Abstract 111: Paradoxical Exacerbation of Arrhythmias by the Cardioprotective Mitochondrial K-ATP Channel Agonist Diazoxide in Type 2 Diabetes Mellitus

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Chaoqin Xie ◽  
Basil S Karam ◽  
Fadi G Akar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Anion Channel ◽  
Sprague Dawley ◽  
Control Groups ◽  
And Control

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular complications including ischemia reperfusion injury (IR). Activation of mitochondrial KATP channels by Diazoxide (DZX) promotes beta cell rest and suppresses glucose production in patients. We hypothesized that DZX prevents IR arrhythmias in T2DM owing to its dual cardioprotective & antidiabetic property. Methods: Obese Zucker Diabetic Fatty (ZDF) rats (n=17) with established T2DM were studied. Control groups consisted of lean ZDF (n=6) and normal Sprague Dawley (n=10) rats. High resolution optical action potential (AP) mapping was performed in hearts before and after challenge with no flow ischemia for 12min followed by reperfusion. Results: Basal properties including rate dependence of conduction velocity (CV) and AP duration (APD) were not significantly (p=NS) altered in T2DM. Remarkably, ischemia uncovered major differences between groups as APD in T2DM failed to adapt to the ischemic challenge. Unlike APD, CV was reduced in all groups. DZX paradoxically promoted arrhythmias as all DZX (30uM) treated T2DM hearts exhibited ischemia related VT. In contrast, untreated T2DM (0/5) and control (0/9) hearts did not exhibit VT during ischemia. Underlying arrhythmic vulnerability of DZX treated T2DM hearts was a pronounced reduction (by 75% p<0.01) of the cardiac wavelength (WL) caused by accelerated APD shortening in response to ischemia. Upon reperfusion, T2DM and control groups exhibited a high (60% T2DM vs 44% control, p=NS) rate of VT, although the VT cycle length in T2DM was significantly longer (72 vs 44ms, p<0.01) suggesting a more adverse substrate modification by IR injury. Blocking the inner membrane anion channel (IMAC) fully abrogated reperfusion VT in T2DM. Conclusion: Ischemia uncovers a paradoxical resistance of T2DM hearts to APD adaptation. DZX reverses this property resulting in accelerated APD & WL shortening. This promotes reentrant VT during ischemia. Therefore, the anti-diabetic agent DZX should be avoided in T2DM patients at risk of ischemic events. Instead IMAC is an effective antiarrhythmic target for these patients.

Expression profiles of long noncoding RNAs in type 2 diabetes mellitus rat associated with the progression of ischemia-reperfursion injury

2020 ◽  
Author(s):  
Wenhao Song ◽  
Yao Gong ◽  
Pei Tu ◽  
Lin Zhang ◽  
Zhili Jin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Myocardial Ischemia Reperfusion

Abstract Background The aim of this study was to analyze the expressions of long noncoding RNA(lncRNA) in rat with type 2 diabetes mellitus(T2DM) complicated with acute myocardial ischemia reperfusion injury(IRI). Methods Type 2 diabetic rats were induced by high calorie diet combined with streptozotocin. IRI rats models were established by the ligation and release of left anterior descending coronary artery(LAD). The expression levels of lncRNA and mRNA in myocardial tissues of rats were detected via high-throughput sequencing technology, and Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Result Transcriptome analyses were performed to show expression profiles of mRNAs and lncRNAs in myocardial tissues of diabetic rats with IRI. A total of 2,476 lncRNAs and 710 mRNAs were differentially expressed between operation group and sham operation group. Then, an mRNA-lncRNA coexpression network was constructed. Finally, the present study verified that TCONS_00036439、TCONS_00151548、TCONS_00153276、TCONS_00344188、TCONS_00277692、TCONS_00236469、TCONS_00236468、TCONS_00153290、TCONS_00360941、TCONS_00142622 were associated with the initiation and development of ischemia reperfusion injury. Then, an lncRNA-mRNA coexpression network was constructed. Conclusion There is differential expression of lncRNAs in myocardial IRI tissues of diabetic rats. Building gene regulation networks to find the nodal gene and lncRNA is useful for understanding the pathogenesis of type 2 diabetes mellitus complicated with acute myocardial ischemia reperfusion injury and providing new therapy target.

scholarly journals Telomere length and vascular wall in patients with Type 2 Diabetes Mellitus

