scholarly journals Ketone Ester D‐β‐Hydroxybutyrate‐(R)‐1,3 Butanediol Prevents Decline in Cardiac Function in Type 2 Diabetic Mice

Author(s):  
Phung N. Thai ◽  
Charles V. Miller ◽  
M. Todd King ◽  
Saul Schaefer ◽  
Richard L. Veech ◽  
...  

Background Heart failure is responsible for approximately 65% of deaths in patients with type 2 diabetes mellitus. However, existing therapeutics for type 2 diabetes mellitus have limited success on the prevention of diabetic cardiomyopathy. The aim of this study was to determine whether moderate elevation in D‐β‐hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus. Methods and Results Type 2 diabetic (db/db) and their corresponding wild‐type mice were fed a control diet or a diet where carbohydrates were equicalorically replaced by D‐β‐hydroxybutyrate‐(R)‐1,3 butanediol monoester (ketone ester [KE]). After 4 weeks, echocardiography demonstrated that a KE diet improved systolic and diastolic function in db/db mice. A KE diet increased expression of mitochondrial succinyl‐CoA:3‐oxoacid‐CoA transferase and restored decreased expression of mitochondrial β‐hydroxybutyrate dehydrogenase, key enzymes in cardiac ketone metabolism. A KE diet significantly enhanced both basal and ADP‐mediated oxygen consumption in cardiac mitochondria from both wild‐type and db/db animals; however, it did not result in the increased mitochondrial respiratory control ratio. Additionally, db/db mice on a KE diet had increased resistance to oxidative and redox stress, with evidence of restoration of decreased expression of thioredoxin and glutathione peroxidase 4 and less permeability transition pore activity in mitochondria. Mitochondrial biogenesis, quality control, and elimination of dysfunctional mitochondria via mitophagy were significantly increased in cardiomyocytes from db/db mice on a KE diet. The increase in mitophagy was correlated with restoration of mitofusin 2 expression, which contributed to improved coupling between cytosolic E3 ubiquitin ligase translocation into mitochondria and microtubule‐associated protein 1 light chain 3–mediated autophagosome formation. Conclusions Moderate elevation in circulating D‐β‐hydroxybutyrate levels via KE supplementation enhances mitochondrial biogenesis, quality control, and oxygen consumption and increases resistance to oxidative/redox stress and mPTP opening, thus resulting in improvement of cardiac function in animals with type 2 diabetes mellitus.

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Lee ◽  
J Zhou ◽  
CL Guo ◽  
WKK Wu ◽  
WT Wong ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Acute myocardial infarction (AMI) and sudden cardiac death (SCD) are major cardiovascular adverse outcomes in patients with type 2 diabetic mellitus. Although there are many risk scores on composite outcomes of major cardiovascular adverse outcomes or cardiovascular mortality for diabetic patients, these existing scores did not account for the difference in pathogenesis and prognosis between acute coronary syndrome and lethal ventricular arrhythmias. Furthermore, recent studies reported that HbA1c and lipid levels, which were often accounted for in these risk scores, have J/U-shaped relationships with adverse outcomes. Purpose The present study aims to evaluate the application of incorporating non-linear J/U-shaped relationships between mean HbA1c and cholesterol levels into risk scores for predicting for AMI and non-AMI related SCD respectively, amongst type 2 diabetes mellitus patients. Methods This was a territory-wide cohort study of patients with type 2 diabetes mellitus above the age 40 and free from prior AMI and SCD, with or without prescriptions of anti-diabetic agents between January 1st, 2009 to December 31st, 2009 at government-funded hospitals and clinics in Hong Kong. Risk scores were developed for predicting incident AMI and non-AMI related SCD. The performance of conditional inference survival forest (CISF) model compared to that of random survival forests (RSF) model and multivariate Cox model. Results This study included 261308 patients (age = 66.0 ± 11.8 years old, male = 47.6%, follow-up duration = 3552 ± 1201 days, diabetes duration = 4.77 ± 2.29 years). Mean HbA1c and high-density lipoprotein-cholesterol (HDL-C) were significant predictors of AMI under multivariate Cox regression and were linearly associated with AMI. Mean HbA1c and total cholesterol were significant multivariate predictors with a J-shaped relationship with non-AMI related SCD. The AMI and SCD risk scores had an area-under-the-curve (AUC) of 0.666 (95% confidence interval (CI)= [0.662, 0.669]) and 0.677 (95% CI= [0.673, 0.682]), respectively. CISF significantly improves prediction performance of both outcomes compared to RSF and multivariate Cox models. Conclusions A holistic combination of demographic, clinical, and laboratory indices can be used for the risk stratification of type 2 diabetic patients against AMI and SCD.


