Empagliflozin significantly attenuates QTc prolongation in rats due to sotalol

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V.O Baris ◽  
B Dincsoy ◽  
E Gedikli ◽  
A Erdem

Abstract Introduction Sotalol (SOT) is a Class 3 antiarrhythmic drug and commonly used for various arrhythmia treatments. However; it can prolong QT interval and lead to malignant arrhythmias. Empagliflozin is a selective SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has been shown to have positive effects on cardiovascular outcomes. Since the effect of empagliflozin (EMPA) on potassium channel activation is not yet known, there is no recommendation for the concomitant use of these drugs. Purpose In this study, we aimed to evaluate possible protective effects of empagliflozin in sotalol induced QT prolongation. Materials and methods Twenty-four male Wistar Alba rats were randomized into four groups. The first (control) group (n: 6) received only serum physiologic (1ml) via orogastric gavage (OG). The second (EMPA) group (n: 6) received EMPA (10 mg/kg) via OG. The third (SOT) group (n: 6) received SOT (80 mg/kg) via OG. The fourth (EMPA+SOT) group (n: 6) received EMPA (10 mg/kg) and SOT (80 mg/kg) via OG. Under anesthesia; PR, QT intervals and heart rate (HR) were measured and QTc value was also calculated at second hour on lead II using electrocardiogram (ECG). Results In the SOT group; QT intervals, T wave durations and QTc values were found to be statistically longer than the control group, whereas HR was found to be lower than the control group (p<0.01). In the EMPA+SOT group; QT intervals, T wave durations and QTc values were significantly lower and HR was significantly higher compared to the SOT group (p<0.001, p<0.01, p<0.001, p<0.001 respectively) (Table) Conclusion In the present study, we detected that EMPA significantly ameliorates SOT induced QT prolongation. In addition to this, we have also shown that EMPA can be used safely with SOT in clinical practice. With more clinical trials, the routine use of EMPA may be suggested to prevent QTc prolongation in diabetic patients receiving SOT. Finally; our study indicates that EMPA can effect on potassium channels. Funding Acknowledgement Type of funding source: None

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
V Baris ◽  
E Gedikli ◽  
A B Dincsoy ◽  
A Erdem

Abstract Background Empagliflozin is a SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has positive effects on cardiovascular outcomes. Amitriptyline can be used in many clinical indications but leads to cardiotoxicity by causing QT prolongation. Aim Our aim in the present study is to observe the effect of the concomitant use of amitriptyline and empagliflozin together, which have an effect on sodium and calcium balance in myocytes, on QTc by using ECG. Materials and methods Twenty-four male Wistar-Albino rats were randomized into four groups. The control group received only serum physiologic (1ml) via orogastric gavage (OG). The EMPA group received empagliflozin (10 mg/kg) via OG. The AMT group received amitriptyline (100 mg/kg) via OG. The AMT+EMPA group (n: 6) received amitriptyline and empagliflozin at same dose. Under anesthesia; QT and QTC intervals were measured at baseline, first, and second hours. Results The differences in QT and QTc values between the AMT group and control group were observed from the 1nd hour (Table 1, Figure 1). It was detected that the measurements of the control group were within normal limits. In the control group, QT was 77.33±9.02 ms at the basal, 73.50±2.26 ms at the 1st hour, 78.17±6.18 ms at the 2nd hour. QTc calculation was 165.42±18.34±10.5 ms at the basal, 166.63±17.92 msat the 1st hour, 184.65±12.86 ms at the 2nd hour. ECG findings of the EMPA group were within normal limits and similar to the control group (Table 1). The durations of QT interval and QTc calculations were found to be statistically longer in the AMT group than the control group at the 1st and 2nd hour (p≤0.001). Empagliflozin significantly ameliorated AMT-induced QT and QTc prolongation. The durations of QT interval were significantly lower at first (p<0,001) and 2nd hours (p<0.01) in the AMT+EMPA group compared to the AMT group. Moreover, QTc calculation was significantly lower in the AMT+EMP group than the AMT group at 1st and 2nd hour (P<0.01) (Table 1). Electrocardiographic comparisons of all groups for one second within the second hour can be seen in Figure 2. Conclusion In the present study, we have detected that empagliflozin significantly ameliorates amitriptyline induced QT prolongation. This effect is probably due to the opposite effects of these two agents in the intracellular calcium balance. It's known that; toxic dose of amitriptyline increases the amount of Sarcoplasmic Ca and the calcium permeability of Ryanodine channels, decreases SERCA-mediated Ca-reuptake by decreasing the calcium binding capacity of calsequestrin, and these leads QTc prolongation. It has been shown that empagliflozin increases Ca reuptake by causing a significant increase in SERCA activity, and decreases Ca sparks by causing inhibition of Ryanodine activity. With more clinical trials, the routine use of empagliflozin may be suggested to prevent QTc prolongation in the diabetic patients receiving amitriptyline. FUNDunding Acknowledgement Type of funding sources: None. Table 1. QT, QTc durations and HR for groups Figure 1. ECG traces – a: CON, b: EMPA, c: AMT, d: AMT+EMP


