Diabetic cardiomyopathy

Khavandi, Kaivan; Khavandi, Ali; Asghar, Omar; Greenstein, Adam; Withers, Sarah; Heagerty, AM; Malik, Rayaz A.

doi:10.1016/j.beem.2008.10.016

Cited by 61 publications

(55 citation statements)

References 104 publications

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“…Epidemiological and experimental studies have consistently reported diabetes as a strong risk factor for the development of heart failure even after adjusting for concomitant risks such as coronary artery disease and hypertension. This has resulted in the recognition of a distinct disease process termed as "diabetic cardiomyopathy" [2][3][4]…”

Section: Introductionmentioning

confidence: 99%

Disruption of Nrf2 Synergizes with High Glucose to Cause Heightened Myocardial Oxidative Stress and Severe Cardiomyopathy in Diabetic Mice

2013

J Diabetes Metab

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High glucose-induced oxidative stress is a major contributing mechanism to the development of diabetic cardiomyopathy. Nrf2 is an emerging critical regulator of cellular defense against oxidative damage. The role of Nrf2 in diabetic cardiomyopathy was investigated in vivo. Streptozotocin (STZ) induced diabetes in Nrf2 knockout (KO) mice that rapidly progressed to severe conditions with high mortality within two weeks of injection; whereas, in wild type (WT) mice, diabetes was less severe with no death. Severe myocardial lesions were observed in diabetic KO mice that had high, sublethal levels of blood glucose including: (a) irregular myocardial arrangements, myofibrillar discontinuation, and cell death; (b) reduced electron density, discontinuation of myocardial fibers, and mitochondrial damage; and (c) markedly reduced contractility of the cardiomyocytes to β-agonist stimulation. Parallel to severe cardiomyopathy, the diabetic KO hearts showed: (a) increased apoptosis as revealed by TUNEL and PARP1 cleavage assays; (b) infiltration of granulocytes and macrophages as well as fibrosis indicating robust inflammatory response; and (c) heightened oxidative stress as evidenced by increased levels of 8-hydroxydeoxyquanine, free malondialdehyde, and 3-nitrotyrosine. Increased oxidative stress in the KO hearts was attributed to decrease or loss of the basal and induced expression of Nrf2-dependent cytoprotective genes. Our findings demonstrate that loss of Nrf2 function synergizes with high glucose to cause heightened oxidative stress in the heart leading to severe diabetic cardiomyopathy.

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Section: Introductionmentioning

confidence: 99%

Disruption of Nrf2 Synergizes with High Glucose to Cause Heightened Myocardial Oxidative Stress and Severe Cardiomyopathy in Diabetic Mice

2013

J Diabetes Metab

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“…Increased FFA oxidation promotes mitochondrial uncoupling that may result in reduced myocardial high energy reserves and contractile dysfunction (22,24). FFA's inhibit pyruvate dehydrogenase and leads to accumulation of glycolytic intermediates and ceramides, which enhance apoptosis (2,25). In addition, FFA metabolism for adenosine triphosphate production requires large amounts of oxygen that results in more toxic intermediates (lipotoxicity) which impair myocyte calcium handling, worsening myocardial mechanics (8,15,23,(26)(27)(28)(29).…”

Section: Impaired Free Fatty Acid Metabolismmentioning

confidence: 99%

“…Cardiovascular diseases are responsible from the three quarters of the deaths among this population (2). Although coronary artery disease (CAD) is very common, heart failure (HF) is also a major cause of mortality and morbidity in patients with diabetes mellitus (3).…”

Section: Introductionmentioning

confidence: 99%

Acar¹,

Ural²,

Bildirici³

et al. 2011

Anadolu Kardiyol Derg

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Diabetic individuals are at significantly greater risk of developing heart failure (HF) independent from other risk factors such as coronary artery disease (CAD) and hypertension. Diabetic cardiomyopathy (DCP) is defined as ventricular dysfunction in the absence of hypertension, coronary artery and valvular heart disease, which increases the risk of HF. Due to better understanding of its pathophysiology and clinical importance, DCP is more frequently recognized in daily practice. The most important mechanisms of DCP are hyperglycemia, insulin resistance/hyperinsulinemia, abnormal fatty acid metabolism, increased apoptosis, cardiac autonomic neuropathy and local renin-angiotensin-aldosterone system (RAAS) overactivation. Echocardiography is the most frequently used diagnostic method for the detection of this pathology. Currently, although there is no specific treatment for DCP, strict glycemic and concomitant risk factor controls seems to be the most important target strategy for prevention of the progression and treatment of DCP. In this article, we aim to provide an extensive review on the pathophysiology, diagnosis, management of DCP. (Anadolu Kardiyol Derg 2011; 11: 732-7)

