Diabetic cardiomyopathy

Diabetic cardiomyopathy

Presence of myocardial dysfunction in diabetic persons without overt clinical coronary artery disease, valvular heart disease and other conventional cardiovascular risk factors like hypertension and dyslipidemia has been called diabetic cardiomyopathy [1]. As the prevalence of diabetes mellitus is increasing, so is diabetic cardiomyopathy. Initially it manifests as diastolic dysfunction due to myocardial fibrosis and later with systolic dysfunction and finally with clinical heart failure.

Initial description of diabetic cardiomyopathy was in autopsy specimens of four diabetics who heart heart failure symptoms without coronary artery disease or valvular heart disease [2]. It was associated with diabetic glomerulosclerosis. Two years later, a Framingham Heart Study report showed a 5 fold higher incidence of heart failure in diabetic females and 2.4 fold higher incidence in diabetic males [3]. This was after adjustment for other risk factors like age, coronary artery disease and hypertension.

Diabetic cardiomyopathy is related to hyperglycemia, insulin resistance and impaired cardiac insulin metabolic signaling. Associated cellular level abnormalities are mitochondrial dysfunction, endoplasmic reticulum stress and impaired calcium hemostasis. Along with this there is abnormal coronary microcirculation, sympathetic activation and activation of renin-angiotensin-aldosterone axis. These result in oxidative stress, fibrosis and hypertrophy. Early stage of diabetic cardiomyopathy is subclinical, with structural and functional abnormalities. As time passes, it progresses to heart failure with preserved ejection fraction and later into heart failure with reduced ejection fraction [4].

Non-invasive investigations which have been used in the evaluation of diabetic cardiomyopathy are echocardiography, computed tomography and cine magnetic resonance imaging. Biomarkers found elevated in diabetic cardiomyopathy with heart failure were atrial natriuretic peptide, brain natriuretic peptide and O-linked N-acetylglucosamine [1]. Galectin-3 is one of the biomarkers for myocardial fibrosis, found elevated in diabetic cardiomyopathy. Increased release of free fatty acids from adipose tissue and increased capacity of myocyte sarcolemmal free fatty acid transporters also contribute to the development of diabetic cardiomyopathy. Advanced glycation end products of proteins and lipids on exposure to sugars can induce cardiovascular injury through crosslinking of extracellular matrix molecules [5].

Potential treatment strategies that target myocardial fibrosis, inflammation, oxidative stress and insulin resistance have shown promising results in preclinical studies [5]. These need further validation in randomized clinical trials before they can be applied to the specific management of diabetic cardiomyopathy. Till then, only conventional strategies of optimal glycemic control and lipid lowering can be relied on in addition to management of heart failure, in diabetic cardiomyopathy.

References

1. 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. PMID: 29449364; PMCID: PMC5819359.
2. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972 Nov 8;30(6):595-602. doi: 10.1016/0002-9149(72)90595-4. PMID: 4263660.
3. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29-34. doi: 10.1016/0002-9149(74)90089-7. PMID: 4835750.
4. Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol. 2016 Mar;12(3):144-53. doi: 10.1038/nrendo.2015.216. Epub 2015 Dec 18. PMID: 26678809; PMCID: PMC4753054.
5. Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat Rev Cardiol. 2020 Sep;17(9):585-607. doi: 10.1038/s41569-020-0339-2. Epub 2020 Feb 20. PMID: 32080423; PMCID: PMC7849055.