Author(s):  
Shah Namrata Vinubhai ◽  
Pardeep Agarwal ◽  
Bushra Fiza ◽  
Ramkishan Jat

Background: Serum ferritin is known as an index for body iron stores also as an inflammatory marker and it is influenced by several disease. We were looking for a correlation between HbA1c and S. Ferritin in type 2 DM. Methodology: The present study a total of 150 participants were enrolled of which 100 were confirmed cases of Type 2 Diabetes Mellitus and rest 50 age and sex matched healthy subjects constituted the control group. All were screened for HbA1c, Fasting blood sugar, Post prandial blood sugar and S.Ferritin. Results: A highly significant variation and positive correlation was observed with respect to S.Ferritin and HbA1c levels. Mean S.Ferritin was high in the subgroup with poor glycemic control. Conclusion: The fasting, post prandial sugar levels, HbA1c and S.Ferritin were significantly higher in the diabetic subjects. This study shows a positive correlation between HbA1c and S. Ferritin levels. So we can conclude that in diabetic patients S. Ferritin may serve as an independent marker of poor glycemic and metabolic control. Keywords: Serum ferritin, Type 2 Diabetes Mellitus, HbA1c.


2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.


2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Freda Lalrohlui ◽  
Souvik Ghatak ◽  
John Zohmingthanga ◽  
Vanlal Hruaii ◽  
Nachimuthu Senthil Kumar

AbstractOver the last few decades, Mizoram has shown an increase in cases of type 2 diabetes mellitus; however, no in-depth scientific records are available to understand the occurrence of the disease. In this study, 500 patients and 500 healthy controls were recruited to understand the possible influence of their dietary and lifestyle habits in relation with type 2 diabetes mellitus. A multivariate analysis using Cox regression was carried out to find the influence of dietary and lifestyle factors, and an unpaired t test was performed to find the difference in the levels of biochemical tests. Out of 500 diabetic patients, 261 (52.3%) were males and 239 (47.7%) were females, and among the control group, 238 (47.7%) were males and 262 (52.3%) were females. Fermented pork fat, Sa-um (odds ratio (OR) 18.98), was observed to be a potential risk factor along with tuibur (OR 0.1243) for both males and females. Creatinine level was found to be differentially regulated between the male and female diabetic patients. This is the first report of fermented pork fat and tobacco (in a water form) to be the risk factors for diabetes. The unique traditional foods like Sa-um and local lifestyle habits like tuibur of the Mizo population may trigger the risk for the prevalence of the disease, and this may serve as a model to study other populations with similar traditional practices.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mohamed Farhan Nasser ◽  
Ahmad Jabri ◽  
Saima Karim ◽  
Elizabeth Kaufman

