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Sodium glucose transporters

Eisuke Kato
Plant materials have been widely studied for their preventive and therapeutic effects for type 2 diabetes mellitus (T2DM) and obesity. The effect of a plant material arises from its constituents, and the study of these bioactive compounds is important to achieve a deeper understanding of its effect at the molecular level. In particular, the study of the effects of such bioactive compounds on various biological processes, from digestion to cellular responses, is required to fully understand the overall effects of plant materials in these health contexts...
February 17, 2019: Bioscience, Biotechnology, and Biochemistry
Sung Eun Choi, Seth A Berkowitz, John S Yudkin, Huseyin Naci, Sanjay Basu
BACKGROUND: Personalizing medical treatment often requires practitioners to compare multiple treatment options, assess a patient's unique risk and benefit from each option, and elicit a patient's preferences around treatment. We integrated these 3 considerations into a decision-modeling framework for the selection of second-line glycemic therapy for type 2 diabetes. METHODS: Based on multicriteria decision analysis, we developed a unified treatment decision support tool accounting for 3 factors: patient preferences, disease outcomes, and medication efficacy and safety profiles...
February 15, 2019: Medical Decision Making: An International Journal of the Society for Medical Decision Making
Lindsey Burggraaff, Paul Oranje, Robin Gouka, Pieter van der Pijl, Marian Geldof, Herman W T van Vlijmen, Adriaan P IJzerman, Gerard J P van Westen
Sodium-dependent glucose co-transporter 1 (SGLT1) is a solute carrier responsible for active glucose absorption. SGLT1 is present in both the renal tubules and small intestine. In contrast, the closely related sodium-dependent glucose co-transporter 2 (SGLT2), a protein that is targeted in the treatment of diabetes type II, is only expressed in the renal tubules. Although dual inhibitors for both SGLT1 and SGLT2 have been developed, no drugs on the market are targeted at decreasing dietary glucose uptake by SGLT1 in the gastrointestinal tract...
February 14, 2019: Journal of Cheminformatics
Prakash Deedwania, Tushar Acharya
Diabetes mellitus is a major risk factor for cardiovascular (CV) disease. Conversely, CV disease is responsible for a majority of the deaths in patients with diabetes. Many drug trials have concentrated on blood glucose (hemoglobin A1c ) reduction. This strategy, while reducing microvascular outcomes like nephropathy and neuropathy, has little or no effect on reducing macrovascular events like heart attack, stroke, and heart failure. It has been postulated that hypoglycemia may counterbalance some of the beneficial effects of anti-hyperglycemic agents, but this is not proven...
February 15, 2019: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
A G Unnikrishnan, Sanjay Kalra, Vedavati Purandare, Hardik Vasnawala
Diabetes is a metabolic disorder characterized by hyperglycemia and is associated with several comorbidities and complications. Genital infection is one such complication that is often associated with diabetes mellitus (DM). Even though abnormalities in immune system, high urine glucose, and bladder dysfunction are important contributors for the increased risk of genitourinary symptoms, yet the possible role of pharmacologically induced glucosuria cannot be completely overlooked in such patients. There are various classes of medications to control blood glucose levels...
November 2018: Indian Journal of Endocrinology and Metabolism
Clifford J Bailey
Sodium/glucose co-transporter-2 (SGLT2) inhibitors, which lower blood glucose by increasing renal glucose elimination have been shown to reduce the risk of adverse cardiovascular (CV) and renal events in type 2 diabetes. This has been ascribed in part to haemodynamic changes, body weight reduction and several possible effects on myocardial, endothelial and tubulo-glomerular functions as well as reduced glucotoxicity. This review evaluates evidence that an effect of SGLT2 inhibitors to lower uric acid may also contribute to reduced cardio-renal risk...