2014 ◽  
Vol 17 (3) ◽  
pp. 31-38 ◽  
Author(s):  
Ekaterina Nailyevna Dudinskaya ◽  
Olga Nikolaevna Tkacheva ◽  
Marina Vladimirovna Shestakova ◽  
Natalya Vasilyevna Brailova ◽  
Irina Dmitrievna Strazhesko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Carbohydrate Metabolism ◽  
Telomere Length ◽  
Vascular Wall ◽  
Vascular Changes ◽  
Control Groups ◽  
And Control

Aim. To study the relationship between changes in the artery structure and function and peripheral lymphocyte telomere length in patients with type 2 diabetes mellitus (DM2). Materials and methods. A total of 50 patients with T2DM and without clinical manifestations of cardiovascular disease (CVD) were included in the study; the control group consisted of 49 people. The following tests were conducted for all study participants: carbohydrate metabolism evaluation, carotid artery duplex scan to measure intima?media complex thickness (IMT) and to determine the presence of atherosclerotic plaques, carotid?femoral pulse wave velocity (PWV) measurement and lymphocyte telomere length measurement. Results. The vascular changes were more pronounced in patients with T2DM than in controls. The telomeres were shorter in patients with T2DM than in those without diabetes (9.53?0.1 vs 9.86?0.1, p=0.033). The participants were divided according to the telomere length. Among patients with T2DM, there were significant differences in the condition of the vascular wall [PWV: 10.58?0.1 m/s in patients with ?long? telomeres and 15.08?1.3 m/s in patients with ?short? telomeres; IMT: 0.80?0.09 mm in patients with ?long? telomeres and 0.87?0.05 mm in patients with ?short? telomeres (p=0.024)]. There were no significant differences in the arterial structure between the patient and control groups with ?long? telomeres [PWV: 10.58?0.1 m/s vs 10.5?0.5 m/s (p=0.913); IMT: 0.080?0.09 mm vs 0.73?0.03 mm (p=0.12). However, there were significant differences in the vascular wall condition between the patient and control groups with ?short? telomeres [PWV: 15.08?1.3 m/s vs, 10.7?0.5 m/s (p=0.015); IMT: 0.87?0.1 vs 0.78?0.1 (p=0.03)]. Conclusions. The signs of vascular ageing were more pronounced in patients with T2DM than in controls. However, despite diabetes, vascular changes were minimal in patients with ?long? lymphocyte telomeres, comparable with the state of the vascular walls in healthy individuals. Thus, enhanced lymphocyte telomere length may have a protective effect on the vascular wall and may prevent damage from carbohydrate metabolism disorders.

scholarly journals Correlation between Microalbuminuria and Glucose/ Leptin ratio in a sample of Iraqi patients with type 2 diabetes mellitus

2012 ◽  
Vol 6 (2) ◽  
pp. 42-49
Author(s):  
Rayah Sulaiman Baban ◽  
Zeina Ismael Ibrahem ◽  
Isam Noori Al-Karawi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Glucose ◽  
Fasting Serum ◽  
Control Groups ◽  
Normal Range ◽  
Serum Leptin ◽  
And Control

o study the association of serum leptin and glucose/leptin ratio with microalbuminuria in patients with type 2 diabetes mellitus at different durations, and to predict their effect on their renal function. A case control study was conducted in the International Diabetic Center at Al-Mustansiryia University in Baghdad-Iraq from 1st September 2008 to the 30th of July 2010. One hundred and eight male patients with type 2 diabetes mellitus (DM) were introduced in this study. Fifty three healthy subjects were used as a control. Fasting serum glucose, insulin, leptin, urea, creatinine and body mass index were estimated in both patient and control groups. Fifty three 49.07% out of 108 were diabetic for ≤2 years, while 55 patient 50.93% were diabetic >2 years. All patients were obese while healthy control subjects were not. Fasting serum glucose, insulin and leptin levels were found elevated in patients group while in control group their levels were found within normal range. Both urea and creatinine were also within the normal range for patients and control groups. Level of albumin in urine of patients with diabetes mellitus for ≤ 2years was found normal while in those with 3 to 6 or more than 6 years of DM, level of urinary albumin was found within the micro rang. A positive correlation with highly significant p value (<0.01) was found between patients (≤ 2 years and >2 years) serum leptin, glucose/leptin ratio and microalbuminuria. Conclusions: a strong association was found between serum leptin and glucose/leptin ratio with microalbuminuria in type 2 diabetic patients which can be used to predict the efficiency of their renal function at different durations and can be used as additional marker for the diagnosis of early stage of nephropathy.

scholarly journals Drift of the Subgingival Periodontal Microbiome during Chronic Periodontitis in Type 2 Diabetes Mellitus Patients