Introduction: QT prolongation is associated with increased risk of ventricular arrhythmias.As many patients with COVID19 may be started on QT prolonging drugs, measuring and monitoring QT is imperative to prevent fatal ventricular arrhythmias. However, we need to limit exposure of staff to patients with confirmed COVID19 and judiciously use personal protective equipment. Thus, it is important to find alternatives to doing frequent 12-lead ECGs. Hypothesis: We hypothesize that the QT interval measured from telemetry is similar to the QT interval on 12-lead ECG. Methods: Telemetry recordings and 12-lead ECGs were obtained from 15 patients at the same time and identical heart rates. Patients were from two different inpatient units with the same telemetry monitoring service. QT intervals were measured manually using calipers with the tangent method, excluding U waves. Telemetry recordings included lead I and II or a precordial lead. QT from telemetry was compared to the corresponding leads and to the longest QT on the 12-lead ECG. In cases of atrial fibrillation (AF), the QT from all the complexes was averaged. Results: Of 15 patients, 2 were in AF and 2 had RBBB. One patient had abnormal T-wave morphology and QT prolongation (abnormal repolarization). In all patients, QT intervals from the same leads as telemetry matched the QT measured from 12-lead. In 14 of 15 patients, telemetry QT matched the longest QT on the 12-lead ECG. However, in the patient with abnormal repolarization, maximum QT on 12-lead ECG was substantially longer than telemetry QT (Figure 1). Conclusion: When using the same lead, QT intervals were identical on telemetry and 12-lead ECG. However, in the patient with abnormal repolarization, the longest QT on 12-lead ECG was not represented on telemetry. In patients with abnormal repolarization on 12-lead ECG, we recommend serial 12-lead ECGs while on QT-prolonging drugs. Telemetry may suffice as a surrogate for 12-lead ECG to follow QT intervals in most patients.


Pteridines ◽  
2017 ◽  
Vol 28 (3-4) ◽  
pp. 177-183 ◽  
Author(s):  
Angel Fenol ◽  
V.R. Swetha ◽  
Sajitha Krishnan ◽  
Jayachandran Perayil ◽  
Rajesh Vyloppillil ◽  
...  

AbstractNeopterin is a novel predictor for coronary events especially in diabetic patients and also an indicator for the effectiveness of the periodontal treatment. In this study, we assessed whether salivary neopterin can be used as a potential biomarker in evaluating the risk of cardiovascular disease in type 2 diabetic patients with chronic periodontitis. Forty subjects between 25 and 75 years of age and who matched the criteria were selected and divided into four groups. Their periodontal status was evaluated. Stimulated whole saliva and blood were collected for analysis of salivary neopterin and fibrinogen and HbA1c levels, respectively. Nonsurgical periodontal therapy was carried out. Patients were recalled after 3 months, and the same procedure was repeated. A reduction in all the parameters was seen after treatment in all the four groups. Salivary neopterin levels showed significant difference (p<0.001) in the values between the study groups and the control group before treatment. After 3 months of treatment, salivary neopterin levels showed a statistical significant reduction (p<0.001) in all the study groups. Neopterin could serve as an effective tool to assess the inflammatory process related to periodontitis and diabetes mellitus and also predict future cardiovascular events in diabetic patients.


2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.


2016 ◽  
Vol 9 (5) ◽  
pp. 234
Author(s):  
Zahra Heidari ◽  
Zahra Sepehri ◽  
Aleme Doostdar

<p>In addition to known risk factors, the role of different micronutrients such as selenium in diabetes incidence has been proposed. Some previous studies have shown an association of selenium deficiency and type 2 diabetes mellitus, while other studies have not confirmed such a relationship. The aim of this study was to evaluate serum level of selenium in patients with Type 2 diabetes compared with the control group. This cross-sectional study was carried out on patients with type 2 diabetes in Zahedan, southeastern Iran. One hundred newly diagnosed type 2 diabetic patients were evaluated for serum selenium level. One hundred subjects from the general population who had normal fasting blood sugar levels were selected as the control group. The control group subjects were matched in pairs with each of patients on the basis of sex, age (± one year), and body mass index (±1). Serum level of selenium was determined by spectrometry method. Results were compared using t-test. The mean serum level of selenium in patients was 94.47±18.07 µg/L whereas in control group was 142.79±23.67 µg/L. The mean serum level of selenium was significantly different between the two groups (P&lt;0.001). Serum levels of selenium in diabetic patients with significant difference statistically were lower than the control group. In order to evaluate serum level of selenium in patients with diabetes, studies with larger sample size are required. Likewise, prospective studies along with selenium supplementation and investigating its effect on incidence of diabetes are accordingly needed.</p>


2020 ◽  
Vol 20 (2) ◽  
pp. 833-840
Author(s):  
Erhan Onalan ◽  
Yusuf Doğan ◽  
Ebru Onalan ◽  
Nevzat Gozel ◽  
Ilay Buran ◽  
...  

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.


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