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Sglt2 Ketosis

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives

Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication. By blocking SGLT2 in the early proximal tubules of the kidney, these drugs decrease renal glucose retention, which is enhanced in hyperglycemia, thereby improving blood glucose control, in type 1 and type 2 diabetic patents. Their low hypoglycemia risk is due to the compensating reabsorption capacity of another glucose transporter, SGLT1, in the downstream late proximal tubule and the bodys metabolic counter-regulation, which remains intact during SGLT2 inhibition. When insulin dosage is lowered too much, SGLT2 inhibitors can enhance ketogenesis to the extent that the risk of diabetic ketoacidosis increases, particularly in type 1 diabetic patients. SGLT2 inhibitors improve the renal and cardiovascular outcome in type 2 diabetic patients. The mechanisms likely include a reduction in glomerular hyperfiltration, blood pressure, volume overload, and body weight, as well as lowering blood glucose without increasing the hypoglycemia risk. The same mechanistic effects are induced in type 1 diabetic patients. More studies are needed with SGLT2 inhibitors in type 1 diabetic patients, including renal and cardiovascular clinical outcome trials, to fully evaluate t Continue reading >>

Euglycemic Ketosis In An Adolescent With Type 1 Diabetes On Insulin And Dapaglifozin: Case Report

Euglycemic Ketosis In An Adolescent With Type 1 Diabetes On Insulin And Dapaglifozin: Case Report

Introduction: Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 inhibitor (SGLT2-I) induces glycosuria and reduces hyperglycemia in adults with type 2 diabetes. Objective:To present an euglycemic diabetic ketosis in an adolescent with type 1 diabetes (T1D) receiving dapagliflozin, to alert about the risk of a drug not approved in children nor in T1D. Case report: A 17 years old adolescent with T1D during 9 years, was started on dapagliflozin 10 mg/day to reduce insulin dose and weight. During 11 months on treatment, capillary ketones were undetectable and she exhibited a reduction in body mass index 23.9 to 21.1 kg/m2, basal insulin 40 to 17 U, glycated hemoglobin 8.3 to 7.5%, capillary glucose 175 to 161 mg/dl and glucose variability (standard deviation) 85 to 77. Suddenly nausea and vomits appeared. The patient was on an insulin pump and well calibrated continuous glucose monitoring, showing stable glucose levels under 200 mg/dl, and an insulin bolus was delivered. Vomiting without hyperglycemia persisted; three hours later, she was severely dehydrated and fainting, with ketones 4.6 nmol/l and glucose 224 mg/dl. She received IV saline fluids, ondansetron, carbohydrates and several insulin boluses. Hydration and general condition improved soon, however despite several insulin doses, ketosis continued for 24 hours. It is remarkable that the pump was working well and the cannula was not changed. After the ketosis was resolved, she continued using the same cannula with good metabolic control. Conclusion: Euglycemic ketosis is a life-threatening condition that must be suspected. Keywords: Ketosis; type 1 diabetes; dapagliflozin; SGLT2 inhibitor. Type 1 Diabetes (T1D) is difficult to manage in adolescents1. Sodium-glucose cotransporter type 2 inhibitors Continue reading >>

Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, And Preventable Safety Concern With Sglt2 Inhibitors

Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, And Preventable Safety Concern With Sglt2 Inhibitors

The Case At Hand Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System database. The scarce clinical data provided suggested that most of the DKA cases were reported in patients with type 2 diabetes (T2D), for whom this class of agents is indicated; most likely, however, they were insulin-treated patients, some with type 1 diabetes (T1D). The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. The following month, at the request of the European Commission, the European Medicines Agency (EMA) announced on 12 June 2015 that the Pharmacovigilance Risk Assessment Committee has started a review of all of the three approved SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to evaluate the risk of DKA in T2D (2). The EMA announcement claimed that as of May 2015 a total of 101 cases of DKA have been reported worldwide in EudraVigilance in T2D patients treated with SGLT2 inhibitors, with an estimated exposure over 0.5 million patient-years. No clinical details were provided except for the mention that “all cases were serious and some required hospitalisation. Although [DKA] is usually accompanied by high blood sugar levels, in a number of these reports blood sugar levels were only moderately increased” (2). Wit Continue reading >>

Prolonged Ketosis In A Patient With Euglycemic Diabetic Ketoacidosis Secondary To Dapagliflozin

Prolonged Ketosis In A Patient With Euglycemic Diabetic Ketoacidosis Secondary To Dapagliflozin

