scholarly journals The Role of SGLT2 Inhibitor on the Treatment of Diabetic Retinopathy

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Wenjun Sha ◽  
Song Wen ◽  
Lin Chen ◽  
Bilin Xu ◽  
Tao Lei ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Glucose Transporter ◽  
Early Stage ◽  
Sglt2 Inhibitor ◽  
Research Field ◽  
Research Progress ◽  
Diabetic Microangiopathy ◽  
Control Blood Glucose ◽  
Glucose Transporter 2 ◽  
Prevention And Treatment

Diabetic retinopathy (DR) is one of the most serious complications of diabetic microangiopathy. DR has an early onset and is not easy to detect. When visual impairment occurs, the optimal period for therapy is often missed. Therefore, the prevention and treatment of DR should start from the early stage of diabetes. Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) is a new antidiabetic drug which is mainly used in clinical practice to control blood glucose of patients with type 2 diabetes prone to develop chronic heart failure. Recent studies have found that SGLT2 is also expressed in the human retina. Now, the prevention and treatment of diabetic retinopathy with SGLT2i while reducing blood sugar has become a new research field. Hence, this article reviewed the recent therapeutic and research progress of SGLT2 in the treatment of diabetic retinopathy.

Euglycemic Diabetic Ketoacidosis in a Diabetic Patient Treated with SGLT2 Inhibitor

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lavrynenko O ◽  
◽  
Santos H ◽  
Garza A ◽  
Qazi R ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Diabetic Ketoacidosis ◽  
Glucose Transporter ◽  
Sglt2 Inhibitor ◽  
Anion Gap ◽  
Laboratory Evaluation ◽  
Intravenous Insulin ◽  
Glucose Transporter 2 ◽  
Life Threatening ◽  
History Of

Diabetic Ketoacidosis (DKA) is a life - threatening complication and must be diagnosed and treated promptly and aggressively. The classic triad of DKA is hyperglycemia (Blood Glucose (BG) >250mg/dl; anion gap metabolic acidosis (pH <7.30 and bicarbonate <18mEq/L); and ketonemia. With Food and Drug Administration (FDA) approval of the sodium - glucose transporter 2 inhibitors (SGLT2i), DKA can occur with BG levels below 200mg/dl and has been defined as Euglycemic DKA (EuDKA). Due to the absence of hyperglycemia, the diagnosis of EuDKA is challenging and often delayed. This 60-year-old diabetic male, treated with Empagliflozin and pioglitazone, presented with diarrhea and abdominal pain, which started 20 days ago. He was admitted with dehydration and diagnosis of colitis. On admission laboratory evaluation revealed metabolic acidosis with elevated anion gap of 18mEq/L, bicarbonate of 19mEq/L, and BG of 146mg/dL. There was no history of ingestion of alcohol, salicylates, methanol, ethylene glycol and nothing to suggest lactic acidosis. The plasma creatinine was 0.79mg/dl. On the following day, he developed an increase in the anion gap to 22mEq/L and further decrease in bicarbonate to 13mEq/L, and serum ketones were detected. The patient was treated for EuDKA in ICU with intravenous insulin, dextrose (to prevent hypoglycemia), and normal saline with resolution of his symptoms and EuDKA in 3 days. With the widespread use of SGLT2i, physicians need to have a high suspicion of EuDKA in patients who present with an unexplained anion gap acidosis without or only modest elevation in BG concentration.

scholarly journals Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

2020 ◽  
Vol 21 (21) ◽  
pp. 7833
Author(s):  
Yi-Chou Hou ◽  
Cai-Mei Zheng ◽  
Tzung-Hai Yen ◽  
Kuo-Cheng Lu
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Tone ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Clinical Evidence ◽  
Sglt2 Inhibitor ◽  
Cardiac Protection ◽  
Glucose Transporter 2 ◽  
Glucose Reabsorption ◽  
Molecular Aspects

The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.

scholarly journals SGLT2 inhibitors therapy protects glucotoxicity-induced β-cell failure in a mouse model of human KATP-induced diabetes trough mitigation of oxidative and ER stress

2021 ◽  
Author(s):  
Zeenat A. Shyr ◽  
Zihan Yan ◽  
Alessandro Ustione ◽  
Erin M. Egan ◽  
Maria S. Remedi
Keyword(s):  
Er Stress ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cell Mass ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Insulin Content ◽  
Β Cell ◽  
Glucose Transporter 2 ◽  
Β Cell Function

AbstractProgressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the mechanisms underlying and temporal progression of glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice developed severe diabetes followed by an unexpected loss of insulin content, decreased proinsulin processing and proinsulin accumulation at 2-weeks of diabetes. This was accompanied by a marked increase in β-cell oxidative and ER stress, without changes in islet cell identity. Strikingly, early treatment with the SGLT2 inhibitor dapagliflozin restored insulin content, decreased proinsulin:insulin ratio and reduced oxidative and ER stress. However, despite reduction of blood glucose, dapagliflozin therapy was ineffective in restoring β-cell function in NDM mice when tit was initiated at >40 days of diabetes, when loss of β-cell mass and identity had already occurred. These results have important clinical implications as they demonstrate that: i) hyperglycemia per se, and not insulin hypersecretion, drives β-cell failure in diabetes, ii) recovery of β-cell function by SGLT2 inhibitors is through reduction of oxidative and ER stress, iii) SGLT2 inhibitors revert/prevent β-cell failure when used in early stages of diabetes, but not when loss of β-cell mass/identity already occurred, iv) common execution pathways underlie loss and recovery of β-cell function in different forms of diabetes.

scholarly journals Combination Therapy with Empagliflozin and Insulin Results in Successful Glycemic Control: A Case Report of Uncontrolled Diabetes Caused by Autoimmune Pancreatitis and Subsequent Steroid Treatment

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Miyako Kishimoto ◽  
Kazuhide Yamaoki ◽  
Masayuki Adachi
Keyword(s):  
Magnetic Resonance ◽  
Glycemic Control ◽  
Autoimmune Pancreatitis ◽  
Glucose Transporter ◽  
Sglt2 Inhibitor ◽  
Insulin Dosage ◽  
Diabetic Patients ◽  
Total Dosage ◽  
Prednisolone Therapy ◽  
Glucose Transporter 2

A 66-year-old Japanese male presented with thirst, polyuria, and hemoglobin A1c and postprandial glucose levels (13.1% and 529 mg/dL, respectively) that indicated severe hyperglycemia. Based on his high immunoglobulin G4 level and the results of magnetic resonance imaging and magnetic resonance cholangiopancreatography, we diagnosed him with autoimmune pancreatitis. Insulin was initiated to control his diabetes. One month later, the patient commenced on prednisolone therapy for the treatment of autoimmune pancreatitis, after which his total insulin dosage increased to a maximum of 52 units/day. When the prednisolone dosage was later tapered, the patient’s total dosage of insulin was reduced to 42 units/day. However, he had gained 3.6 kg from the start of prednisolone therapy, and 42 units/day was insufficient for maintaining glycemic control. Thus, empagliflozin, a sodium-dependent glucose transporter 2 (SGLT2) inhibitor, was added. Thereafter, we were able to reduce the patient’s total dosage of insulin; it was eventually discontinued with good glycemic control and weight loss. Such results suggest that the combination of insulin with an SGLT2 inhibitor may be a viable option for the treatment of diabetic patients on prednisolone therapy.

scholarly journals Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma

2018 ◽  
Vol 10 (467) ◽  
pp. eaat5933 ◽  
Author(s):  
Claudio R. Scafoglio ◽  
Brendon Villegas ◽  
Gihad Abdelhady ◽  
Sean T. Bailey ◽  
Jie Liu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Glucose Transporter ◽  
Early Stage ◽  
Premalignant Lesions ◽  
Low Grade ◽  
Lung Tumorigenesis ◽  
Glucose Transporter 2 ◽  
Potential Marker

The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[18F] fluoro-alpha-d-glucopyranoside (Me4FDG), which specifically detects SGLT activity. Using a combination of immunohistochemistry and Me4FDG PET, we identified high expression and functional activity of SGLT2 in lung premalignancy and early-stage/low-grade LADC. Furthermore, selective targeting of SGLT2 with FDA-approved small-molecule inhibitors, the gliflozins, greatly reduced tumor growth and prolonged survival in autochthonous mouse models and patient-derived xenografts of LADC. Targeting SGLT2 in lung tumors may intercept lung cancer progression at early stages of development by pairing Me4FDG PET imaging with therapy using SGLT2 inhibitors.

