Manifestation Of Diabetic Cardiomyopathy Research Articles

Prevalence of Cardiomyopathy in Patients with Type 1 Diabetes Mellitus.

Background: Diabetic cardiac muscle disease or diabetic cardiomyopathy (DbCM) comprises a set of myocardial lesions that are not associated with coronary atherosclerosis or high blood pressure. It is characterized by fibrosis and hypertrophy, which ultimately results in heart failure. Diastolic dysfunction (DD) has been shown to be the first manifestation of diabetic cardiomyopathy. Currently, there are few studies on the prevalence of diabetic cardiomyopathy in adult patients diagnosed with type 1 diabetes mellitus (T1D). Methods: The study included 75 adult participants who underwent an echocardiogram. Data on their comorbidities were collected from their medical records and biochemical parameters were analyzed in blood and urine samples. Results: We found that the prevalence of DbCM in our T1D population was more than one-third (34%), which exceeded the prevalence reported in studies with adolescents and that reported in the population without diabetes. Also, we found that the probability of developing DD after 20 years of T1D diagnosis was 78%. Conclusions: Recommendations need to be issued in relation to diabetic cardiomyopathy to carry out secondary prevention in adult patients with T1D. More multicenter studies, which include a larger population, from different regions of the world need to be performed.

INFLUENCE OF N-ACETYLCYSTEINE AND LOSARTAN ON THE EARLY ELECTROCARDIOGRAPHIC CHANGES IN RATS WITH STREPTOZOTOCIN TYPE 1 DIABETES MELLITUS

Aim. To determine the early electrocardiographic onset of experimental diabetic cardiomyopathy (DC) in rats and evaluate its changes under the exposure to N- acetylcysteine and losartan.
 Materials and methods. Type 1 diabetes mellitus (DM1) in rats was induced by using streptozotocin (STZ) in a dose of 50mg/kg. Experimental animals were divided into 5 groups: control (intact animals which were administered placebo -saline as vehicle); DM1 (group of model animals with STZ DM1); NAC (diabetic rats which were administered N-acetylcysteine in a dose of 1,5g/kg per os); LOS (diabetic rats which were administered losartan in a dose of 20mg/kg per os); NAC+LOS (diabetic rats which were administered combination of N- acetylcysteine and losartan). ECG was registered in II standard lead.
 Results. On the 1-st week of STZ DM1 we didn't observe significant changes in rats. It was determined that due to stable hyperglycemia starting from 2-d experimental week occur the early ECG changes, which were characterized by lowering of heart rate, alteration of P wave, prolongation of QTc, decreasing of T wave, which pointed at impairment of ventricular repolarization. More significant differences were observed on 4-5 week of experimental DM1, to specified challenges were added bradycardia progression, deterioration of AV conduction and ventricular depolarization. All of the pharmacological schemes have indicated positive response on heart rhythm, ventricular contractive activity and hypertrophy challenge. More evident influence after 5 weeks of STZ DM1 was obtained for NAC, which possible due to its antioxidant action, decrease hyperglycemia-induced manifestation of DC.
 Conclusion. Administration of NAC and LOS on the early stages of DC manifestation prevent disturbance of heart rhythm, ventricular depolarization and repolarization as well as inhibiting hypertrophy development, minimizing risk for sudden cardiac death.

Abstract 12183: Strain Dispersion is an Early Subclinical Manifestation of Diabetic Cardiomyopathy Assessed by 3D Echocardiography

Introduction: The risk of heart failure is increased in patients with type 2 diabetes mellitus (type 2 DM) independently of risk factors such as coronary artery disease. The causes of diabetic cardiomyopathy are multifactorial and not fully elucidated. 3D echocardiography deformation imaging provides a non-invasive assessment of the structure and function of the left ventricle (LV) and has been shown to improve risk evaluation in patients with congestive cardiac failure (CCF). Objective: The aim of this study was to assess the earliest subclinical manifestations of diabetic cardiomyopathy using deformation imaging. Method: 20 patients (mean age 58.6±1.8) with early-onset, uncomplicated type 2 DM, 20 healthy volunteers (mean age 53.3±2.8) and 10 patients with advanced CCF (NYHA class III+IV) (mean age 69.2±3.0) were studied. Strain dispersion was assessed by calculating the standard deviation of time to peak longitudinal strain across 16 segments of the LV. Results: Diabetic patients were matched with the controls for age and gender. Strain dispersion was increased in patients with type 2 DM when compared to healthy controls (p= 0.001) and global longitudinal strain was decreased (p=0.001). Strain dispersion in type 2 DM and CCF cohorts yielded similar values and were not significantly different (46.5±6.4 vs 52.2±7.9, respectively p=0.3). Conclusion: Strain dispersion is increased in uncomplicated type 2 DM patients with a short duration of disease. 3D echocardiographic deformation imaging is a sensitive non-invasive tool that could be helpful in the assessment of subclinical cardiac involvement in patients with type 2 DM.