Sodium-glucose cotransporter 2 inhibitors (SGLT2) are the newest class of oral agents to receive US Food and Drug Administration (FDA) approval for the treatment of type 2 diabetes (T2DM). SGLT2 inhibitors currently approved by the FDA include canagliflozin, dapagliflozin, and empagliflozin as well as various combination drugs (Table 1). The enthusiasm this class of drugs has been greeted with stems from the benefits associated with SGLT2 inhibitors. They include decrease in A1c by 0.5% to 1%, reduction in insulin doses, modest weight loss, and improved systolic and diastolic blood pressure.1 In addition, the EMPA-REG OUTCOME trial showed a reduction in all-cause and cardiovascular mortality with empagliflozin.2 Also, a post hoc analysis of a study on dapagliflozin in type 2 diabetics with moderate renal impairment showed improved albuminuria and delayed progression to severe renal failure.3 The popularity of SGLT2 inhibitors is understandable considering the paucity of oral diabetic drugs that promote both weight loss and reduction of insulin needs. Endocrinologists and internists alike have increasingly prescribed this class of drugs as to avoid initiation of insulin or escalation of insulin doses. With more patients using SGLT2 inhibitors, reports of euglycemic diabetic ketoacidosis (euDKA) have emerged. While DKA can be expected with off-label use of SGLT2 inhibitors in patients with T1DM, it has also occurred in T2DM patients. Thus, the FDA posted a drug safety communication on DKA in 2015.4 Greater understanding of how to safely use this newest tool in our arsenal against diabetes is essential. A 50-year-old African American female with T2DM since the age of 35 presented with 10 days of constipation and fatigue, as well as reduced oral intake for 3 days prior to a Continue reading >>

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Get Unlimited Access On Medscape.

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Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives.

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives.

Abstract Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off-label use in patients with type 1 diabetes is diabetic ketoacidosis. The US Food and Drug Administration recently warned that SGLT2 inhibitors may result in euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 inhibitors may facilitate the development of ketosis or ketoacidosis. This provides the rationale for measures to lower the risk. We discuss the role of the kidney and potential links to renal gluconeogenesis and uric acid handling. Moreover, we outline potential beneficial effects of modestly elevated ketone body levels on organ function that may have therapeutic relevance for the observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system. KEYWORDS: diabetic ketoacidosis; ketogenesis; ketone body reabsorption; ketosis; kidney; sodium glucose cotransporter Continue reading >>

Sglt2 Inhibition And Ketoacidosis Should We Be Concerned? | Panicker Rajeev | British Journal Of Diabetes

Sglt2 Inhibition And Ketoacidosis Should We Be Concerned? | Panicker Rajeev | British Journal Of Diabetes

SGLT2 inhibition and ketoacidosis should we be concerned? Obesity and Endocrinology Research Group, Institute of Ageing and Chronic Disease, University of Liverpool Address for correspondence: Professor John PH Wilding Obesity and Endocrinology Research Group, University of Liverpool, Clinical Sciences Centre, Aintree University Hospital NHS Foundation Trust, SGLT2 inhibitors represent a novel class of oral glucose- lowering treatment that addresses some important unmet clinical needs in the treatment of type 2 diabetes, specifically weight reduction and a low propensity to cause hypoglycaemia. SGLT2 inhibition lowers the renal threshold for glucose excretion, resulting in renal glycosuria, a shift in substrate utilisation from carbohydrate to fat oxidation and hyperglucagonaemia; this poses a theoretical risk for ketoacidosis (including euglycaemic ketoacidosis) in the presence of other precipitating factors, especially reduction in insulin doses or low carbohydrate intake. There have been reports of several cases of ketoacidosis, mostly euglycaemic, and in people with type 1 or type 2 diabetes. Subsequent to this there were warnings from regulatory bodies (FDA and EMEA). In this article, we examine the reports of ketoacidosis associated with SGLT2 inhibition and try to explain the intrinsic pathophysiological mechanisms associated with this class of drugs which might contribute to ketoacidosis. The implications of these for clinical practice are summarised with key messages to health care providers. Key words: SGLT2 inhibitors, ketoacidosis, type 2 diabetes, mechanisms, clinical practice SGLT2 inhibitors are a new class of drugs for the treatment of type 2 diabetes that act by inhibiting renal glucose reabsorption. They have been adopted rapidly into clinical practic Continue reading >>

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives

Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, San Diego, CA, USA Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, San Diego, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, San Diego, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Volker Vallon, UC San Diego and VA San Diego Healthcare System, 3350 La Jolla Village Dr. (9151), San Diego, CA 92161, USA. Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, San Diego, CA, USA Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, San Diego, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, San Diego, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Volker Vallon, UC San Diego and VA San Diego Healthcare System, 3350 La Jolla Village Dr. (9151), San Diego, CA 92161, USA. Please review our Terms and Conditions of Use and check box below to share full-text version of article. I have read and accept the Wiley Online Library Terms and Conditions of Use. Use the link below to share a full-text ve Continue reading >>