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 504
Author(s):  
Irina P. Balmasova ◽  
Evgenii I. Olekhnovich ◽  
Ksenia M. Klimina ◽  
Anna A. Korenkova ◽  
Maria T. Vakhitova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Relative Abundance ◽  
Chronic Periodontitis ◽  
Control Group ◽  
Control Groups ◽  
And Control ◽  
Pooled Samples

Since periodontitis and type 2 diabetes mellitus are complex diseases, a thorough understanding of their pathogenesis requires knowing the relationship of these pathologies with other disorders and environmental factors. In this study, the representability of the subgingival periodontal microbiome of 46 subjects was studied by 16S rRNA gene sequencing and shotgun sequencing of pooled samples. We examined 15 patients with chronic periodontitis (CP), 15 patients with chronic periodontitis associated with type 2 diabetes mellitus (CPT2DM), and 16 healthy subjects (Control). The severity of generalized chronic periodontitis in both periodontitis groups of patients (CP and CPT2DM) was moderate (stage II). The male to female ratios were approximately equal in each group (22 males and 24 females); the average age of the subjects was 53.9 ± 7.3 and 54.3 ± 7.2 years, respectively. The presence of overweight patients (Body Mass Index (BMI) 30–34.9 kg/m2) and patients with class 1–2 obesity (BMI 35–45.9 kg/m2) was significantly higher in the CPT2DM group than in patients having only chronic periodontitis or in the Control group. However, there was no statistically significant difference in all clinical indices between the CP and CPT2DM groups. An analysis of the metagenomic data revealed that the alpha diversity in the CPT2DM group was increased compared to that in the CP and Control groups. The microbiome biomarkers associated with experimental groups were evaluated. In both groups of patients with periodontitis, the relative abundance of Porphyromonadaceae was increased compared to that in the Control group. The CPT2DM group was characterized by a lower relative abundance of Streptococcaceae/Pasteurellaceae and a higher abundance of Leptotrichiaceae compared to those in the CP and Control groups. Furthermore, the CP and CPT2DM groups differed in terms of the relative abundance of Veillonellaceae (which was decreased in the CPT2DM group compared to CP) and Neisseriaceae (which was increased in the CPT2DM group compared to CP). In addition, differences in bacterial content were identified by a combination of shotgun sequencing of pooled samples and genome-resolved metagenomics. The results indicate that there are subgingival microbiome-specific features in patients with chronic periodontitis associated with type 2 diabetes mellitus.

Echinops Spp. Polysaccharide B Ameliorates Metabolic Abnormalities in a Rat Model of Type 2 Diabetes Mellitus

2020 ◽  
Vol 19 (1) ◽  
pp. 106-114
Author(s):  
Guang Hao ◽  
Xiaoyu Ma ◽  
Mengru Jiang ◽  
Zhenzhen Gao ◽  
Ying Yang
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Insulin Receptor ◽  
Skeletal Muscles ◽  
Insulin Receptor Substrate ◽  
Sprague Dawley

This study examined the in vivo effects of Echinops spp. polysaccharide B on type 2 diabetes mellitus in Sprague-Dawley rats. We constructed a type 2 diabetes mellitus Sprague-Dawley rat models by feeding a high-fat and high-sugar diet plus intraperitoneal injection of a small dose of streptozotocin. Using this diabetic rat model, different doses of Echinops polysaccharide B were administered orally for seven weeks. Groups receiving Xiaoke pill and metformin served as positive controls. The results showed that Echinops polysaccharide B treatment normalized the weight and blood sugar levels in the type 2 diabetes mellitus rats, increased muscle and liver glycogen content, improved glucose tolerance, increased insulin secretion, and reduced glucagon and insulin resistance indices. More importantly, Echinops polysaccharide B treatment upregulated the expression of insulin receptor in the liver, skeletal muscles, and pancreas, and significantly improved the expression levels of insulin receptor substrate-2 protein in the liver and pancreas, as well as it increased insulin receptor substrate-1 expression in skeletal muscles. These two proteins play crucial roles in increasing insulin secretion and in controlling type 2 diabetes mellitus. The findings of the present study suggest that Echinops polysaccharide B could improve the status of diabetes in type 2 diabetes mellitus rats, which may be achieved by improving insulin resistance. Our study provides a new insight into the development of a natural drug for the control of type 2 diabetes mellitus.

Epidemiology of Hypertension and Diabetes Mellitus in Latin America

2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Latin America ◽  
Cardiovascular Diseases ◽  
Latin American ◽  
Premature Mortality ◽  
Increased Risk ◽  
And Control

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.

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