(12): 1119-1131.

[12]. Vinik A.I., Maser R.E., Mitchell B.D., Freeman R. (2003) Diabetic autonomic neuropathy. Diabetes Care. 26(5): 1553-1579. doi: 10.2337/diacare.26.5.1553

[13]. McMurray J.J.V., Solomon S.D., Inzucchi S.E., et al. (2019) Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 381(21): 1995-2008.

[14]. Anker S.D., Butler J., Filippatos G., et al. (2021) Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021; 385(16): 1451-1461.

[15]. Heerspink H.J.L., Stefánsson B.V., Correa-Rotter R., et al. (2020) Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 383(15): 1436-1446. doi: 10.1056/NEJMoa2024816

[16]. Saucedo-Orozco H., Voorrips S.N., Yurista S.R., de Boer R.A., Westenbrink B.D. (2022) SGLT2 Inhibitors and Ketone Metabolism in Heart Failure. J Lipid Atheroscler. 11(1): 1-19.

[17]. Baartscheer A., Schumacher C.A., Wüst R.C., et al. (2017) Empagliflozin decreases myocardial cytoplasmic Na+through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia. 60(3): 568-573. doi: 10.1007/s00125-016-4134-x

[18]. Marso S.P., Daniels G.H., Brown-Frandsen K., et al. (2016) Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 375(4): 311-322. doi: 10.1056/NEJMoa1603827

[19]. Marso S.P., Bain S.C., Consoli A., et al. (2016) Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 375(19): 1834-1844. doi: 10.1056/NEJMoa1607141

[20]. Holman R.R., Bethel M.A., Mentz R.J., et al. (2017) Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 377(13): 1228-1239.

[21]. Kosiborod M.N., Abildstrøm S.Z., Borlaug B.A., et al. (2023) Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 389(12): 1069-1084.

[22]. Kosiborod M.N., Petrie M.C., Borlaug B.A., et al. (2024) Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. 390(15): 1394-1407.

[23]. Dormandy J.A., Charbonnel B., Eckland D.J., et al. (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 366(9493): 1279-1289. doi: 10.1016/S0140-6736(05)67528-9

[24]. Scirica B.M., Bhatt D.L., Braunwald E., et al. (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 369(14): 1317-1326.

[25]. Eurich D.T., Majumdar S.R., McAlister F.A., Tsuyuki R.T., Johnson J.A. (2005) Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 28(10): 2345-2351. doi: 10.2337/diacare.28.10.2345

[26]. Shah K.S., Xu H., Matsouaka R.A., et al. (2017) Heart Failure With Preserved, Borderline, and Reduced Ejection Fraction: 5-Year Outcomes. J Am Coll Cardiol. 70(20): 2476-2486.

[27]. Lam C.S.P., Arnott C., Beale A.L., et al. (2019) Sex differences in heart failure. Eur Heart J. 40(47): 3859-3868c. doi: 10.1093/eurheartj/ehz835

[28]. Goldman A., Fishman B., Twig G., et al. (2023) The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study. Cardiovasc Diabetol. Jan 24, 22(1): 16.

References

[1]. Dunlay SM, Givertz MM, Aguilar D, et al. (2019) Type 2 Diabetes Mellitus and Heart Failure: A Scientific Statement From the American Heart Association and the Heart Failure Society of America: This statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. 140(7): e294-e324. doi: 10.1161/CIR.0000000000000691

[2]. From A.M, Scott C.G, Chen H.H. (2010) The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol. 55(4): 300-305. doi: 10.1016/j.jacc.2009.12.003

[3]. Rubler S., Dlugash J., Yuceoglu Y.Z., Kumral T., Branwood A.W., Grishman A. (1972) New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 30(6): 595-602.

[4]. Jia G., Hill M.A., Sowers J.R. (2018) Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circ Res. 122(4): 624-638.

