Basic Mechanisms of Diabetic Heart Disease

Diabetes mellitus predisposes affected individuals to a significant spectrum of cardiovascular complications, one of the most debilitating in terms of prognosis is heart failure. Indeed, the increasing global prevalence of diabetes mellitus and an aging population has given rise to an epidemic of diabetes mellitus–induced heart failure. Despite the significant research attention this phenomenon, termed diabetic cardiomyopathy, has received over several decades, understanding of the full spectrum of potential contributing mechanisms, and their relative contribution to this heart failure phenotype in the specific context of diabetes mellitus, has not yet been fully resolved. Key recent preclinical discoveries that comprise the current state-of-the-art understanding of the basic mechanisms of the complex phenotype, that is, the diabetic heart, form the basis of this review. Abnormalities in each of cardiac metabolism, physiological and pathophysiological signaling, and the mitochondrial compartment, in addition to oxidative stress, inflammation, myocardial cell death pathways, and neurohumoral mechanisms, are addressed. Further, the interactions between each of these contributing mechanisms and how they align to the functional, morphological, and structural impairments that characterize the diabetic heart are considered in light of the clinical context: from the disease burden, its current management in the clinic, and where the knowledge gaps remain. The need for continued interrogation of these mechanisms (both known and those yet to be identified) is essential to not only decipher the how and why of diabetes mellitus–induced heart failure but also to facilitate improved inroads into the clinical management of this pervasive clinical challenge.

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Metabolic Complications in Cardiac Aging

Frontiers in Physiology ◽

10.3389/fphys.2021.669497 ◽

2021 ◽

Vol 12 ◽

Author(s):

Thomas Sithara ◽

Konstantinos Drosatos

Keyword(s):

Fatty Acids ◽

Cardiac Function ◽

Ketone Bodies ◽

Atp Synthesis ◽

Cardiac Metabolism ◽

Cardiovascular Complications ◽

Acid Oxidation ◽

Metabolic Complications ◽

Cardiac Aging ◽

Relative Contribution

Aging is a process that can be accompanied by molecular and cellular alterations that compromise cardiac function. Although other metabolic disorders with increased prevalence in aged populations, such as diabetes mellitus, dyslipidemia, and hypertension, are associated with cardiovascular complications; aging-related cardiomyopathy has some unique features. Healthy hearts oxidize fatty acids, glucose, lactate, ketone bodies, and amino acids for producing energy. Under physiological conditions, cardiac mitochondria use fatty acids and carbohydrate mainly to generate ATP, 70% of which is derived from fatty acid oxidation (FAO). However, relative contribution of nutrients in ATP synthesis is altered in the aging heart with glucose oxidation increasing at the expense of FAO. Cardiac aging is also associated with impairment of mitochondrial abundance and function, resulting in accumulation of reactive oxygen species (ROS) and activation of oxidant signaling that eventually leads to further mitochondrial damage and aggravation of cardiac function. This review summarizes the main components of pathophysiology of cardiac aging, which pertain to cardiac metabolism, mitochondrial function, and systemic metabolic changes that affect cardiac function.

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New glucose-lowering drugs in patients with heart failure

Bulgarian Cardiology ◽

10.3897/bgcardio.27.e70144 ◽

2021 ◽

Vol 27 (2) ◽

pp. 60-64

Author(s):

Plamen Gatzov

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Cardiovascular Diseases ◽

Population Aging ◽

Cardiovascular Complications ◽

Glucose Lowering ◽

New Class ◽

Patients With Heart Failure ◽

Causes Of Mortality ◽

Positive Effect

The cardiovascular diseases are one of the main causes of mortality in the countries of Europe and North America. The heart failure (HF) and diabetes mellitus (DM) are widely spread diseases that become more frequent with the population aging in those regions. The algorithm of HF treatment in the last two decades includes several new medications. The SGLT-2 inhibitors (dapagliﬂ ozin, empagliﬂ ozin and canagloﬂ ozin) are new class anti diabetic medications which have positive effect on cardiovascular complications in patients with and without DB. The main trials using those medications in this group of patients and the most probable mechanisms, responsible for their effects, are the topic of this review.

