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.

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.

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.

scholarly journals The effects of exercise training versus intensive insulin treatment on skeletal muscle fibre content in type 1 diabetes mellitus rodents

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
David P. McBey ◽  
Michelle Dotzert ◽  
C. W. J. Melling
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Exercise Training ◽  
Muscle Fibre ◽  
Lipid Content ◽  
Fibre Type ◽  
Insulin Treatment ◽  
Type I

Abstract Background Intensive-insulin treatment (IIT) strategy for patients with type 1 diabetes mellitus (T1DM) has been associated with sedentary behaviour and the development of insulin resistance. Exercising patients with T1DM often utilize a conventional insulin treatment (CIT) strategy leading to increased insulin sensitivity through improved intramyocellular lipid (IMCL) content. It is unclear how these exercise-related metabolic adaptations in response to exercise training relate to individual fibre-type transitions, and whether these alterations are evident between different insulin strategies (CIT vs. IIT). Purpose: This study examined glycogen and fat content in skeletal muscle fibres of diabetic rats following exercise-training. Methods Male Sprague-Dawley rats were divided into four groups: Control-Sedentary, CIT- and IIT-treated diabetic sedentary, and CIT-exercised trained (aerobic/resistance; DARE). After 12 weeks, muscle-fibre lipids and glycogen were compared through immunohistochemical analysis. Results The primary findings were that both IIT and DARE led to significant increases in type I fibres when compared to CIT, while DARE led to significantly increased lipid content in type I fibres compared to IIT. Conclusions These findings indicate that alterations in lipid content with insulin treatment and DARE are primarily evident in type I fibres, suggesting that muscle lipotoxicity in type 1 diabetes is muscle fibre-type dependant.

scholarly journals Correlation between echocardiographic parameters of left ventricle and glycosylated hemoglobin in children with type 1 Diabetes Mellitus

2022 ◽  
Vol 3 (1) ◽  
pp. 44-52
Author(s):  
Valeriu ESANU ◽  
Ina PALII
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Left Ventricle ◽  
Type 1 Diabetes Mellitus ◽  
Wall Thickness ◽  
Structural Parameters ◽  
Glycosylated Hemoglobin ◽  
Left Ventricular ◽  
Systolic Volume

Introduction. Deterioration of left ventricular (LV) parameters in Diabetes Mellitus (DM) can occur in the absence of other heart problems. An association between glycosylated hemoglobin (HbA1c) and changes of the LV parameters in DM has been reported. However, data regarding this association model in children with Type 1 Diabetes Mellitus (T1DM) are limited. The purpose of the work was to investigate the association between HbA1c and the LV parameters in pediatric patients. Material and methods. The study was conducted on 28 children with T1DM ((aged 10 - 18 years, gender M (15)/F (13), duration ≥5 years). The clinical (standard medical examination) and paraclinical (biochemical dosage – HbA1c, echocardiography – LV functional and structural parameters) data was carried out. Statistical analysis  used the SPSS version 20. Results. The correlational study between the HbA1c and the LV parameters revealed a statistically significant positive correlation coefficient with aortic root diameter (mm) (r=0.7**, p<0.001), left atrium (mm) (r=0.8**, p<0.001 LV diastolic diameter (mm) (r=0.7**, p<0.001), LV systolic diameter (mm) (r=0.7**, p<0.001), septal wall thickness (mm) (r=0.5*, p=0.036), posterior wall thickness (mm) (r=0.5*, p=0.032), LV diastolic volume (ml) (r=0.5*, p=0.025), LV systolic volume (ml) (r=0.6**, p=0.01), ejection fraction (%) (r=0.7**, p=0.001), fractional shortening (%) (r=0.6**, p=0.002). Conclusions. The results of the study show that in children with T1DM, the increase value of the HbA1c is associated with a consensual and proportional increase in the values of the parameters of the left ventricle.  

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 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.

Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type I diabetes

1992 ◽  
Vol 82 (3) ◽  
pp. 291-299 ◽  
Author(s):  
Peter A. Rutherford ◽  
Trevor H. Thomas ◽  
Susan J. Carr ◽  
Roy Taylor ◽  
Robert Wllklnson
Keyword(s):  
Type 1 Diabetes ◽  
Essential Hypertension ◽  
Type I Diabetes ◽  
Plasma Lipid ◽  
Maximum Velocity ◽  
Diabetic Patients ◽  
Type I ◽  
High Sodium ◽  
Type 1 Diabetic Patients

1. Increased erythrocyte sodium-lithium countertransport activity has been reported to be associated with nephropathy in type 1 diabetes and linked to a family history of essential hypertension. 2. This study aimed to determine the mechanism of increased sodium-lithium countertransport activity. Sodium-lithium countertransport kinetics were measured in uncomplicated and hyperlipidaemic type 1 diabetic patients. 3. In the nine out of 31 uncomplicated type 1 diabetic patients who had high sodium-lithium countertransport activity, the sodium affinity (Km) was normal but the maximum velocity (Vmax.) was increased. 4. Hyperlipidaemia, when present in diabetic patients, was associated with increased sodium-lithium countertransport activity, but could not explain the high activity in uncomplicated type 1 diabetic patients in whom plasma lipid concentrations were normal. 5. Sodium-lithium countertransport activity is increased in type 1 diabetes by a mechanism different to that in essential hypertension, where the mechanism is a low Km (increased sodium affinity). Hence familial hypertension cannot explain the raised sodium-lithium countertransport activity in type 1 diabetes.

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