scholarly journals How and why SGLT2 inhibitors should be explored as potential treatment option in diabetic retinopathy: clinical concept and methodology

2019 ◽  
Vol 10 ◽  
pp. 204201881989188 ◽  
Author(s):  
Marcus May ◽  
Theodor Framke ◽  
Bernd Junker ◽  
Carsten Framme ◽  
Amelie Pielen* ◽  
...  
Keyword(s):  
Treatment Option ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Sglt2 Inhibitors ◽  
Diabetic Microangiopathy ◽  
Potential Treatment ◽  
Treatment And Prevention ◽  
Clinical Complications ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Patients suffering from type 2 diabetes are at an increased risk of developing classical microvascular complications such as retinopathy, neuropathy, and nephropathy, which represent a significant health burden. Tight control of blood glucose, blood pressure, and serum cholesterol reduce the risk of microvascular complications but effective pharmacologically targeted treatment options for the treatment and prevention of diabetic microangiopathy are still lacking. Pharmacological inhibition of sodium glucose cotransporter 2 (SGLT2) might have the potential to directly protect against microvascular complications and could represent a potential treatment option. Randomized controlled clinical proof of concept trials are needed to investigate a potential central role of SGLT2 inhibitors in the prevention of diabetic microangiopathy and its classical clinical complications of retinopathy, neuropathy, and nephropathy.

scholarly journals Focusing on Sodium Glucose Cotransporter-2 and the Sympathetic Nervous System: Potential Impact in Diabetic Retinopathy

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Lakshini Y. Herat ◽  
Vance B. Matthews ◽  
P. Elizabeth Rakoczy ◽  
Revathy Carnagarin ◽  
Markus Schlaich
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Microvascular Complications ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Current Evidence ◽  
Therapeutic Approaches ◽  
Novel Therapy ◽  
Sodium Glucose Cotransporter ◽  
Major Treatment

The prevalence of diabetes is at pandemic levels in today’s society. Microvascular complications in organs including the eye are commonly observed in human diabetic subjects. Diabetic retinopathy (DR) is a prominent microvascular complication observed in many diabetics and is particularly debilitating as it may result in impaired or complete vision loss. In addition, DR is extremely costly for the patient and financially impacts the economy as a range of drug-related therapies and laser treatment may be essential. Prevention of microvascular complications is the major treatment goal of current therapeutic approaches; however, these therapies appear insufficient. Presently, sodium glucose cotransporter-2 (SGLT2) inhibitors may offer a novel therapy beyond simple glucose lowering. Excitingly, the EMPA-REG clinical trial, which focuses on the clinically used SGLT2 inhibitor empagliflozin, has been extremely fruitful and has highlighted beneficial cardiovascular and renal outcomes. The effects of SGLT2 inhibitors on DR are currently a topic of much research as outlined in the current review, but future studies are urgently needed to fully gain mechanistic insights. Here, we summarize current evidence and identify gaps that need to be addressed.

Ketoacidosis Due to Empagliflozin, a Paradigm Shift: Case Report and Review of Literature

2019 ◽  
Vol 15 (4) ◽  
pp. 259-262 ◽  
Author(s):  
Carlos Hernandez-Quiles ◽  
Nieves Ramirez-Duque ◽  
Domingo Acosta-Delgado
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Case Report ◽  
Paradigm Shift ◽  
Cardiovascular Events ◽  
Sglt2 Inhibitors ◽  
Review Of Literature ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Introduction: Sodium-glucose cotransporter 2(SGLT2)-inhibitors are new antihyperglycemic agents that have shown a reduction in cardiovascular events in type 2 diabetes mellitus. Recent warnings have been developed about an increased risk of euglycemic and moderate hyperglycemic diabetic ketoacidosis with the use of SGLT2 inhibitors, but its real incidence is not available yet. Case Report: We present a case of DKA with moderate hyperglycemia in a patient treated with metformin and empagliflozin. Conclusion: DKA in patients treated with SGLT2 inhibitors can be presented as euglycemic and moderated hyperglycemia. This special presentation poses a physician’s challenge.

scholarly journals Effect of sodium glucose cotransporter 2 inhibitors on cardiac function and cardiovascular outcome: a systematic review

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Koichiro Matsumura ◽  
Tetsuro Sugiura
Keyword(s):  
Diabetes Mellitus ◽  
Cardiac Function ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Sodium Reabsorption ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Underlying Mechanisms