2017 ◽  
Vol 125 (09) ◽  
pp. 598-602 ◽  
Author(s):  
Zihang Wang ◽  
Yuhong Zhang ◽  
Weiwei Liu ◽  
Benli Su

AbstractThe present study aimed to evaluate the diagnostic value of echocardiography in measuring the thickness of epicardial adipose tissue (EAT) of the patients of type 2 diabetes mellitus (T2DM) and its correlation with the intimal-medial thickness of the carotid artery (cIMT) to investigate the relationship between EAT and cIMT. 68 patients of T2DM were enrolled and were divided into 2 groups: group of T2DM with duration≤10 years (35 cases) and group of T2DM with duration>10 years (33 cases). And 30 healthy subjects were enrolled as the control group. The thickness of EAT and cIMT were measured by echocardiography and high-frequency ultrasonography. The thickness of EAT and IMT of the carotid artery of 2 type 2 diabetic groups (duration≤10 years and>10 years) were significantly higher than that of the control group (all p<0.05), and the thickness of EAT and cIMT of the group of T2DM with duration>10 years were significantly higher than that of the group of T2DM with duration≤10 years (p<0.05). In univariate analysis, the thickness of EAT was positively and significantly associated with age (r=0.412, p<0.05), BMI (r=0.566, p<0.05), waist circumference (r=0.475, p<0.05), LDL (r=0.425, p<0.05), TG (r=0.496, p<0.05), duration of diabetes (r=0.384, p<0.05) and cIMT (r=0.456, p<0.05). In multiple stepwise regression analyses, age, BMI and IMT of carotid artery were appeared to be significantly associated with EAT (p<0.05 for all). In conclusion, routine screening of EAT and cIMT by ultrasonography in type 2 diabetic patients helps us to predict cardiovascular risks and prevent further development of cardiovascular complications.


2021 ◽  
Vol 8 (37) ◽  
pp. 3334-3338
Author(s):  
Satish Kumar

BACKGROUND Type 2 diabetes mellitus is common in the Indian population and awareness regarding the disease and its complications is low among the patients with diabetes. There is lack of studies regarding awareness of complications of diabetes among type 2 diabetic patients. The purpose of this study was to assess the awareness of diabetic complications among type 2 diabetic patients. METHODS This is an institutional based observational study. The sample comprised of 150 adult patients with type 2 diabetes mellitus who underwent treatment in the Department of Medicine, Medical College Kottayam and the patient’s age ranged from 18 - 77 years. RESULTS Majority of patients were in the age group 38 to 57 and the sample comprised of 56 % males and 44 % female patients. Out of 150 patients involved in the study, 120 patients (80 %) were aware of the complications of diabetes mellitus. Among the male patients, 70 (83.33 %) and among females, 50 (75.75 %) were aware of the complications in diabetes. In the study sample, 92 (61.33 %) were aware of the foot problems, 120 patients (80 %) were aware of renal complications, 91 patients were aware regarding eye problems of diabetes, 38 (25.33 %) regarding development of hypertension, 62 (41.33 %) regarding heart attack, 42 (28 %) patients were aware regarding development of stroke and 78 patients (52 %) had awareness regarding occurrence of recurrent infections. CONCLUSIONS Awareness regarding diabetes and its complications is fairly good among the diabetic patients in Kerala. Awareness regarding all complications of diabetes was higher among males than females. Providing awareness to type 2 diabetic patients by various educational programs may be of further help to prevent complications and to decrease the mortality and morbidity in type 2 diabetes patients. KEYWORDS Awareness, Diabetes