Myocardial steatosis, impaired energetics and reduced circumferential strain are early manifestations of diabetic cardiomyopathy and precede structural changes

Background Patients with diabetes mellitus (DM) of longer duration have an increased incidence of heart failure, independent of hypertension and coronary disease, as shown in large population based studies. Mechanisms of diabetic cardiomyopathy are multifactorial and not fully elucidated. Cardiovascular magnetic resonance (CMR) and magnetic resonance spectrocopy (MRS) provide a noninvasive assessment of the functional, structural and metabolic status of the heart. Here we assessed whether subclinical functional, structural and metabolic alterations can be detected using MRI in a patient cohort of early-onset, stable and uncomplicated type 2 DM. Objective The aim of this study was to assess the earliest manifestations of diabetic cardiomyopathy using multiparametric CMR and MRS in a cohort of uncomplicated type 2 DM patients with a short duration of disease. Methods

Cardiac Dysfunction in Rats with Dietary-Induced Insulin Resistance Associated with Pharmacologically-induced Dyslipidemia

Metabolic disorders such as insulin resistance (IR) and dyslipidemia (DL) might contribute to the induction of diabetic cardiomyopathy (DCM). However, few relevant animal models are currently available for studying the time-course of DCM and evaluating experimental therapeutics. The present study proposes a rodent model of dietary-induced IR combined or not with DL in order to investigate the impact of chronic IR and DL on in vivo myocardial function. Male rats were fed a western-type diet (65% fat; 15% fructose; WD). DL was induced by combining the western diet with i.p. injections of a nonionic surface-active agent (P-407; 0.2 mg/kg, 3 times/wk; P-407). A chow diet was used as control. At 11 and 14 weeks, cardiac function was assessed by echocardiography. Fasting blood glucose increased in WD group while plasma lipids markedly accumulated in P-407 treated rats. Echocardiographic data showed no significant difference in cardiac geometry under basal conditions. Diastolic dysfunction was evidenced at 14 weeks by a significant decrease in E/A ratio in the P-407 group. Moreover, fractional shortening was significantly depressed under dobutamine stress in WD group at 14 weeks whereas systolic dysfunction appeared as early as 11 weeks and worsened at 14 weeks in P-407 animals. Finally, myocardial TNF-alpha tissue content increased in P-407 group. In conclusion, DL exacerbated cardiac lipotoxicity and functional complications associated with IR. This experimental model of combined IR and DL closely mimics the main clinical manifestations of DCM and might therefore constitute a useful tool for the evaluation of pharmacological treatments.

Abstract 315: Coenzyme Q 10 Protects Against Diabetes-Induced Diastolic Dysfunction and Adverse Cardiac Remodeling in a Mouse Model of Type 1 Diabetes