February 14, 2019: Diabetes, Obesity & Metabolism
Athena Philis-Tsimikas, Liana K Billings, Robert Busch, Cristobal Morales Portillo, Rakesh Sahay, Natalie Halladin, Sarah Eggert, Kamilla Begtrup, Stewart Harris
AIMS: Progression of type 2 diabetes (T2D) necessitates intensification, often involving sequential combination of oral antidiabetic drugs (OADs) before initiation of insulin-based therapy. The DUAL IX trial ( NCT02773368) investigated the efficacy and safety of insulin degludec/liraglutide (IDegLira), vs insulin glargine 100 units/mL (IGlar U100), as add-on to sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy. MATERIALS AND METHODS: In this 26-week, Phase 3b, open-label, parallel-group, treat-to-target trial, conducted at 74 sites in 11 countries, insulin-naïve patients ≥18 years with HbA1c 7...
February 13, 2019: Diabetes, Obesity & Metabolism
Rishi Raj, Jon Hendrie, Aasems Jacob, Derick Adams
A 38-year-old female patient with well-controlled type 2 diabetes mellitus treated with canagliflozin underwent ureteral stent placement for obstructive renal calculi. Ten days following ureteroscopy and ureteral stenting, she developed fevers and blood cultures grew Candida glabrata ( C. glabrata ). The patient was successfully treated with an extended course of broad-spectrum antibiotics and antifungal agents. The clinical presentation of candidemia is indistinguishable from bacteremia resulting in delay in diagnosis and treatment...
2019: Frontiers in Endocrinology
Yunwen Xu, Scott J Pilla, G Caleb Alexander, Irene B Murimi
BACKGROUND: Clinical guidelines recommend that metformin be continued after insulin is initiated among patients with type 2 diabetes, yet little is known regarding how often metformin or other non-insulin diabetes medications are continued in this setting. METHODS: We conducted a retrospective cohort study to characterize rates and use patterns of six classes of non-insulin diabetes medications: biguanides (metformin), sulfonylureas, thiazolidinediones (TZDs), glucagon-like peptide 1 receptor agonists (GLP1 receptor agonists), dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors), and sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), among patients with type 2 diabetes initiating insulin...
2019: PloS One
Riobaldo Cintra, Filipe A Moura, Luis Sergio F de Carvalho, Joaquim Barreto, Marcos Tambascia, Roberto Pecoits-Filho, Andrei C Sposito
The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity...
January 2019: Revista da Associação Médica Brasileira
Thiago Quinaglia, Daniela C Oliveira, José Roberto Matos-Souza, Andrei C Sposito
Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM...
January 2019: Revista da Associação Médica Brasileira
Theodosios D Filippatos, Angelos Liontos, Ioanna Papakitsou, Moses S Elisaf
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. Two trials have shown significant reductions of cardiovascular (CV) events with empagliflozin and canagliflozin, which could not be attributed solely to their antidiabetic effects. Aim of the review is the critical presentation of suggested mechanisms/hypotheses for the SGLT2 inhibitors-cardioprotection. The search of the literature revealed many possible cardioprotective mechanisms, because SGLT2 inhibitors i) increase natriuresis and act as diuretics with unique properties leading to a reduction in preload and myocardial stretch (the diuretic hypothesis); ii) decrease blood pressure and afterload (the blood pressure lowering hypothesis), iii) favor the production of ketones, which can act as a "superfuel" in the cardiac and renal tissue (the "thrifty substrate" hypothesis), iv) improve many metabolic variables (the metabolic effects hypothesis), v) exert many anti-inflammatory effects (the anti-inflammatory effects hypothesis), vi) can act through the angiotensin II type II receptors in the context of simultaneous renin-angiotensin-aldosterone-system (RAAS) blockade leading to vasodilation and positive inotropic effects (the RAAS hypothesis), vii) directly decrease the activity of the upregulated in heart failure Na+ -H+ exchanger in myocardial cells leading to restoration of mitochondrial calcium handling in cardiomyocytes (the sodium hypothesis)...
February 13, 2019: Postgraduate Medicine
Pantelis Sarafidis, Charles J Ferro, Enrique Morales, Alberto Ortiz, Jolanta Malyszko, Radovan Hojs, Khaled Khazim, Robert Ekart, Jose Valdivielso, Denis Fouque, Gérard M London, Ziad Massy, Petro Ruggenenti, Esteban Porrini, Andrej Wiecek, Carmine Zoccali, Francesca Mallamaci, Mads Hornum
Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium-glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction...