2019 ◽  
Vol 6 (3) ◽  
pp. 786
Author(s):  
Eda Dayakar ◽  
C. Sathya Sree ◽  
E. Sanjay

Background: Diabetes mellitus is a common health problem globally. Dyslipidaemia is a major risk factor to develop cardiovascular disease in diabetics. They present study was undertaken to find out the prevalence of dyslipidaemia in type 2 diabetic patients.Methods: The present study was a cross sectional study consisting of 46 (23 male and 23 female) known type 2 diabetes mellitus patients. Age, gender, duration of diabetes, body mass index (BMI) was recorder in all the diabetic patients.  Fasting blood glucose levels, total cholesterol, triglycerides, HDL, LDL, VLDL levels were measured using standard methods and recorded.Results: The average total cholesterol, triglycerides, LDL, HDL and VLDL were 200±42mg/dl, 169.62±89.79mg/dl, 132.45±36.38mg/dl,39.1±16.6mg/dl and 35.85±17.09mg/dl respectively. The incidence of occurrence of hypercholesterolemia was 58.6% and hypertriglyceridemia 36.9%. Increased levels of LDL were observed in 30 (65.2%) patients and reduced HDL was observed in 43 (93.4%) patients. The incidence rate of dyslipidaemia was higher in female diabetic patients when compared to male diabetic patients.Conclusions: Awareness on the dyslipidaemia and its risk factors should be provided to the type 2 diabetic patients as they are more prone to get cardiovascular disease and lipid profile also should be monitored regularly along with blood glucose levels.


2021 ◽  
pp. 187-188
Author(s):  
Ajay Jain ◽  
Debina sarkar ◽  
G.G. Kaushik ◽  
Ankita Sharma

Background: Type-2 diabetes mellitus (T2DM) is a progressive and chronic disease characterized by both β-cell dysfunction and increased insulin resistance. Diabetes mellitus is now considered a giant killer disease of the 21st century with its vicious prongs in the South-East Asian countries, specially India, which is rightly said to be the ''Diabetes Capital'' of the world. Vitamin D has important effects on insulin action, and may impact on a number of pathways which may be of importance in the development of type 2 diabetes mellitus. Materials & Methods: In this study 62 Type-2 diabetic patients, 62 healthy controls were enrolled. Biochemical analytes measured were Serum glucose (Fasting Blood Sugar & Post Prandial Blood Sugar), Glycosylated Haemoglobin, Serum Vitamin-D. Results: The mean Serum Vitamin-D in Type-2 diabetic subjects were (16.3 ±3.0) while in healthy subjects(controls) the values were (39.3±5.2) respectively. These values were found to be statistically highly signicant(p<0.001). Conclusion: Serum Vitamin-D levels were decreased in Type 2 diabetic subjects as compared to the values in healthy subjects(controls).


2019 ◽  
Vol 18 (2) ◽  
pp. 211-215
Author(s):  
Bimal K Agrawal ◽  
Parul Jain ◽  
Saurabh Marwaha ◽  
Richa Goel ◽  
Himanshu D Kumar ◽  
...  

Objective: Diabetic cardiomyopathy (DC) is a myocardial disease characterized by myocyte hypertrophy, interstitial fibrosis, protein glycosylation and intra-myocardial micro-angiopathy due to prolonged exposure of myocardial tissues to hyperglycemia in diabetes mellitus (DM) patients. Alteration in cardiac function can be non-invasively assessed via echocardiography. The early recognition of cardiac dysfunction can prevent the symptomatic heart failure in DM patients. The study aimed at evaluating cardiac function in uncomplicated type 2 diabetes mellitus. Materials And Methods: Sixty Type 2 DM patients without any feature of the coronary arterial disease (CAD), hypertension, nephropathy and respiratory illness were enrolled in the study and compared with the sixty age matched healthy controls. Echocardiographic assessment was done in all subjects to evaluate the cardiac function. Results: Diastolic dysfunction was more common in diabetic patients when compared with normal healthy population. Systolic dysfunction progresses with age of the diabetic patient. Conclusion: Echocardiography is a simple noninvasive cost effective test for detecting cardiac dysfunction in Type 2 DM patients and should be applied to detect early Left ventricular(LV) dysfunction so that corrective measures may be initiated early and cardiac functions may be preserved for long. Bangladesh Journal of Medical Science Vol.18(2) 2019 p.211-215