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“…1 Cardiovascular disease is a serious of complication of diabetes and is responsible for 80% of the deaths among diabetics. 2 Although coronary artery disease is very common, heart failure is also a major cause of mortality and morbidity in patients with diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

“…4 The Framingham Heart Study showed that the frequency of heart failure in diabetic men is twice that of nondiabetics, and it is 5 times higher in diabetic women compared to nondiabetic women. 1,5 Diabetic cardiomyopathy (DCMP) was first reported in 1972 by Rubler. 6 It is characterized by the development of diastolic dysfunction at the early stage followed by systolic dysfunction in the absence of coronary artery disease, hypertension, or significant valvular heart disease.…”

mentioning

confidence: 99%

Diagnostic Value of Poor R‐Wave Progression in Electrocardiograms for Diabetic Cardiomyopathy in Type 2 Diabetic Patients

Bildirici

Ural

Acar

et al. 2010

Clinical Cardiology

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Background: Diabetic cardiomyopathy (DCMP) is a common complication of diabetes and is associated with increased mortality. It has been suggested that a poor R-wave progression in a resting electrocardiogram (ECG) could be a sign of cardiomyopathy. Hypothesis: The aim of this study was primarily to analyze the relationship between poor R-wave progression and DCMP, and the effect of poor R-wave progression on cardiac functions in long-term follow-up. Methods: Seventy type 2 normotensive diabetics (33 female, 37 male; mean age, 52.9 ± 10.4 years) were included in the study. Poor R-wave progression in an ECG was defined as an R wave <3 mm in V1-3 derivations. The patients were randomized in 2 groups, which were those without (group I, n = 34) and those with poor R-wave progression (group II, n = 36). All patients underwent conventional and tissue Doppler echocardiography and were followed in an outpatient clinic setting for 4 years. Results: Demographic variables were similar between the 2 groups. In group II, left ventricular (LV) relaxation abnormality was more prevalent, the Tei index was higher, and in tissue Doppler mitral annulus Em velocities were significantly lower and Am velocities were higher than those with normal R-wave progression. At the end of the 4-year follow-up period, LV ejection fraction was decreased in group II, whereas LV mass index and Tei index were significantly increased. Conclusions: LV diastolic dysfunction is more frequently observed in diabetic patients with poor R-wave progression in ECG, which may be an early sign of LV dysfunction and DCMP in diabetics. IntroductionThe prevalence of diabetes is steadily increasing, and the number of diabetic people is expected to reach 300 million globally by 2025. 1 Cardiovascular disease is a serious of complication of diabetes and is responsible for 80% of the deaths among diabetics. 2 Although coronary artery disease is very common, heart failure is also a major cause of mortality and morbidity in patients with diabetes mellitus. 3 Up to 75% of patients with unexplained idiopathic dilated cardiomyopathy were found to be diabetic. 4 The Framingham Heart Study showed that the frequency of heart failure in diabetic men is twice that of nondiabetics, and it is 5 times higher in diabetic women compared to nondiabetic women. 1,5 Diabetic cardiomyopathy (DCMP) was first reported in 1972 by Rubler. 6 It is characterized by the development of diastolic dysfunction at the early stage followed by systolic dysfunction in the absence of coronary artery disease, hypertension, or significant valvular heart disease. 7 -9 In the Strong Heart Study, diabetes was significantly related to higher left ventricular (LV) mass and wall

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Diabetic cardiomyopathy – a distinct disease?

Cited by 61 publications

References 104 publications

Disruption of Nrf2 Synergizes with High Glucose to Cause Heightened Myocardial Oxidative Stress and Severe Cardiomyopathy in Diabetic Mice

Disruption of Nrf2 Synergizes with High Glucose to Cause Heightened Myocardial Oxidative Stress and Severe Cardiomyopathy in Diabetic Mice

Diabetic cardiomyopathy

Diagnostic Value of Poor R‐Wave Progression in Electrocardiograms for Diabetic Cardiomyopathy in Type 2 Diabetic Patients

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