Sglt2 Inhibitors May Predispose To Ketoacidosis

Sglt2 Inhibitors May Predispose To Ketoacidosis

SGLT2 Inhibitors May Predispose to Ketoacidosis Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Division of Diabetes, Endocrinology, and Nutrition (S.I.T.), Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201 Address all correspondence and requests for reprints to: Simeon I. Taylor, MD, PhD, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Mail Stop 1453, 9000 Rockville Pike, Bethesda, MD 20892. Search for other works by this author on: Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Search for other works by this author on: Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 28492852, Simeon I. Taylor, Jenny E. Blau, Kristina I. Rother; SGLT2 Inhibitors May Predispose to Ketoacidosis, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 28492852, Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of di Continue reading >>

Auctores | Article In Press | Review Article: Sglt2 Inhibitors And Ketoacidosis: Epidemiology And Pathophysiology

Auctores | Article In Press | Review Article: Sglt2 Inhibitors And Ketoacidosis: Epidemiology And Pathophysiology

Review Article: SGLT2 Inhibitors And Ketoacidosis: Epidemiology And Pathophysiology Review Article: SGLT2 Inhibitors And Ketoacidosis: Epidemiology And Pathophysiology Broadlawns Medical Center, Des Moines, University of Iowa. Corresponding author: Udaya M Kabadi, Broadlawns Medical Center, Des Moines, University of Iowa. E-mail: [email protected] , Phone: 3195948575 SGLT 2 inhibitors are a recent addition to the armamentarium of agents approved for treatment of hyperglycemia in management of type 2 diabetes. Unfortunately, the agents are fairly expensive with a modest efficacy rendering them to be probably the least cost effective drugs in management of hyperglycemia in subjects with type 2 diabetics. The cost efficacy falls even more because of additional expenses required for management of several short term and long term adverse outcomes causing a decline in quality of life. Ketosis and ketoacidosis are two of the several cautions issued by regulatory agencies and have gained prominence because of their serious nature with an occasional fatality. In this review, epidemiology and pathophysiology of onset of ketoacidosis in subjects administered SGLT2 inhibitors is discussed in order to improve recognition in early stage of the disorder and implement a prompt management strategy to prevent further morbidity, mortality as well as recurrent events. Corresponding author: Udaya M Kabadi, Broadlawns Medical Center, Des Moines, University of Iowa. E-mail: [email protected] , Phone: 3195948575 Received date: July 08, 2018; Accepted date; July 17, 2018; Published date: July 23, 2018. Copyright: 2018 Udaya M Kabadi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduc Continue reading >>

Euglycemic Ketosis In Patients With Type 2 Diabetes On Sglt2-inhibitor Therapyan Emerging Problem And Solutions Offered By Diabetes Technology

Euglycemic Ketosis In Patients With Type 2 Diabetes On Sglt2-inhibitor Therapyan Emerging Problem And Solutions Offered By Diabetes Technology

, Volume 56, Issue1 , pp 212216 | Cite as Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapyan emerging problem and solutions offered by diabetes technology Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials. However, sodium-glucose cotransporter2 inhibitors increase the risk of ketosis by increasing glucagon secretion in the pancreas and decreasing the renal excretion of 3-hydroxybutyrate and acetoacetate. When used in addition to insulin, any insulin dose reduction required to avoid hypoglycemia may lead to insufficient suppression of lipolysis and ketogenesis. sodium-glucose cotransporter2 inhibitor-induced loss of urinary glucose encourages euglycemia. Normo-glycemic or near-normoglycemic diabetic ketoacidosis represents a major threat to the health and well-being of a patient, because it may occur undetected and without any indicative hyperglycemia. In consequence, patients on sodium-glucose cotransporter2 inhibitors are recommended to perform regular blood ketone tests since they are not alerted to incipient diabetic ketoacidosis by glucose testing alone. This option is offered by several blood glucose meters that can also measure ketones with a separate ketone strip or in one case by an automatic par Continue reading >>

Euglycemic Ketosis In Patients With Type 2 Diabetes On Sglt2-inhibitor Therapy-anemerging Problem And Solutions Offered By Diabetes Technology.

Euglycemic Ketosis In Patients With Type 2 Diabetes On Sglt2-inhibitor Therapy-anemerging Problem And Solutions Offered By Diabetes Technology.