Diastolic dysfunction is often the earliest manifestation of diabetic cardiomyopathy, usually accompanied by adverse cardiac remodeling and increased oxidative stress. We tested the hypothesis that administration of Coenzyme Q 10 (CoQ) attenuates type 1 diabetes-induced left ventricular (LV) dysfunction and remodeling. Further, we aimed to compare the efficacy of CoQ to the ACEI, ramipril. Male 6-week old mice received either streptozotocin (STZ, 55mg/kg/day for 5 days) to induce diabetes, or citrate buffer. After 4 weeks, mice were treated with either CoQ dissolved in olive oil (10mg/kg/day), olive oil alone, ramipril (3mg/kg/day) or left untreated for 8 weeks (n=11-14/group). Diabetic mice had increased blood glucose levels compared with non-diabetic controls. Superoxide (O 2 - ) production was enhanced in untreated diabetic mice, and attenuated with CoQ treatment. Diastolic function was impaired in diabetic mice, on Doppler echocardiography (E/A ratio, deceleration time DT) and catheterization (LV end diastolic pressure EDP and LV-dP/dt). Administration of CoQ ameliorated diastolic dysfunction on E/A ratio, DT and LVEDP in diabetic mice, with a similar trend on LV-dP/dt. Although DT and LVEDP were improved with ramipril treatment, E/A ratio was not. Diabetic mice also exhibited cardiomyocyte hypertrophy (H&E staining), cardiac fibrosis (Sirius red staining) and increased apoptosis. Both CoQ and ramipril reduced these markers of adverse LV remodeling. In conclusion, these data suggest that both CoQ and ramipril can attenuate diabetic cardiomyopathy. Addition of CoQ to standard care may offer improved treatment of diastolic dysfunction in diabetic patients.

131 Left ventricular systolic function deterioration during dobutamine stress echocardiography as an early manifestation of diabetic cardiomyopathy and reversal by optimized therapeutic approach

131 Left ventricular systolic function deterioration during dobutamine stress echocardiography as an early manifestation of diabetic cardiomyopathy and reversal by optimized therapeutic approach

Left ventricular systolic function deterioration during dobutamine stress echocardiography as an early manifestation of diabetic cardiomyopathy and reversal by optimized therapeutic approach

Diabetes mellitus has been associated with changes in the structure and function of the myocardium manifesting in the early stages of the disease as subtle systolic and diastolic dysfunction; the role of dobutamine stress echocardiography (DSE) in this setting remains unclear. We sought to evaluate the prevalence of dobutamine-induced systolic dysfunction amongst diabetic patients with normal at rest left ventricular ejection fraction and no coronary artery disease and to investigate whether an optimized therapeutic approach can reverse these abnormalities. 1,363 patients with DM referred to our echocardiography laboratory for DSE between January 2008 and June 2010 were prospectively investigated. Patients with normal left ventricular ejection fraction (LVEF) at rest and significant deterioration during peak dobutamine infusion (defined as a ≥10% decrease) in the absence of coronary artery disease or vasospasm were enrolled. They received on top of their usual treatment 5 mg perindopril and had their glycemic control intensified. At 60 days, all of them were controlled for clinical status and underwent a control DSE. 18 patients were included, there were 9 males and 9 females, mean age was 66.1 ± 10.2 years. All the patients had type II DM with a mean duration of 12.7 ± 6.6 years. They all had normal at rest echocardiographic findings with no wall motion abnormalities; mean LVEF was 62 ± 6%. At peak dobutamine, LVEF significantly deteriorated in all the patients with a mean 15 ± 5% decrease compared to baseline. After therapeutic optimization, Glycated haemoglobin improved from 8.53 ± 2.05% to 6.8 ± 0.6% (δ HbA1C = 1.73%, P = 0.001), mean LVEF at peak dobutamine infusion evolved from 47.17 ± 4.2% pre-optimization to 58 ± 4.8% at control (10.83% improvement; P < 0.001). In patients with DM and normal at rest LVEF, Dobutamine infusion during DSE can induce a significant deterioration in LVEF in the absence of coronary artery disease or vasospasm. This specific condition could be largely reversed through an optimized therapy based on a tighter metabolic control and a more stringent renin-angiotensin-aldosterone system inhibition.

Link between diabetes and diastolic dysfunction and the diagnostic role of echocardiography

Diabetes mellitus, a disease that has been reaching epidemic proportions, is an important risk factor to the development of cardiovascular complication. The left ventricular diastolic dysfunction represents the earliest pre-clinical manifestation of diabetic cardiomyopathy, preceding systolic dysfunction and being able to evolve to symptomatic heart failure. In early stages, these changes appear reversible with tight metabolic control, but as pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients. Doppler echocardiography provides reliable data in the stages of diastolic function, as well as for systolic function. Combination of pulsed tissue Doppler study of mitral annulus with transmitral inflow may be clinically valuable for obtaining information about left ventricular filling pressure and unmasking Doppler inflow pseudonormal pattern, a hinge point for the progression toward advanced heart failure. Subsequently we give an overview about diabetes and its complications, their clinical relevance and the role of echocardiography in detection of diastolic heart failure in diabetes.

