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https://www.readbyqxmd.com/read/28086951/sodium-glucose-transporter-2-sglt2-inhibition-with-empagliflozin-improves-cardiac-diastolic-function-in-a-female-rodent-model-of-diabetes
#1
Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Brady Barron, Eric Mayoux, R Scott Rector, Adam Whaley-Connell, Vincent G DeMarco
Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28074254/the-cardiovascular-benefits-of-empagliflozin-sglt2-dependent-and-independent-effects
#2
EDITORIAL
Roberto Vettor, Silvio E Inzucchi, Paola Fioretto
No abstract text is available yet for this article.
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28063156/effect-of-a-selective-sglt2-inhibitor-luseogliflozin-on-circadian-rhythm-of-sympathetic-nervous-function-and-locomotor-activities-in-metabolic-syndrome-rats
#3
Asadur Rahman, Yoshihide Fujisawa, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
Metabolic syndrome is often associated with disruption of circadian rhythm of systemic hemodynamics and cardiovascular disease. Experiments were conducted to investigate the effects of luseogliflozin, a selective SGLT2 inhibitor, on circadian rhythm of sympathetic nervous function and locomotor activity (LA) in metabolic syndrome rats. The difference in the low frequency component of systolic blood pressure between the dark and light period significantly increased in the luseogliflozin-treated SHRcp. LA also increased in the dark period compared with the light period following luseogliflozin treatment...
January 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28052965/the-sglt2-inhibitor-dapagliflozin-prevents-cardiomyopathy-in-a-diabetic-lipodystrophic-mouse-model
#4
Michael Joubert, Benoît Jagu, David Montaigne, Xavier Marechal, Angela Tesse, Audrey Ayer, Lucile Dollet, Cédric Le May, Gilles Toumaniantz, Alain Manrique, Flavien Charpentier, Bart Staels, Jocelyne Magré, Bertand Cariou, Xavier Prieur
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into the mechanism driving the development of diabetic cardiomyopathy, we studied a unique model of T2DM: lipodystrophic Bscl2(-/-) (seipin knockout (SKO)) mice. Echocardiography and cardiac magnetic resonance imaging revealed hypertrophic cardiomyopathy with left ventricular dysfunction in SKO mice and these two abnormalities were strongly correlated with hyperglycemia...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28043708/emerging-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-cardiology
#5
REVIEW
Atsushi Tanaka, Koichi Node
The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting...
December 30, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#6
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27981497/factors-affecting-canagliflozin-induced-transient-urine-volume-increase-in-patients-with-type-2-diabetes-mellitus
#7
Hiroyuki Tanaka, Kazuhiko Takano, Hiroaki Iijima, Hajime Kubo, Nobuko Maruyama, Toshio Hashimoto, Kenji Arakawa, Masanori Togo, Nobuya Inagaki, Kohei Kaku
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. METHODS: Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days...
December 15, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27977934/longer-term-safety-and-tolerability-of-canagliflozin-in-patients-with-type-2-diabetes-a-pooled-analysis
#8
Rong Qiu, Dainius Balis, John Xie, Michael J Davies, Mehul Desai, Gary Meininger
OBJECTIVE: To evaluate the longer-term safety of canagliflozin, an SGLT2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: The safety/tolerability of canagliflozin 100 and 300mg were assessed using data pooled from 7 placebo- and active-controlled studies of 52-104 weeks in duration that enrolled a broad range of patients with T2DM (N = 5598). Canagliflozin 100 and 300mg as monotherapy or in combination with various background antihyperglycemic agents (AHAs) were compared with pooled non-canagliflozin treatments (ie, placebo, sitagliptin, glimepiride)...
December 15, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27941935/renal-metabolic-and-cardiovascular-considerations-of-sglt2-inhibition
#9
REVIEW
Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity...
January 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27928947/oral-glucose-lowering-drugs-and-cardiovascular-outcomes-from-the-negative-record-and-accord-to-neutral-tecos-and-promising-empa-reg
#10
C Tsioufis, E Andrikou, C Thomopoulos, N Papanas, D Tousoulis
Cardiovascular (CV) morbidity and mortality are higher among patients with diabetes mellitus type 2 (T2DM), particularly those with concomitant CV diseases, compared with other populations. In patients with T2DM, intensive glucose lowering reduces microvascular disease, but has a smaller and debated effect on CV events or mortality. In this setting, the US Food and Drug Administration (FDA) required in 2008 that all new agents for the treatment of T2DM should be evaluated in terms of CV safety. Metformin has long been established as first-line pharmacological therapy in patients with T2DM, due to its proven beneficial CV effects...
