Diabetic Cardiomyopathy: From Mechanism to Management in a Nutshell

Author(s):  
Shahzad Khan ◽  
Syed S. Ahmad ◽  
Mohammad A. Kamal

: Diabetic cardiomyopathy (DCM) is a significant complication of diabetes mellitus characterized by gradual failing heart with detrimental cardiac remodellings such as fibrosis and diastolic and systolic dysfunction, which is not directly attributable to coronary artery disease. Insulin resistance and resulting hyperglycemia is the main trigger involved in the initiation of diabetic cardiomyopathy. There is a constellation of many pathophysiological events such as lipotoxicity, oxidative stress, inflammation, inappropriate activation of the renin-angiotensin-aldosterone system, dysfunctional immune modulation promoting increased rate of cardiac cell injury, apoptosis, and necrosis which ultimately culminates into interstitial fibrosis, cardiac stiffness, diastolic dysfunction initially and later systolic dysfunction too. These events finally lead to clinical heart failure of DCM. Herein, we have briefly discussed the pathophysiology of DCM. We have also briefly mentioned potential therapeutic strategies currently used for DCM.

2021 ◽  
Vol 12 ◽  
Author(s):  
Namrita Kaur ◽  
Yingshu Guan ◽  
Rida Raja ◽  
Andrea Ruiz-Velasco ◽  
Wei Liu

The incidence of heart failure (HF) continues to increase rapidly in patients with diabetes. It is marked by myocardial remodeling, including fibrosis, hypertrophy, and cell death, leading to diastolic dysfunction with or without systolic dysfunction. Diabetic cardiomyopathy (DCM) is a distinct myocardial disease in the absence of coronary artery disease. DCM is partially induced by chronic systemic inflammation, underpinned by a hostile environment due to hyperglycemia, hyperlipidemia, hyperinsulinemia, and insulin resistance. The detrimental role of leukocytes, cytokines, and chemokines is evident in the diabetic heart, yet the precise role of inflammation as a cause or consequence of DCM remains incompletely understood. Here, we provide a concise review of the inflammatory signaling mechanisms contributing to the clinical complications of diabetes-associated HF. Overall, the impact of inflammation on the onset and development of DCM suggests the potential benefits of targeting inflammatory cascades to prevent DCM. This review is tailored to outline the known effects of the current anti-diabetic drugs, anti-inflammatory therapies, and natural compounds on inflammation, which mitigate HF progression in diabetic populations.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Isabelle Pham ◽  
Emmanuel Cosson ◽  
Minh Tuan Nguyen ◽  
Isabela Banu ◽  
Isabelle Genevois ◽  
...  

Aim. Our aim was to assess the prevalence of subclinical diabetic cardiomyopathy, occurring among diabetic patients without hypertension or coronary artery disease (CAD).Methods. 656 asymptomatic patients with type 2 diabetes for 14 ± 8 years (359 men, 59.7 ± 8.7 years old, HbA1c 8.7 ± 2.1%) and at least one cardiovascular risk factor had a cardiac echography at rest, a stress cardiac scintigraphy to screen for silent myocardial ischemia (SMI), and, in case of SMI, a coronary angiography to screen for silent CAD.Results. SMI was diagnosed in 206 patients, and 71 of them had CAD. In the 157 patients without hypertension or CAD, left ventricular hypertrophy (LVH: 24.1%) was the most frequent abnormality, followed by left ventricular dilation (8.6%), hypokinesia (5.3%), and systolic dysfunction (3.8%). SMI was independently associated with hypokinesia (odds ratio 14.7 [2.7–81.7],p<0.01) and systolic dysfunction (OR 114.6 [1.7–7907],p<0.01), while HbA1c (OR 1.9 [1.1–3.2],p<0.05) and body mass index (OR 1.6 [1.1–2.4],p<0.05) were associated with systolic dysfunction. LVH was more prevalent among hypertensive patients and hypokinesia in the patients with CAD.Conclusion. In asymptomatic type 2 diabetic patients, diabetic cardiomyopathy is highly prevalent and is predominantly characterized by LVH. SMI, obesity, and poor glycemic control contribute to structural and functional LV abnormalities.