2014 ◽  
Vol 6 (3) ◽  
pp. 33-37
Author(s):  
Pranav Kumar Raghuwanshi ◽  
Devendra Pratap Singh Rajput ◽  
Bhupendra Kumar Ratre ◽  
Roopesh Jain ◽  
Narmada Patel ◽  
...  

Background: Diabetes mellitus is a very common endocrinal disorders and incidence of thyroid dysfunction also rising in India and world over. Thyroid hormones directly control insulin secretion and insulin clearance. Diabetes also may affect the thyroid function to variable extent first at the level of hypothalamic control of TSH release and second at peripheral tissue by converting T4 to T3. Aims and Objectives: The present study was carried out aiming to evaluate thyroid dysfunction among type 2 diabetes mellitus patients. Material and Methods: Study included total 80 subjects. Thyroid dysfunction was evaluated by investigating the subjects for Total tri-iodo-thyronine (T3), Total thyroxine (T4) and thyroid stimulating hormone (TSH). Plasma glucose was estimated by- GOD-POD method and Thyroid profile was estimated by- CLIA (chemiluminescence immunoassay) system. Statistical analysis was performed using software statistical package for social sciences (SPSS) version 20, unpaired T test, Pearson’s correlation. Results: In type 2 diabetic patients the prevalence of hypothyroidism and subclinical hypothyroidism was found to be 4(10.00%) and 6(15.00%) respectively, while the prevalence of subclinical hyperthyroidism and hyperthyroidism was found to be 0(0.0%) and 1(2.5%) respectively. In non diabetic healthy subjects the prevalence of hypothyroidism and subclinical hypothyroidism was found to be 1(2.5%) and 3(7.5%) respectively while the prevalence of subclinical hyperthyroidism and hyperthyroidism was found to be 0(0.0%) and 0(0.0%) respectively. Conclusion: The prevalence of thyroid dysfunction was found to be higher in type 2 diabetes mellitus subjects as compared to non-diabetic subjects. DOI: http://dx.doi.org/10.3126/ajms.v6i3.10814Asian Journal of Medical Sciences Vol.6(3) 2015 33-37  


2009 ◽  
Vol 204 (2) ◽  
pp. 143-152 ◽  
Author(s):  
J Han ◽  
Y Q Liu

Pyruvate carboxylase (PC) activity is enhanced in the islets of obese rats, but it is reduced in the islets of type 2 diabetic rats, suggesting the importance of PC in β-cell adaptation to insulin resistance as well as the possibility that PC reduction might lead to hyperglycemia. However, the causality is currently unknown. We used obese Agouti mice (AyL) as a model to show enhanced β-cell adaptation, and type 2 diabetic db/db mice as a model to show severe β-cell failure. After comparison of the two models, a less severe type 2 diabetic Agouti-K (AyK) mouse model was used to show the changes in islet PC activity during the development of type 2 diabetes mellitus (T2DM). AyK mice were separated into two groups: mildly (AyK-M, blood glucose <250 mg/dl) and severely (AyK-S, blood glucose >250 mg/dl) hyperglycemic. Islet PC activity, but not protein level, was increased 1.7-fold in AyK-M mice; in AyK-S mice, islet PC activity and protein level were reduced. All other changes including insulin secretion and islet morphology in AyK-M mice were similar to those observed in AyL mice, but they were worse in AyK-S mice where these parameters closely matched those in db/db mice. In 2-day treated islets, PC activity was inhibited by high glucose but not by palmitate. Our findings suggest that islet PC might play a role in the development of T2DM where reduction of PC activity might be a consequence of mild hyperglycemia and a cause for severe hyperglycemia.


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