Metabolic syndrome and diabetes are associated with increased risk of cardiac dysfunction independently of underlying coronary artery disease. The underlying pathogenesis is partially understood but accumulating evidence suggests that alterations of cardiac energy metabolism might contribute to the development of contractile dysfunction. Recent findings suggest that myocardial mitochondrial dysfunction may play an important role in the pathogenesis of cardiac contractile dysfunction in type 2 diabetes. This review is focused on evaluating mechanisms for the mitochondrial abnormalities that may be involved in the development and progression of cardiac dysfunction in diabetes.
Coronary Artery Disease ; Diabetic Cardiomyopathies ; Energy Metabolism ; Mitochondria

Cell Transdifferentiation ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Fibroblasts ; Humans ; Myocardium

Apoptosis ; physiology ; Autophagy ; physiology ; Diabetic Cardiomyopathies ; physiopathology ; Humans

Echocardiographic evaluation of left ventricular function permits the demonstration of preclinical diabetic cardiomyopathy. In order to define the relationship between diabetic retinopathy and precence of myocardial dysfunction, M-mode echocardiograms were recorded in three groups of diabetics ; group 1, no retinopathy, group 2, background retinopathy, group 3, proliferative retinopathy, and normal controls without evidence fo coronary heart disease. The resultant traces were digitized, and systolic and diastolic parameters were evaluated. None of parameters fo systolic function was modified. however peak velocity of posterior wall thinning was decreased in group 3(p<0.005), peak velocity of left ventricular demension increase was decreased in all three groups(p<0.005, P<0.001, P<0.001 respectively), duration of rapid thinning of posterior wall increased in group 2 and 3(p<0.001, p<0.001 respectively), and duration of rapid inflow of left ventricle was increased in group 3(p<0.005). These results indicate a diminution of myocardial compliance and relaxation in diabetics with retinopathy. It is concluded that abnormalities of left ventricular diastolic function is present in diabetics when left ventricular systolic function is normal and that more severe abnormalities of left ventricular diastolic function in diabetics with proliferative retinopathy reflect a subclinical diabetic cardiomyopathy due to small vessel disease.
Compliance ; Coronary Disease ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Diabetic Retinopathy ; Echocardiography* ; Heart Ventricles ; Relaxation ; Ventricular Function, Left*

Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.
Brain Diseases ; Diabetes Mellitus ; Diabetic Cardiomyopathies/genetics* ; Diabetic Nephropathies/genetics* ; Humans ; Research Design ; Signal Transduction

Cardiovascular disease is the most common cause of death in patients with diabetes mellitus (DM). In particular, the focus of many studies has been on ischemic heart disease, as it is a eading cause of death in diabetic patients. However, independent of coronary artery disease, DM can also lead to cardiac structural and functional changes, supporting the presence of diabetic cardiomyopathy. The pathologic mechanismin the development of diabetic cardiomyopathy is multifactorial including metabolic disturbance, myocardial fibrosis, microvascular disease, and autonomic dysfunction. Functionally, diabetic patients have a higher prevalence of LV (left ventricle) diastolic dysfunction. Because most diabetic patients with early myocardial disease have a wide spectrum of diastolic dysfunction at rest, assessment of LV functional reserve during exercise is helpful for early identification of myocardial dysfunction. Recent research has demonstrated that LV diastolic functional reserve (DFR) assessed by diastolic stress echocardiography was significantly reduced in patients with DM, compared with a control group, suggesting DFR might be an early indicator of diabetic cardiomyopathy. Glycemic control might be the most important and basic therapeutic strategy for preventing the development of diabetic cardiomyopathy. However, more extensive studies are needed to garner further evidence of preventive and therapeutic strategies of diabetic cardiomyopathy.
Cardiomyopathies ; Cardiovascular Diseases ; Cause of Death ; Coronary Artery Disease ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Diastole ; Echocardiography, Stress ; Fibrosis ; Humans ; Myocardial Ischemia ; Prevalence