Author(s):  
Jianxin Deng ◽  
Yunxiu Liao ◽  
Jianpin Liu ◽  
Wenjuan Liu ◽  
Dewen Yan

Diabetic cardiomyopathy (DCM) is characterized by diastolic relaxation abnormalities in its initial stages and by clinical heart failure (HF) without dyslipidemia, hypertension, and coronary artery disease in its last stages. DCM contributes to the high mortality and morbidity rates observed in diabetic populations. Diabetes is a polygenic, heritable, and complex condition that is exacerbated by environmental factors. Recent studies have demonstrated that epigenetics directly or indirectly contribute to pathogenesis. While epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, have been recognized as key players in the pathogenesis of DCM, some of their impacts remain not well understood. Furthering our understanding of the roles played by epigenetics in DCM will provide novel avenues for DCM therapeutics and prevention strategies.


Diabetic cardiomyopathy reflects the presence of structural or functional abnormalities of the myocardium in an individual with diabetes which are not fully explained by other factors known to cause myocardial dysfunction. Diabetes promotes a range of molecular and cellular changes leading to left ventricular concentric hypertrophy, fibrosis, abnormal perfusion, lipid deposition, altered metabolism, diastolic dysfunction, and later progression to systolic dysfunction. Diagnosis of diabetic cardiomyopathy requires identification of such pathological features whilst at the same time excluding other causes of left ventricular dysfunction. In this article, avail- able modalities which can contribute to a diagnosis of diabetic cardiomyopathy are discussed. In most cases a diagnosis of diabetic cardiomyopathy can be reached by echocardiography or cardiac magnetic resonance imaging to detect structural and functional myocardial changes, with computed tomography coronary angiography being employed to exclude obstructive coronary artery disease which could account for left ventricular dysfunction.


2021 ◽  
Vol 11 ◽  
Author(s):  
Amit K. Rai ◽  
Brooke Lee ◽  
Ramesh Gomez ◽  
Deepu Rajendran ◽  
Mahmood Khan ◽  
...  

Diabetic cardiomyopathy (DMCM) is the leading cause of mortality and morbidity among diabetic patients. DMCM is characterized by an increase in oxidative stress with systemic inflammation that leads to cardiac fibrosis, ultimately causing diastolic and systolic dysfunction. Even though DMCM pathophysiology is well studied, the approach to limit this condition is not met with success. This highlights the need for more knowledge of underlying mechanisms and innovative therapies. In this regard, emerging evidence suggests a potential role of non-coding RNAs (ncRNAs), including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) as novel diagnostics, mechanisms, and therapeutics in the context of DMCM. However, our understanding of ncRNAs’ role in diabetic heart disease is still in its infancy. This review provides a comprehensive update on pre-clinical and clinical studies that might develop therapeutic strategies to limit/prevent DMCM.


2021 ◽  
Vol 8 ◽  
Author(s):  
Teresa Salvatore ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
Gaetana Albanese ◽  
Anna Di Martino ◽  
...  

Individuals with diabetes mellitus (DM) disclose a higher incidence and a poorer prognosis of heart failure (HF) than non-diabetic people, even in the absence of other HF risk factors. The adverse impact of diabetes on HF likely reflects an underlying “diabetic cardiomyopathy” (DM–CMP), which may by exacerbated by left ventricular hypertrophy and coronary artery disease (CAD). The pathogenesis of DM-CMP has been a hot topic of research since its first description and is still under active investigation, as a complex interplay among multiple mechanisms may play a role at systemic, myocardial, and cellular/molecular levels. Among these, metabolic abnormalities such as lipotoxicity and glucotoxicity, mitochondrial damage and dysfunction, oxidative stress, abnormal calcium signaling, inflammation, epigenetic factors, and others. These disturbances predispose the diabetic heart to extracellular remodeling and hypertrophy, thus leading to left ventricular diastolic and systolic dysfunction. This Review aims to outline the major pathophysiological changes and the underlying mechanisms leading to myocardial remodeling and cardiac functional derangement in DM-CMP.


Author(s):  
Han-Zhao Zhu ◽  
Li-Yun Zhang ◽  
Meng-En Zhai ◽  
Lin Xia ◽  
Yu Cao ◽  
...  

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.


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