February 1, 2019: Nephrology, Dialysis, Transplantation
Hillel Sternlicht, George L Bakris
PURPOSE OF REVIEW: This is an update of data regarding changes in blood pressure using sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of diabetes. The mechanism of blood pressure lowering by SGLT2i was thought to be due to their osmotic diuretic effects. New data, however, has emerged from meta-analyses and studies of people with impaired kidney function demonstrating similar or greater magnitudes of blood pressure reduction in the absence of significant glycosuria...
February 12, 2019: Current Hypertension Reports
Hanae Naceiri Mrabti, Moulay El Abbes Faouzi, François Massako Mayuk, Hanane Makrane, Nicolas Limas-Nzouzi, Siegfried Didier Dibong, Yahia Cherrah, Ferdinand Kouoh Elombo, Bernard Gressier, Jehan-François Desjeux, Bruno Eto
ETHNOPHARMACOLOGICAL RELEVANCE: Arbutus unedo L., (Ericaceae) is one of the most traditional plants commonly used to treat diabetes in people living in Eastern Morocco region particularly in Taza and Beni Mellal. AIM OF THE STUDY: The aim of the study was to find if there is a scientific support to the ethnopharmacological relevance use of Arbutus unedo L., roots bark (AU) to treat diabetes. MATERIALS AND METHODS: We studied the effects of crude aqueous extract of AU on intestinal glucose absorption using short-circuit current technique in vitro and oral glucose tolerance test in vivo...
February 8, 2019: Journal of Ethnopharmacology
Shazia Hussain, Tahseen A Chowdhury
Diabetes mellitus affects over 20% of people aged > 65 years. With the population of older people living with diabetes growing, the condition may be only one of a number of significant comorbidities that increases the complexity of their care, reduces functional status and inhibits their ability to self-care. Coexisting comorbidities may compete for the attention of the patient and their healthcare team, and therapies to manage comorbidities may adversely affect a person's diabetes. The presence of renal or liver disease reduces the types of antihyperglycemic therapies available for use...
February 11, 2019: Drugs
Ghulam Abbas, Ahmed Al Harrasi, Hidayat Hussain, Ahmed Hamaed, Claudiu T Supuran
Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Therefore, newer approaches and targets for the management of diabetes mellitus are highly desirable...
February 4, 2019: Bioorganic Chemistry
Pieter Martens, Joyce Janssens, Jobbe Ramaekers, Matthias Dupont, Wilfried Mullens
BACKGROUND: The choice of glucose lowering agent in heart failure (HF)-patients can have a strong effect on HF-related adverse events, with some classes increasing and other classes reducing the risk. Little data is available about the choice of glucose lowering agents in HF-patients with type-2-diabetes. METHODS: We performed a cross-sectional single centre point analysis of all patients with both a diagnoses of HF and type-2-diabetes followed in a tertiary HF-clinic...
February 8, 2019: Acta Cardiologica
Juan Pablo Frias
Combining antihyperglycemic agents in order to rapidly and safely achieve the best possible glycemic control is the standard of care today for the management of type 2 diabetes. Agents should ideally have mechanisms of actions that are complementary and that improve glycemic control without unacceptable gain in body weight or hypoglycemia. Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin...
February 5, 2019: Expert Review of Endocrinology & Metabolism
Y L He, W Haynes, C D Meyers, A Amer, Y Zhang, P Chen, A E Mendonza, S Ma, W Chutkow, E Bachman
BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with T2DM and/or obesity. METHODS: Patients with obesity (BMI 35-50kg/m2 ) were enrolled into a 12-week study (N=88; licogliflozin 150 mg q.d.). Patients with type-2 diabetes-mellitus (T2DM) were enrolled into a second, two-part study, comprising a single-dose cross-over (N=12; 2...
February 5, 2019: Diabetes, Obesity & Metabolism
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