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

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Karina Huynh ◽  
Helen Kiriazis ◽  
Xiao-Jun Du ◽  
Jane E Love ◽  
Karin Jandeleit-Dahm ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diastolic Dysfunction ◽  
Olive Oil ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Coenzyme Q ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Diabetic Mice

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.

Abstract 16595: Insulin Replacement Attenuates Autonomic Impairment but Did Not Prevent Early Diastolic Dysfunction in a Model of Type 1 Diabetes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sarah C Freitas ◽  
Paulo M Dourado ◽  
Iris C Sanches ◽  
Jacqueline F machi ◽  
Maria C Irigoyen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diastolic Dysfunction ◽  
Wall Thickness ◽  
Baroreflex Sensitivity ◽  
Insulin Treatment ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Type I ◽  
Insulin Replacement

Introduction: Insulin replacement is the most widely used therapy for treatment of patients with Type 1 Diabetes Mellitus. However, despite a restricted glycemic control, diabetic patients are prone to chronic complications, such as cardiovascular disease. The mechanisms underlying this increased risk are not well understood. Hypothesis: The insulin replacement therapy can prevent the cardiac and autonomic dysfunctions in a model of type 1 diabetes. Methods: 18 male Wistar rats (230-260g) were divided into 3 groups (n=6/group): control (C), diabetic (D, streptozotocin 50 mg/kg) and diabetic treated daily with insulin subcutaneously (DTI). At 30 days, cardiac function was assessed by echocardiogram and after the rats were cannulated and arterial pressure (AP) was recorded. Results: The diabetic groups showed hyperglycemia (>350mg/dl) at the beginning of the protocol. Insulin therapy normalized the glycemia (DTI: 94±28 and C: 126±8 vs. D: 533±67 mg/dl). There was a reduction in the posterior wall thickness of the left ventricle at diastole (PWD) and in the relative wall thickness (RWT) in D group and these changes were not observed in DTI group (PWD- C: 0.122±0.008 and DTI: 0.126±0.004 vs. D: 0.086±0.006 cm and RWT- C: 0.42±0.021 and DTI: 0.4±0.013 vs. D: 0.35±0.014). Left ventricular mass was reduced in D group (D: 0.393±0.0510 vs. C: 0.581±0,054 and DTI: 0.586±0.049). The systolic function was not different (shortening fraction) between the groups. Regarding diastolic function, the isovolumetric relaxation time was not different between the groups, but there was a decrease in E/A wave ratio in the group of diabetic rats, which was not reversed by insulin treatment (D: 1.53±0.104 and DTI: 1.69±0.178 vs. C: 2.45±0.380). The baroreflex sensitivity was impaired in D group in relation to C and DTI groups (D: 1.05±0.110 vs. C: 1.39±0.100 and DTI: 1.36±0.09 bpm/mmHg). The insulin treatment normalized mean AP (DTI: 118±3.34 and C: 110±3.28 vs. D: 99±5.48 mmHg). Conclusions: Treatment with insulin despite normalize blood glucose, baroreflex sensitivity, hemodynamics and cardiac morphometry, was not able to attenuate diastolic dysfunction, suggesting a remaining cardiovascular risk even after insulin replacement in this model of experimental diabetes type I.

Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients

2001 ◽  
Vol 281 (5) ◽  
pp. E1029-E1036 ◽  
Author(s):  
Raymond R. Russell ◽  
Deborah Chyun ◽  
Steven Song ◽  
Robert S. Sherwin ◽  
William V. Tamborlane ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Radionuclide Angiography ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
Plasma Catecholamine ◽  
Ventricular Ejection Fraction ◽  
Type 1 Diabetic Patients

Insulin-induced hypoglycemia occurs commonly in intensively treated patients with type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these patients are not known. We studied left ventricular systolic [left ventricular ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by equilibrium radionuclide angiography during insulin infusion (12 pmol · kg−1 · min−1) under either hypoglycemic (∼2.8 mmol/l) or euglycemic (∼5 mmol/l) conditions in intensively treated patients with type 1 diabetes and healthy nondiabetic subjects ( n = 9 for each). During hypoglycemic hyperinsulinemia, there were significant increases in LVEF (ΔLVEF = 11 ± 2%) and PFR [ΔPFR = 0.88 ± 0.18 end diastolic volume (EDV)/s] in diabetic subjects as well as in the nondiabetic group (ΔLVEF = 13 ± 2%; ΔPFR = 0.79 ± 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but occurred earlier in the nondiabetic group. A blunted increase in plasma catecholamine, cortisol, and glucagon concentrations occurred in response to hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF also increased in both the diabetic (ΔLVEF = 7 ± 1%) and nondiabetic (ΔLVEF = 4 ± 2%) groups, but PFR increased only in the diabetic group. In the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia, only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac output in the hypoglycemic study ( P < 0.05 for each). Thus intensively treated type 1 diabetic patients demonstrate delayed augmentation of ventricular function during moderate insulin-induced hypoglycemia. Although diabetic subjects have a more pronounced cardiac response to hyperinsulinemia per se than nondiabetic subjects, their response to hypoglycemia is blunted.