Abstract 3212: Dietary-Induced Insulin Resistance Associated with Dyslipidemia Induces Progressive Cardiac Dysfunction in Rats as Evidenced by Echocardiography

Background: A major complication of diabetes is the development of cardiac dysfunction in absence of vascular disease. Metabolic disorders such as insulin resistance (IR) and dyslipidemia (DL) might contribute to the induction of diabetic cardiomyopathy (DCM). However, few relevant animal models are currently available for studying the time-course of DCM and evaluating experimental therapeutics. We developed a rodent model of dietary-induced IR combined or not with DL in order to investigate the impact of chronic IR and DL on in vivo myocardial function. Methods &amp; Results: Male Sprague-Dawley rats were fed a western-type diet (65% fat; 15% fructose; WD: n=12). DL was induced by combining the western diet with i.p . injections of a nonionic surface-active agent (P-407; 0.2 mg/kg, 3 times/wk; WD-P407 n=9). A chow diet was used as control (Chow: n=9). At 6, 11 and 14 wks, cardiac function was assessed by echocardiography. After 6 wks, plasma insulin was significantly increased in both WD and WD-P407 groups ( P&lt; 0.05 vs. Chow). Fasting blood glucose increased in WD group while plasma lipids markedly accumulated in WD-P407-treated rats ( P&lt; 0.05 and P&lt; 0.01 vs. Chow, respectively). Pulse-wave Doppler indicated impaired diastolic function at 14 wks (E/A wave ratio: WD-P407: 1.42±0.06 vs. Chow: 1.65±0.11). M-mode imaging showed no significant differences in cardiac function and geometry under basal conditions. However, fractional shortening (FS) was significantly depressed under dobutamine stress in WD group at 14 wks (FS in % of baseline: 151±9% vs 196±7%; P&lt; 0.05) whereas systolic dysfunction appeared as early as 11 wks and worsened at 14 wks in WD-P407 animals ( P&lt; 0.05 and P&lt; 0.01 vs. Chow, respectively). Finally, compared to Chow, myocardial lipid tissue content and pro-inflammatory cytokine TNF-α were significantly higher in WD and WD-P407 groups, the cardiac lipid accumulation being more pronounced in the later. Conclusions: DL exacerbated cardiac lipotoxicity and functional complications associated with IR. This experimental model of combined IR and DL closely mimics the main clinical manifestations of DCM and might therefore constitute a useful tool for the evaluation of pharmacological treatments.

Detection of Left Ventriculer Diastolic Dysfunction (LVDD) in Asymptomatic, Normotensive, ETT Negative Newly Detected Type-2 Diabetic Patients by Doppler Echocardiography

Left ventricular diastolic dysfunction (LVDD) is the early manifestation of diabetic Cardiomyopathy, which is most often asymptomatic in early stage.

IMPACT OF DIASTOLIC DYSFUNCTION ON MAXIMAL TREADMILL PERFORMANCE IN TYPE 2 DIABETIC SUBJECTS WITHOUT CLINICAL HEART DISEASE

1828 Left ventricular diastolic dysfunction (LVDD) may be the first manifestation of diabetic cardiomyopathy. This could explain impaired peak exercise performance attained in subjects with type 2 diabetes in exercise training studies. Men with type 2 diabetes were separated into 2 groups (n=16/group) on the basis of LVDD 1) absence or 2) presence. They were matched for age and were without evidence of hypertension, gross proteinuria, coronary artery disease, congestive heart failure and thyroid disease. Subjects did not use any cardiovascular medications and were sedentary during the preceding year. Diastolic function was evaluated with echocardiographic standard criteria. Resting systolic function was normal in all subjects. Each performed a symptom-limited modified Bruce protocol treadmill exercise test. Maximal treadmill performance was higher in subjects with normal diastolic function compared to subjects with LVDD (11.6 ± 0.5 vs 10.0 ± 0.6 METs respectively, means ± SE, p<0.05). There were no significant differences in maximal heart rate, and maximal systolic or diastolic blood pressure. In conclusion, this study demonstrated that LVDD influences maximal treadmill performance. This suggests that in this well-characterized cohort of men with type 2 diabetes and without detectable heart disease, impaired left ventricular diastolic dysfunction could explain lower maximal performance found in this high-risk population.