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Abstract 505: Diabetes Mellitus-Induced Metabolic Remodeling is Alleviated by Transgenic Overexpression of Mir-133a in the Heart

Circulation Research ◽

10.1161/res.127.suppl_1.505 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Tyler Kambis ◽

Paras K Mishra

Keyword(s):

Diabetes Mellitus ◽

Cardiac Metabolism ◽

Transport Protein ◽

Diabetic Heart ◽

P Value ◽

Wild Type ◽

Diabetic Mellitus ◽

Metabolic Remodeling ◽

Carnitine Palmitoyltransferase I ◽

Rate Limiting

Diabetic mellitus (DM) cardiomyopathy is a DM-induced metabolic disorder where energy dependence on fatty acid (FA) metabolism causes FA influx overload. While we reported that miR-133a overexpression prevented deleterious lipid accumulation in the diabetic Akita heart, it is unclear whether miR-133a regulates diabetes-induced metabolic remodeling in the DM heart. Thus, we performed deep sequencing on the heart from DM Akita (Ak), cardiac-specific miR-133aTg (Tg), Ak/Tg mice, and sibling wild-type (WT) mice. Ingenuity pathway analysis showed that FAO was the highest activated pathway in the DM heart (p-value=4.59E-11). Therefore, we hypothesized that miR-133a overexpression in the DM heart improves cardiac metabolism by increasing FA clearance via enhancing FA oxidation (FAO). Notably, mitochondrial FA transport protein carnitine palmitoyltransferase I (CPT1) was upregulated (WT: 0.02±0.01, Ak: 0.06±0.02, Ak/Tg: 0.17±0.02, Tg: 0.06±0.01) while changes in the intracellular FA transport protein CD36 were not significant. Interestingly, the rate-limiting enzyme of ketogenesis, the FAO spillover pathway, 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was downregulated (WT: 0.13±0.02, Ak: 0.74±0.13, Ak/Tg: 0.39±0.07, Tg: 0.05±0.01) in Ak/Tg mice. These results support that increased miR-133a in the diabetic heart contributes to improved FAO and FA metabolism in addition to downregulating FA deposition and ketogenesis in the diabetic heart.

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Sodium-Glucose Cotransporter-2 Inhibitors and Cardiovascular Disease: Lessons and the Future

Internal Medicine - Open Journal ◽

10.17140/imoj-4-113 ◽

2020 ◽

Vol 4 (1) ◽

pp. 10-12

Author(s):

Abdulhalim J. A. Kinsara ◽

◽

Atif Al Qubbany ◽

Wail Alkashkar ◽

◽

...

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Communicable Disease ◽

Therapeutic Option ◽

Vascular Complications ◽

Cardiovascular Complications ◽

Diabetic Patients ◽

Reduced Ejection Fraction ◽

Sodium Glucose Cotransporter ◽

Related Hospitalisation

Diabetes mellitus (DM), an epidemic non-communicable disease, is associated with macro- and micro-vascular complications which may result in sudden cardiac death at a young age. Sodium-glucose cotransporter-2 inhibitors (SGLT2-I) emerged as a new therapeutic option for managing DM with cardiovascular complications as well as diabetic patients with multiple risk factors. Three drugs in this class significantly reduced cardiovascular mortality and heart failure events, in both type 2 diabetes mellitus and non-diabetic patients with a reduced ejection fraction, to prevent heart failure-related hospitalisation. Evidence of kidney protection was another major advantage provided in more than one study. We reviewed recent SGLT2-I related literature and discuss the benefits beyond the cardiac system.