Prevention and Treatment of Diabetic Retinopathy: Evidence from Clinical Trials and Perspectives

2011 ◽  
Vol 7 (3) ◽  
pp. 190-200 ◽  
Author(s):  
Manuela Abbate ◽  
Paolo Cravedi ◽  
Ilian Iliev ◽  
Giuseppe Remuzzi ◽  
Piero Ruggenenti
Keyword(s):  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Prevention And Treatment

Review of Various Tasks Performed in the Preprocessing Phase of a Diabetic Retinopathy Diagnosis System

2020 ◽  
Vol 16 (4) ◽  
pp. 397-426
Author(s):  
Muhammad Nadeem Ashraf ◽  
Muhammad Hussain ◽  
Zulfiqar Habib
Keyword(s):  
Diabetic Retinopathy ◽  
Blood Vessels ◽  
Early Stage ◽  
Spherical Shape ◽  
Cost Effective ◽  
Lesion Detection ◽  
Diabetic Patients ◽  
Cad System ◽  
Non Invasive ◽  
Optic Discs

Diabetic Retinopathy (DR) is a major cause of blindness in diabetic patients. The increasing population of diabetic patients and difficulty to diagnose it at an early stage are limiting the screening capabilities of manual diagnosis by ophthalmologists. Color fundus images are widely used to detect DR lesions due to their comfortable, cost-effective and non-invasive acquisition procedure. Computer Aided Diagnosis (CAD) of DR based on these images can assist ophthalmologists and help in saving many sight years of diabetic patients. In a CAD system, preprocessing is a crucial phase, which significantly affects its performance. Commonly used preprocessing operations are the enhancement of poor contrast, balancing the illumination imbalance due to the spherical shape of a retina, noise reduction, image resizing to support multi-resolution, color normalization, extraction of a field of view (FOV), etc. Also, the presence of blood vessels and optic discs makes the lesion detection more challenging because these two artifacts exhibit specific attributes, which are similar to those of DR lesions. Preprocessing operations can be broadly divided into three categories: 1) fixing the native defects, 2) segmentation of blood vessels, and 3) localization and segmentation of optic discs. This paper presents a review of the state-of-the-art preprocessing techniques related to three categories of operations, highlighting their significant aspects and limitations. The survey is concluded with the most effective preprocessing methods, which have been shown to improve the accuracy and efficiency of the CAD systems.

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

Two-Tier Grading System for NPDR Severities of Diabetic Retinopathy in Retinal Fundus Images

2020 ◽  
Vol 14 ◽  
Author(s):  
Charu Bhardwaj ◽  
Shruti Jain ◽  
Meenakshi Sood
Keyword(s):  
Diabetic Retinopathy ◽  
Statistical Analysis ◽  
Early Stage ◽  
Image Feature ◽  
Grading System ◽  
Fundus Images ◽  
Fundus Image ◽  
Retinal Fundus Images ◽  
Retinal Fundus ◽  
Timely Treatment

: Diabetic Retinopathy is the leading cause of vision impairment and its early stage diagnosis relies on regular monitoring and timely treatment for anomalies exhibiting subtle distinction among different severity grades. The existing Diabetic Retinopathy (DR) detection approaches are subjective, laborious and time consuming which can only be carried out by skilled professionals. All the patents related to DR detection and diagnoses applicable for our research problem were revised by the authors. The major limitation in classification of severities lies in poor discrimination between actual lesions, background noise and other anatomical structures. A robust and computationally efficient Two-Tier DR (2TDR) grading system is proposed in this paper to categorize various DR severities (mild, moderate and severe) present in retinal fundus images. In the proposed 2TDR grading system, input fundus image is subjected to background segmentation and the foreground fundus image is used for anomaly identification followed by GLCM feature extraction forming an image feature set. The novelty of our model lies in the exhaustive statistical analysis of extracted feature set to obtain optimal reduced image feature set employed further for classification. Classification outcomes are obtained for both extracted as well as reduced feature set to validate the significance of statistical analysis in severity classification and grading. For single tier classification stage, the proposed system achieves an overall accuracy of 100% by k- Nearest Neighbour (kNN) and Artificial Neural Network (ANN) classifier. In second tier classification stage an overall accuracy of 95.3% with kNN and 98.0% with ANN is achieved for all stages utilizing optimal reduced feature set. 2TDR system demonstrates overall improvement in classification performance by 2% and 6% for kNN and ANN respectively after feature set reduction, and also outperforms the accuracy obtained by other state of the art methods when applied to the MESSIDOR dataset. This application oriented work aids in accurate DR classification for effective diagnosis and timely treatment of severe retinal ailment.

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