Abstract 26: Fibroblast Growth Factor 21 Prevents Diabetic Cardiomyopathy by Attenuating Cardiac Lipotoxicity via Erk1/2-dependent Signaling Pathway in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yi Tan ◽  
Chi Zhang ◽  
Xiaoqing Yan ◽  
Zhifeng Huang ◽  
Junlian Gu ◽  
...  
Keyword(s):  
Cell Death ◽  
Type 1 Diabetes ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Cell ◽  
Diabetic Mice ◽  
Ampk Signaling

The role of FGF21 plays in the development and progression of diabetic cardiomyopathy (DCM) has not been addressed. Here we demonstrated that type 1 diabetes decreased FGF21 levels in the blood, but up-regulated cardiac fgf21 expression about 40 fold at 2 months and 3-1.5 fold at 4 and 6 months after diabetes, which indicated a cardiac specific FGF21 adaptive up-regulation. To define the critical role of FGF21 in DCM, type 1 diabetes was induced in FGF21 knock out (FGF21KO) mice. At 1, 2 and 4 months after diabetes onset, no significant differences between FGF21KO and wild type (WT) diabetic mice in blood glucose and triglyceride levels were observed. But FGF21KO diabetic mice showed earlier and more severe cardiac dysfunction, remodeling and oxidative stress, as well as greater increase in cardiac lipid accumulation than WT diabetic mice. Mechanistically, FGF21 reduced palmitate-induced cardiac cell death, which was accompanied by up-regulation of cardiac Erk1/2, p38 MAPK and AMPK phosphorylation. Inhibition of each kinase with its inhibitor and/ or siRNA revealed that FGF21 prevents palmitate-induced cardiac cell death via up-regulating the Erk1/2-dependent p38 MAPK/AMPK signaling pathway. In vivo administration of FGF21, but not FGF21 plus ERK1/2 inhibitor, to diabetic mice significantly prevented cardiac cell death and reduced inactivation of Erk1/2, p38 MAPK and AMPK, and prevented cardiac remodeling and dysfunction at late-stage. Our results demonstrate that cardiac FGF21 decompensation may contribute to the development of DCM and FGF21 may be a therapeutic target for the treatment of diabetic cardiac damage via activation of Erk1/2-P38 MAPK-AMPK signaling.

scholarly journals Assessment of Subclinical Left Ventricular Systolic and Diastolic Dysfunction in Patients with Type 1 DM with and without Good Metabolic Control

2021 ◽  
pp. 51-59
Author(s):  
Hesham Ali Elbahgy ◽  
Mohamed Khalfallah ◽  
Randa Mohamed Abdel-Meged ◽  
Mai M. Abd Elmoneim Salama
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Metabolic Control ◽  
Speckle Tracking ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Group A ◽  
Group B

Background: Diabetic patients with normal left ventricular ejection fraction (LVEF)are frequently associated with diastolic dysfunction. However, LVEF is known not to be a sensitive marker for the detection of subclinical LV systolic dysfunction. This study aimed to assess left ventricular systolic and diastolic function in asymptomatic type 1 diabetic patients by conventional, tissue Doppler and two-dimensional speckle tracking echocardiography to assess subclinical left ventricular systolic and diastolic dysfunction. Methods: Case-control study was conducted at 150 patients aged 15-35 y were subdivided into three equal groups: Group A: with type 1 diabetes mellitus (T1DM) with good metabolic control (Hb A1C <7.0), Group B: T1DM with poor metabolic control (Hb A1C>7.0), and Group C: Control group: included 50 normal healthy subjects. Results: Tissue Doppler, diastolic function and strain parameters, AP4C LS, AP2C LS, AP3C LS, and GLS were significantly impaired among the three groups. AP4C LS, AP2C LS, AP3C LS, and GLS were significantly lower in group B than group A and group C and was significantly lower in group A than group C, A velocity was significantly impaired among the three groups. A velocity was significantly higher in group B than group A and group C and was insignificantly impaired in group A than group C. Conclusion: Conventional echocardiography parameters were insignificantly different between the study groups. 2D speckle tracking and tissue Doppler echocardiography showed that subclinical left ventricular systolic function may be affected even before affection of diastolic function. Longer duration and poor glycemic control of diabetes significantly affect GLS.

scholarly journals Left Ventricular Diastolic Dysfunction in Type 2 Diabetes—Progress and Perspectives

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 121 ◽  
Author(s):  
Elena-Daniela Grigorescu ◽  
Cristina-Mihaela Lacatusu ◽  
Mariana Floria ◽  
Bogdan-Mircea Mihai ◽  
Ioana Cretu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Cardiovascular Events ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Screening Programs ◽  
Ventricular Diastolic Dysfunction