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The Burden of Care of Heart Failure in Patients with Diabetes Mellitus: The Peculiarities of Sub-Saharan Africa

10.47363/jcrrr/2020(1)122 ◽

2020 ◽

pp. 1-3

Author(s):

Azeez T A ◽

◽

Oluwasanjo O O ◽

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Cardiovascular Complications ◽

Sub Saharan Africa ◽

Suboptimal Control ◽

Burden Of Care ◽

Heart Failure Patients ◽

The World ◽

Patients With Diabetes ◽

Sub Saharan

Non-communicable diseases are rapidly becoming the commonest cause of mortality in sub-Saharan Africa. Africa has one of the largest prevalence of diabetes mellitus in the world. However, the medical, economic, social and emotional barriers against optimal care of patients with diabetes are very prominent in sub-Saharan Africa. Therefore, poor glycemic control and suboptimal control of other risk factors are not uncommon. These increase the risk of developing cardiovascular complications of diabetes, the endpoint of which is often heart failure. The care for heart failure patients in sub-saharan Africa has been documented to be significantly low when compared with Asia or Southern America. The direct and indirect costs are unbearable and access to care is often compromised. So, when a patient with diabetes develops heart failure in sub-Saharan Africa, the burden is further magnified out of proportion to other developing regions in the world. This review article aims to highlight the peculiarities of the burden of care for heart failure patients with diabetes so that concerted efforts can be directed at addressing the challenges. This will lead to improved care of patients with diabetes and prevent them from developing cardiovascular complications like heart failure or to optimally manage these complications if they arise.

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Atrial fibrillation: a new facet of diabetes mellitus in the XXI century

Diabetes Mellitus ◽

10.14341/2072-0351-6250 ◽

2011 ◽

Vol 14 (1) ◽

pp. 53-60 ◽

Cited By ~ 2

Author(s):

Andrey Alexeevich Aleksandrov ◽

M N Yadrikhinskaya ◽

Svetlana Semenovna Kukharenko

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Atrial Fibrillation ◽

Congestive Heart Failure ◽

Risk Factor ◽

Life Expectancy ◽

Cardiac Rhythm ◽

Cardiovascular Complications ◽

Cardiac Insufficiency

Congestive heart failure, diabetes mellitus, and ciliary arrhythmia are three epidemic cardiovascular conditions threatening the mankind in the XXIcentury. Ciliary arrhythmia is the commonest disturbance of cardiac rhythm characterized by inability of the atrium to maintain coordinated contractions.The importance of ciliary rrhythmia as a problem facing public heath services is underlain by its role as a risk factor of disturbed cerebralcirculation and severe cardiac insufficiency, the two most serious and costly cardiovascular complications influencing life expectancy of the affectedsubjects.

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Hydrogen sulfide: an old gas with new cardioprotective effects

Clinical Science ◽

10.1042/cs20140668 ◽

2014 ◽

Vol 128 (5) ◽

pp. 321-323 ◽

Cited By ~ 4

Author(s):

Vaibhav B. Patel ◽

Brent A. McLean ◽

Xueyi Chen ◽

Gavin Y. Oudit

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Hydrogen Sulfide ◽

Diabetic Cardiomyopathy ◽

Therapeutic Potential ◽

Cardiovascular Complications ◽

Signalling Pathways ◽

Intracellular Signalling Pathways ◽

Signalling Molecule ◽

Cardioprotective Effects

Diabetic cardiovascular complications are reaching epidemic proportions and the risk of HF (heart failure) is increased 2–3-fold by diabetes mellitus. H2S (hydrogen sulfide) is emerging as a new gaseous signalling molecule in the cardiovascular system which possesses multifactorial effects on various intracellular signalling pathways. The proven cardioprotective and vasodilator activities of H2S warrant a detailed investigation into its role in diabetic cardiomyopathy. In the present issue of Clinical Science, Zhou et al. demonstrate an important therapeutic potential of the H2S pathway in diabetic cardiomyopathy.

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