Abstract A high incidence of left ventricular diastolic dysfunction and increased risk of cardiovascular events have been reported in patients with diabetes mellitus. Sodium glucose cotransporter 2 (SGLT2) inhibitors selectively inhibit kidney glucose and sodium reabsorption, and cardiovascular benefits of SGLT2 inhibitors beyond other antidiabetic drugs have been reported in type 2 diabetes mellitus (T2DM) clinical trials. However, underlying mechanisms contributing to the improvement of cardiovascular outcomes have not been clearly identified. In this review, likely mechanisms of SGLT2 inhibitors contributing to a favorable cardiovascular outcomes are discussed based on experimental and clinical studies on cardiac function.

scholarly journals Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Retinal Vein Occlusion Among Patients With Type 2 Diabetes: A Propensity Score–Matched Cohort Study

2021 ◽  
Author(s):  
Min-Kyung Lee ◽  
Bongsung Kim ◽  
Kyungdo Han ◽  
Jae-Hyuk Lee ◽  
Minhee Kim ◽  
...  
Keyword(s):  
Cohort Study ◽  
Propensity Score ◽  
Retinal Vein Occlusion ◽  
Sglt2 Inhibitors ◽  
Matched Cohort ◽  
Matched Cohort Study ◽  
Vein Occlusion ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Subgroup Analyses

<b>OBJECTIVE</b><b></b> <p>To assess the association between use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and retinal vein occlusion (RVO) using data from the National Health Insurance Service in South Korea.</p> <p><b>RESEARCH DESIGN AND METHODS</b><b></b></p> <p>We used an active comparator, new user design and nationwide data from 2014 to 2017. Based on a 1:1 propensity score match, we included 47 369 new users of SGLT2 inhibitors and 47 369 users of other glucose-lowering drugs (oGLD). In the matched sample, we used the Cox proportional hazards model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for developing RVO. Based on the main outcome, exploratory subgroup analyses were undertaken.</p> <p><b>RESULTS</b></p> <p>During the follow-up of 2.57 years, the incidence rate of RVO was 2.19 and 1.79 per 1000 person-years in patients treated with SGLT2 inhibitors and oGLD, respectively. The new use of SGLT2 inhibitors was associated with an increased risk of RVO compared with oGLD use (HR 1.264, 95% CI 1.056–1.513). In the subgroup analyses, a significant interaction with SGLT2 inhibitors was observed for <em>age and estimated glomerular filtration rate (eGFR);</em> the HR for RVO was higher in patients aged ≥ 60 years and those with eGFR <60 mL/min/1.73m<sup>2</sup> than in others.</p> <p><b>CONCLUSIONS</b></p> <p>In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of RVO. The older patients and those with chronic kidney disease were at higher risk for RVO. </p>

Successful treatment with secnidazole for trichomoniasis in the setting of metronidazole hypersensitivity

2021 ◽  
pp. 095646242110349
Author(s):  
Wesley D Kufel ◽  
Elizabeth A Asiago-Reddy ◽  
Katie A Parsels ◽  
Soma Sanyal ◽  
Jennifer L Coyne
Keyword(s):  
Infectious Disease ◽  
Effective Treatment ◽  
Treatment Option ◽  
Successful Treatment ◽  
Treatment Options ◽  
Cross Reactivity ◽  
Potential Treatment ◽  
History Of ◽  
Microbiological Cure ◽  
Disease Specialist

Limited effective treatment options currently exist for trichomoniasis management among patients with metronidazole hypersensitivity. We report a patient with a documented history of metronidazole hypersensitivity who initially was treated with nitazoxanide but demonstrated clinical and microbiological failure. Secnidazole was subsequently used for treatment, which resulted in clinical and microbiological cure without observation of cross-reactivity. Secnidazole may represent a potential treatment option for trichomoniasis in patients with metronidazole hypersensitivity after consultation with an infectious disease specialist.

scholarly journals Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Retinal Vein Occlusion Among Patients With Type 2 Diabetes: A Propensity Score–Matched Cohort Study

2021 ◽  
Author(s):  
Min-Kyung Lee ◽  
Bongsung Kim ◽  
Kyungdo Han ◽  
Jae-Hyuk Lee ◽  
Minhee Kim ◽  
...  
Keyword(s):  
Cohort Study ◽  
Propensity Score ◽  
Retinal Vein Occlusion ◽  
Sglt2 Inhibitors ◽  
Matched Cohort ◽  
Matched Cohort Study ◽  
Vein Occlusion ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Subgroup Analyses