In-depth understanding of early cardiovascular manifestations in diabetes is high on international research and prevention agendas given that cardiovascular events are the leading cause of death for diabetic patients. Our aim was to review recent developments in the echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) as a telltale pre-clinical disturbance preceding diabetic cardiomyopathy. We analyzed papers in which patients had been comprehensively assessed echocardiographically according to the latest LVDD guidelines (2016), and those affording comparisons with previous, widely used recommendations (2009). We found that the updated algorithm for LVDD is more effective in predicting adverse cardiovascular events in patients with established LVDD, and less specific in grading other patients (labelled “indeterminate”). This may prove instrumental for recruiting “indeterminate” LVDD cases among patients with type 2 diabetes mellitus (T2DM) in future screening programs. As an interesting consideration, the elevated values of the index E/e’ can point to early diastolic impairment, foretelling diabetic cardiomyopathy. Identifying subclinical signs early makes clinical sense, but the complex nature of T2DM calls for further research. Specifically, longitudinal studies on rigorously selected cohorts of diabetic patients are needed to better understand and predict the subtle, slow onset of cardiac manifestations with T2DM as a complicating backdrop.

scholarly journals Histological evidence of chitosan-encapsulated curcumin suppresses heart and kidney damages on streptozotocin-induced type-1 diabetes in mice model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sabri Sudirman ◽  
Ching-Shu Lai ◽  
Yi-Ling Yan ◽  
Hung-I Yeh ◽  
Zwe-Ling Kong
Keyword(s):  
Type 1 Diabetes ◽  
Total Cholesterol Level ◽  
Human Life ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Mice Model ◽  
High Blood Glucose

Abstract High blood glucose in diabetic patients often causes cardiovascular diseases (CVDs) that threats to human life. Curcumin (Cur) is known as an antioxidant agent, possesses anti-inflammatory activity, and prevents CVDs. However, the clinical application of curcumin was limited due to its low bioavailability. This study aimed to investigate the ameliorative effects of chitosan-encapsulated curcumin (CEC) on heart and kidney damages in streptozotocin-induced type-1 diabetes C57BL/6 mice model. The results showed that Cur- and CEC-treatments downregulated the blood sugar and total cholesterol level as well as enhanced insulin secretion. However, blood pressure, triglycerides content, and very low-density lipoprotein-cholesterol content were not changed. Histochemistry analysis revealed that both curcumin and chitosan-encapsulated curcumin ameliorated cell hypertrophy and nucleus enlargement in the left ventricular of heart and reduced fibrosis in the kidney, especially after the chitosan-encapsulated curcumin treatment. Our study suggested that chitosan can effectively enhance the protective effect of curcumin on the heart and kidney damages in type-1 diabetes mice model.

scholarly journals Increased left ventricular extracellular volume and enhanced twist function in type 1 diabetic individuals

2017 ◽  
Vol 123 (2) ◽  
pp. 394-401 ◽  
Author(s):  
Zainisha Vasanji ◽  
Ronald J. Sigal ◽  
Neil D. Eves ◽  
Debra L. Isaac ◽  
Matthias G. Friedrich ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Shear Strain ◽  
Diabetic Cardiomyopathy ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Extracellular Volume Fraction ◽  
Left Ventricular ◽  
Lv Function ◽  
Reactive Fibrosis

Individuals with type 1 diabetes (T1D) characteristically have high glycemic levels that over time can result in reactive fibrosis and abnormalities in myocardial function. T1 mapping with magnetic resonance imaging (MRI) can estimate the extent of reactive fibrosis by measurement of the extracellular volume fraction (ECV). The extent of alterations in the ECV and associated changes in left ventricular (LV) function and morphology in individuals with T1D is unknown. Fourteen individuals with long-term T1D and 14 sex-, age-, and body mass index-matched controls without diabetes underwent MRI measurement of myocardial T1 and ECV values as well as LV function and morphology. Ventricular mass, volumes, and global function (LVEF and circumferential/longitudinal/radial strain) were similar in those with T1D and controls. However, those with T1D had larger myocardial ECV (22.1 ± 1.8 vs. 20.1 ± 2.1, P = 0.008) and increased native (noncontrast) myocardial T1 values (1,211 ± 44 vs. 1,172 ± 43 ms, P < 0.001) as compared with controls. Both the ECV and native T1 values significantly correlated with several components of torsion and circumferential-longitudinal shear strain ( Ecl, the shear strain component associated with twist). Individuals with T1D had increased systolic torsion ( P = 0.035), systolic torsion rate ( P = 0.032), peak Ecl ( P = 0.001), and rates of change of systolic ( P = 0.007) and diastolic ( P = 0.007) Ecl. Individuals with T1D, with normal structure, LVEF, and strain, have increased extracellular volume and increased native T1 values with associated augmented torsion and Ecl. These measures may be useful in detecting the early stages of diabetic cardiomyopathy and warrant larger prospective studies. NEW & NOTEWORTHY Individuals with type 1 diabetes, with normal left ventricular structure and function (ejection fraction and strain), have signs of interstitial fibrosis, measured with MRI as increased extracellular volume fraction and increased native myocardial T1, which significantly correlated with a number of measures of augmented left ventricular twist function. These measures may be useful in detecting the early stages of diabetic cardiomyopathy.

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