December 8, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27903028/-cardiovascular-morbidity-and-mortality-in-patients-with-kidney-disease
#11
Ivo Quack, Ralf Westenfeld
Patients with kidney disease have a significantly increased cardiovascular morbidity and mortality. Especially diabetics have an increased risk to develop renal insufficiency and cardiovascular events. Two recent studies show that the SGLT2 inhibitor Empagliflozin and the GLP1 agonist Liraglutid are able to lower the cardiovascular risk of type2 diabetics with renal insufficiency. Recent observations suggest that bradycardia and asystole are main triggers for sudden cardiac death in patients with chronic kidney disease...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27898586/an-update-on-sodium-glucose-co-transporter-2-inhibitors-for-the-treatment-of-diabetes-mellitus
#12
Daniel S Hsia, Owen Grove, William T Cefalu
PURPOSE OF REVIEW: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are the newest class of oral antihyperglycemic agents that have been approved for the treatment of diabetes mellitus. Over the past year, there have been significant developments in both the safety and efficacy of this class of medications that are presented in this review. RECENT FINDINGS: Apart from data on the glucose-lowering effect of SGLT2 inhibitors, other metabolic benefits have been demonstrated for this class of medications...
February 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27894216/bone-effects-of-canagliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-patients-with-type-2-diabetes-mellitus
#13
Thomas C Blevins, Azeez Farooki
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. It has been reported that SGLT2 inhibitors may have potential adverse effects on bone, including increased fracture risk and decreased bone mineral density (BMD). Across clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, vitamin D, or parathyroid hormone...
November 28, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#14
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27867961/cardio-renal-protection-with-empagliflozin
#15
Richard J MacIsaac, George Jerums, Elif I Ekinci
Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27866701/place-of-sodium-glucose-cotransporter-2-inhibitors-in-east-asian-subjects-with-type-2-diabetes-mellitus-insights-into-the-management-of-asian-phenotype
#16
REVIEW
Lee Ling Lim, Alexander Tong Boon Tan, Kevin Moses, Viraj Rajadhyaksha, Siew Pheng Chan
The burden of type 2 diabetes (T2DM) in East Asia is alarming. Rapid modernization and urbanization have led to major lifestyle changes and a tremendous increase in the prevalence of obesity, metabolic syndrome, and diabetes mellitus. The development of T2DM at a younger age, with lower body mass index, higher visceral adiposity, and more significant pancreatic beta-cell dysfunction compared to Caucasians are factors responsible for the increased prevalence of T2DM in East Asians. Sodium-glucose Cotransporter-2 (SGLT2) inhibitors (canagliflozin, dapaglifozin, empagliflozin, etc...
October 15, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27866224/the-beneficial-effects-of-empagliflozin-an-sglt2-inhibitor-on-atherosclerosis-in-apoe-mice-fed-a-western-diet
#17
Ji Hye Han, Tae Jung Oh, Ghayoung Lee, Hyo Jin Maeng, Dong Hwa Lee, Kyoung Min Kim, Sung Hee Choi, Hak Chul Jang, Hye Seung Lee, Kyong Soo Park, Young-Bum Kim, Soo Lim
AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE (-/-) mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27865185/a-new-era-in-the-management-of-type-2-diabetes-is-cardioprotection-at-long-last-a-reality
#18
EDITORIAL
Xavier Rossello, Derek M Yellon
The EMPA-REG OUTCOME and the LEADER trials have revealed a new era in the management of type 2 diabetes. The SGLT2 inhibitor empagliflozin demonstrated a lower rate of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke compared to placebo. Liraglutide, a GLP-1 analogue, succeeded to demonstrate reduction on a composite outcome including first occurrence of cardiovascular death, nonfatal myocardial infarction or non-fatal stroke. These two medications act through different mechanisms and has consequently shown different patterns of cardiovascular benefit...
February 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27829948/increased-hematocrit-during-sodium-glucose-cotransporter-2-inhibitor-therapy-indicates-recovery-of-tubulointerstitial-function-in-diabetic-kidneys
#19
REVIEW
Motoaki Sano, Makoto Takei, Yasuyuki Shiraishi, Yoshihiko Suzuki
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been attracting attention for cardiovascular as well as antidiabetic effects since the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME Trial) were reported. The hematocrit increases during treatment with SGLT2 inhibitors, which have a diuretic effect but do not cause sufficient hemoconcentration to increase the risk of cerebral infarction. Elevation of the hematocrit during SGLT2 inhibitor therapy is presumed to involve enhancement of erythropoiesis in addition to hemoconcentration...
December 2016: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/27819144/effects-of-sodium-glucose-co-transporter-2-inhibitors-on-metabolism-unanswered-questions-and-controversies
#20
Vasilios Tsimihodimos, Theodosios D Filippatos, Moses S Elisaf
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. These drugs also affect many anthropometric and metabolic parameters with various mechanisms of action. Areas covered: We present the available evidence regarding these effects. SGLT2 inhibitors can decrease body weight mainly due to a reduction of total fat mass. SGLT2 inhibitors can decrease blood pressure levels and serum uric acid levels and may also reduce the degree of diabetes-related albuminuria...
November 17, 2016: Expert Opinion on Drug Metabolism & Toxicology
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