<b>OBJECTIVE</b><b></b> <p>To assess the association between use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and retinal vein occlusion (RVO) using data from the National Health Insurance Service in South Korea.</p> <p><b>RESEARCH DESIGN AND METHODS</b><b></b></p> <p>We used an active comparator, new user design and nationwide data from 2014 to 2017. Based on a 1:1 propensity score match, we included 47 369 new users of SGLT2 inhibitors and 47 369 users of other glucose-lowering drugs (oGLD). In the matched sample, we used the Cox proportional hazards model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for developing RVO. Based on the main outcome, exploratory subgroup analyses were undertaken.</p> <p><b>RESULTS</b></p> <p>During the follow-up of 2.57 years, the incidence rate of RVO was 2.19 and 1.79 per 1000 person-years in patients treated with SGLT2 inhibitors and oGLD, respectively. The new use of SGLT2 inhibitors was associated with an increased risk of RVO compared with oGLD use (HR 1.264, 95% CI 1.056–1.513). In the subgroup analyses, a significant interaction with SGLT2 inhibitors was observed for <em>age and estimated glomerular filtration rate (eGFR);</em> the HR for RVO was higher in patients aged ≥ 60 years and those with eGFR <60 mL/min/1.73m<sup>2</sup> than in others.</p> <p><b>CONCLUSIONS</b></p> <p>In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of RVO. The older patients and those with chronic kidney disease were at higher risk for RVO. </p>

scholarly journals Efficacy of Particulated Juvenile Cartilage Allograft Transplantation for Osteochondral Lesions of the Talus

2017 ◽  
Vol 2 (3) ◽  
pp. 2473011417S0001
Author(s):  
Travis Dekker ◽  
Kamran Hamid ◽  
Mark Easley ◽  
John Steele ◽  
Samuel Adams
Keyword(s):  
Treatment Option ◽  
Treatment Options ◽  
Lesion Size ◽  
Osteochondral Lesions ◽  
Allograft Transplantation ◽  
Increased Risk ◽  
Prior Surgery ◽  
History Of ◽  
Male Sex

Category: Ankle, Arthroscopy, Basic Sciences/Biologics, Sports Introduction/Purpose: Symptomatic osteochondral lesions of the talus (OLTs) are difficult to treat. As such, a broad array of cartilage treatment options exist. Despite the various techniques, many patients require multiple procedures due to persistent pain, failure of cartilage adherence, or persistent mechanical symptoms. The cartilage replacement technique, particulated juvenile cartilage allograft transplantation (PJCAT), is a novel treatment option supported by the benefits of ease of application, no need for perpendicular access to the OLT, and the delivery of viable hyaline cartilage. However, there is minimal clinical data to support this treatment option. The purpose of this study was to determine the efficacy of PJCAT. Methods: After obtaining IRB approval, we conducted a retrospective review of patients that underwent PJCAT for the treatment of OLTs at a single academic institution. From 2012 to 2015, 18 patients were identified. However, one patient died of an unrelated cause and two patients were lost to follow-up leaving 15 patients (7 males and 8 females) whom had a minimum of 12 months of follow up (mean 34.6, range, 12-51 months). The mean age of this cohort was 32.7 years (15-48) at time of surgery with BMI average 29.9 (18.8-40.2). The primary outcome was failure of the procedure defined as: recurrent or worsening symptoms with corresponding imaging demonstrating delamination, and/or the need for a secondary cartilage restoration procedure. Variables studied included: size of lesion denoted by MRI, intraoperative size, etiology (traumatic versus atraumatic), location of lesion, sex, age, and history of prior surgery. Results: Failure of primary procedure as defined by continued pain with corresponding imaging and/or necessity of secondary cartilage procedure after use of PJCAT was 40% (6/15). Preoperative MRI size (188.7 +/- 81.7mm2 vs. 113.5 +/- 50.5mm2, p<0.05) was significant predictors of PJCAT failure. Furthermore, male sex was predictive of failure(p<0.05). Age, BMI, etiology, technique (open versus arthroscopic), history of prior surgery nor location were predictors of failure. Lastly, patients with lesions greater than 125mm2 area were at a statistically significant increased risk of clinical failure. Functional outcome scores were significantly better at final follow-up in the patients who had undergone successful treatment versus those who did not: AOFAS score (89.4 +/- 8.4 vs. 65.8 +/- 26.7) and FAOS total (77.9 +/- 13.2 vs. 47.9 +/- 24.8). Conclusion: These findings demonstrate the association of preoperative MRI lesion size, intraoperative lesion size and male sex as risk factors for failure of PJCAT setting of an already difficult to treat pathology.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

Proteomic Analysis of the Vitreous Body in Proliferative and Non-Proliferative Diabetic Retinopathy

2020 ◽  
Vol 17 ◽  
Author(s):  
Van-An Duong ◽  
Jeeyun Ahn ◽  
Na-Young Han ◽  
Jong-Moon Park ◽  
Jeong-Hun Mok ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Vitreous Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Protein Protein Interaction ◽  
Alpha Beta ◽  
New Treatment

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

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