BACKGROUND AND OBJECTIVES: Diabetes is associated with a unique form of cardiomyopathy in the absence of atherosclerosis. The mechanisms of diabetic cardiomyopathy have not been defined, but is associated with early left ventricular (LV) diastolic dysfunction following an altered LV contractile performance. However, less attention has been paid to the right ventricular (RV) diastolic function in diabetes. Therefore, the changes in the RV ans LV filling dynamics, in patients with early type 2 diabetes, were investigated. SUBJECTS AND METHODS: The transtricuspid and trans-mitral flows were assessed by transthoracic Doppler echocardiography, at maximal inspiration and expiration, in 48 subjects (mean age: 62+/-9 years, M:F=16:32) with type 2 diabetes (Type 2 DM group) and 34 normal subjects (control group ; mean age:59+/-9 years, M:F=15:19, ranging from 45-75 years of age) with normal LV systolic function and ECG at rest. Subjects with diabetic complication, nephropathy (Cr >1.5 mg/dL), LVH and COPD were excluded. RESULTS: The mitral E/A ratio and DT (deceleration time) showed no significant difference between the type 2 DM and control groups. The LV and RV systolic functions also showed no significant difference between the two groups. However, the type 2 DM group had a lower tricuspid E/A ratio (0.98+/-0.25 vs. 1.17+/-0.21, p<0.001) and a longer tricuspid DT (241+/-65 msec vs. 208+/-51 msec, p=0.016) than the control group. CONCLUSION: The right ventricular diastolic function is frequently abnormal in early type 2 diabetes. This suggests that right ventricular diastolic dysfunction may be an important predictor for the early detection of diabetic cardiomyopathy.
Atherosclerosis ; Cardiomyopathies ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Diastole ; Echocardiography ; Echocardiography, Doppler ; Electrocardiography ; Heart Ventricles ; Humans ; Pulmonary Disease, Chronic Obstructive

Dizziness is a common symptom in patients with diabetes mellitus; it can lead to or may be confused with presyncope or syncope. The causes of these three symptoms include various drugs, metabolic decompensation, cerebrovascular diseases, vestibular diseases, and diabetic autonomic neuropathy. Although cardiac autonomic neuropathy (CAN) in patients with diabetes is associated with increased cardiovascular morbidity and mortality, CAN might exist in a subclinical state before patients develop resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction, and diabetic cardiomyopathy. Thus, it is important to detect CAN in the early phase. This article aimed to review the pathogenesis, manifestations, diagnosis, and treatment of diabetic CAN related to dizziness, presyncope, and syncope.
Cerebrovascular Disorders ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Diabetic Neuropathies* ; Diagnosis ; Dizziness* ; Humans ; Hypotension, Orthostatic ; Mortality ; Syncope* ; Tachycardia ; Vestibular Diseases

Histone methylation is one of the key post-translational modifications that plays a critical role in various heart diseases, including diabetic cardiomyopathy. A great deal of evidence has shown that histone methylation is closely related to hyperglycemia, insulin resistance, lipid and advanced glycation end products deposition, inflammatory and oxidative stress, endoplasmic reticulum stress and cell apoptosis, and these pathological factors play an important role in the pathogenesis of diabetic cardiomyopathy. In order to provide a novel theoretical basis and potential targets for the treatment of diabetic cardiomyopathy from the perspective of epigenetics, this review discussed and elucidated the association between histone methylation and the pathogenesis of diabetic cardiomyopathy in details.
Diabetes Mellitus ; Diabetic Cardiomyopathies/pathology* ; Histones ; Humans ; Methylation ; Oxidative Stress ; Protein Processing, Post-Translational

In the present study, the underlying mechanisms for diabetic functional derangement and insulin effect on diabetic cardiomyopathy were investigated with respect to sarcoplasmic reticulum (SR) Ca2+-ATPase and phospholamban at the transcriptional and translational levels. The maximal Ca2+ uptake and the affinity of Ca2+-ATPase for Ca2+ were decreased in streptozotocin-induced diabetic rat cardiac SR, however, even minimal amount of insulin could reverse both parameters. Levels of both mRNA and protein of phospholamban were significantly increased in diabetic rat hearts, whereas the mRNA and protein levels of SR Ca2+-ATPase were significantly decreased. In case of phospholamban, insulin treatment reverses these parameters to normal levels. Minimal amount of insulin could reverse the protein levels; however, it could not reverse the mRNA level of SR Ca2+-ATPase at all. Thus, the decreased SR Ca2+ uptake appear to be largely attributed to the decreased SR Ca2+-ATPase level, which is further impaired due to the inhibition by the increased level of phospholamban. These results indicate that insulin is involved in the control of intracellular Ca2+ in the cardiomyocyte through multiple target proteins via multiple mechanisms for the decrease in the mRNA for both SR Ca2+-ATPase and phospholamban which are unknown and needs further study.
Animals ; Diabetic Cardiomyopathies ; Heart* ; Insulin* ; Myocytes, Cardiac ; Rats ; RNA, Messenger ; Sarcoplasmic Reticulum*