[5]. Ritchie R.H., Abel E.D. (2020) Basic Mechanisms of Diabetic Heart Disease. Circ Res. 126(11): 1501-1525. doi: 10.1161/CIRCRESAHA.120.315913

[6]. Boudina S., Abel E.D. (2007) Diabetic cardiomyopathy revisited. Circulation. 115(25): 3213-3223. doi: 10.1161/CIRCULATIONAHA.106.679597

[7]. Yang P., Feng J., Peng Q., Liu X., Fan Z. (2019) Advanced Glycation End Products: Potential Mechanism and Therapeutic Target in Cardiovascular Complications under Diabetes. Oxid Med Cell Longev. 2019: 9570616. doi: 10.1155/2019/9570616

[8]. Anderson M.E., Brown J.H., Bers D.M. (2011) CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol. 51(4): 468-473. doi: 10.1016/j.yjmcc.2011.01.012

[9]. Bugger H., Abel E.D. (2014) Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 57(4): 660-671. doi: 10.1007/s00125-014-3171-6

[10]. Ramesh P., Yeo J.L., Brady E.M., McCann G.P. (2022) Role of inflammation in diabetic cardiomyopathy. Ther Adv Endocrinol Metab. 13: 20420188221083530.

[11]. Ridker P.M., Everett B.M., Thuren T., et al. (2017) Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 377(12): 1119-1131.

[12]. Vinik A.I., Maser R.E., Mitchell B.D., Freeman R. (2003) Diabetic autonomic neuropathy. Diabetes Care. 26(5): 1553-1579. doi: 10.2337/diacare.26.5.1553

[13]. McMurray J.J.V., Solomon S.D., Inzucchi S.E., et al. (2019) Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 381(21): 1995-2008.

[14]. Anker S.D., Butler J., Filippatos G., et al. (2021) Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021; 385(16): 1451-1461.

[15]. Heerspink H.J.L., Stefánsson B.V., Correa-Rotter R., et al. (2020) Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 383(15): 1436-1446. doi: 10.1056/NEJMoa2024816

[16]. Saucedo-Orozco H., Voorrips S.N., Yurista S.R., de Boer R.A., Westenbrink B.D. (2022) SGLT2 Inhibitors and Ketone Metabolism in Heart Failure. J Lipid Atheroscler. 11(1): 1-19.

[17]. Baartscheer A., Schumacher C.A., Wüst R.C., et al. (2017) Empagliflozin decreases myocardial cytoplasmic Na+through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia. 60(3): 568-573. doi: 10.1007/s00125-016-4134-x

[18]. Marso S.P., Daniels G.H., Brown-Frandsen K., et al. (2016) Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 375(4): 311-322. doi: 10.1056/NEJMoa1603827

[19]. Marso S.P., Bain S.C., Consoli A., et al. (2016) Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 375(19): 1834-1844. doi: 10.1056/NEJMoa1607141

[20]. Holman R.R., Bethel M.A., Mentz R.J., et al. (2017) Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 377(13): 1228-1239.

[21]. Kosiborod M.N., Abildstrøm S.Z., Borlaug B.A., et al. (2023) Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 389(12): 1069-1084.

[22]. Kosiborod M.N., Petrie M.C., Borlaug B.A., et al. (2024) Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. 390(15): 1394-1407.

[23]. Dormandy J.A., Charbonnel B., Eckland D.J., et al. (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 366(9493): 1279-1289. doi: 10.1016/S0140-6736(05)67528-9

[24]. Scirica B.M., Bhatt D.L., Braunwald E., et al. (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 369(14): 1317-1326.

[25]. Eurich D.T., Majumdar S.R., McAlister F.A., Tsuyuki R.T., Johnson J.A. (2005) Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 28(10): 2345-2351. doi: 10.2337/diacare.28.10.2345

[26]. Shah K.S., Xu H., Matsouaka R.A., et al. (2017) Heart Failure With Preserved, Borderline, and Reduced Ejection Fraction: 5-Year Outcomes. J Am Coll Cardiol. 70(20): 2476-2486.

[27]. Lam C.S.P., Arnott C., Beale A.L., et al. (2019) Sex differences in heart failure. Eur Heart J. 40(47): 3859-3868c. doi: 10.1093/eurheartj/ehz835

[28]. Goldman A., Fishman B., Twig G., et al. (2023) The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study. Cardiovasc Diabetol. Jan 24, 22(1): 16.

Cite this article

Ma,R. (2025). Diabetes and Heart Failure: What’s the Connection. Theoretical and Natural Science,138,13-18.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: Computational Modelling and Simulation for Biology and Medicine

ISBN: 978-1-80590-381-9(Print) / 978-1-80590-382-6(Online)
Editor: Alan Wang, Roman Bauer
Conference website: https://2025.icbiomed.org/london.html
Conference date: 19 October 2025
Series: Theoretical and Natural Science
Volume number: Vol.138
ISSN: 2753-8818(Print) / 2753-8826(Online)

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