1. Endocrine. 2017 Apr;56(1):212-216. doi: 10.1007/s12020-017-1264-y. Epub 2017 Mar 17. Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy-anemerging problem and solutions offered by diabetes technology. Pftzner A(1), Klonoff D(2), Heinemann L(3), Ejskjaer N(4), Pickup J(5). (1)Pftzner Science & Health Institute, Mainz, UK. [email protected] (2)Mills Peninsula Healthcare Services, San Mateo, USA. (4)Department of Endocrinology, Clinical Institute, Aalborg University, Aalborg University Hospital, Aalborg, UK. (5)Division of Diabetes and Nutritional Sciences, King's College London, Guy's Hospital, London, UK. Diabetic ketoacidosis is an infrequent but life-threatening acute complication ofdiabetes, affecting predominantly patients with type 1 diabetes, children, andpregnant women, where ketosis is usually associated with marked hyperglycemia.Recently, an increasing number of cases have been reported of euglycemic diabeticketoacidosis in patients with type 2 diabetes receiving sodium-glucosecotransporter 2 inhibitor treatment in routine practice. There is a minor, butnot negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials. However, sodium-glucosecotransporter2 inhibitors increase the risk of ketosis by increasing glucagonsecretion in the pancreas and decreasing the renal excretion of 3-hydroxybutyrateand acetoacetate. When used in addition to insulin, any insulin dose reductionrequired to avoid hypoglycemia may lead to insufficient suppression of lipolysis and ketogenesis. sodium-glucose cotransporter2 inhibitor-induced loss of urinary glucose encourages euglycemia. Normo-glycemic or near-normoglycemic diabeticketoacidosis represents a major threat to the h Continue reading >>

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives.

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives.

Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives. @article{Qiu2017KetosisAD, title={Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives.}, author={Hongyu Qiu and Aleksandra Novikov and Volker Vallon}, journal={Diabetes/metabolism research and reviews}, year={2017}, volume={33 5}} Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off-label use inCONTINUE READING Endocrinology, diabetes & metabolism case reports Endocrinology, diabetes & metabolism case reports Mayoux E. CV protection in the EMPAREG OUTCOME trial: A "Thrifty Substrate" hypothesis Continue reading >>

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives

Ketosis And Diabetic Ketoacidosis In Response To Sglt2 Inhibitors: Basic Mechanisms And Therapeutic Perspectives

Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus Lowering Plasma Glucose Concentration by Inhibiting Renal SodiumGlucose CoTransport SGLT2 inhibitors in the treatment of type 2 diabetes Pharmacodynamics, efficacy and safety of sodiumglucose cotransporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus Renal hemodynamic effect of sodiumglucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus Sodiumglucose cotransporter 2 inhibition and glycemic control in type 1 diabetes: Results of an 8week openlabel proofofconcept trial SGLT2 inhibitors may predispose to ketoacidosis Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes Empagliflozin and progression of kidney disease in type 2 diabetes Physiological roles of ketone bodies as substrates and signals in mammalian tissues Fukao, T; Mitchell, G; Sass, JO; Hori, T; Orii, K; Aoyama, Y Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes A focused review of the role of ketone bodies in health and disease Transport of betahydroxybutyrate and acetoacetate along rat nephrons: a micropuncture study Ferrier, B; Martin, M; Janbon, B; Baverel, G Renal conservation of ketone bodies during starvation Renal reabsorption and utilization of hydroxybutyrate and acetoacetate in starved rats c/ebpdelta Null mouse as a model for the double knockout of slc5a8 and slc5a12 in kidney Cellular expression of a sodiumdependent monocarboxylate transporter (Slc5a8) and the MCT family in the mouse kidney Yanase, H; Takebe, K; NioKobayashi, J; TakahashiIwanaga, H; Iwanaga, T Expression of slc5a8 in kidney and its role in Na(+)coup Continue reading >>

Euglycemic Diabetic Ketoacidosis Sometimes Seen With Sglt2 Inhibitors

Euglycemic Diabetic Ketoacidosis Sometimes Seen With Sglt2 Inhibitors

Euglycemic Diabetic Ketoacidosis Sometimes Seen with SGLT2 Inhibitors Diabetic ketoacidosis (DKA) in patients with presenting serum blood glucose <200 mg/dL isnt common. More often, its seen in patients with type 1 diabetes in conjunction with starvation and acute illness.1 Its difficult to determine an incidence of euglycemic DKA (euDKA) among all DKA cases in the literature, given the migration of the serum glucose cutoff from 300 mg/dL to 200 mg/dL. The best estimation based on an analysis of case reports suggests an incidence anywhere between 0.8% and 7.5%.1 However, the sodium-glucose cotransporter-2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin can apparently induce this once-rare form of DKA.2,3 SGLT2 inhibitors are a class of oral hypoglycemic drugs indicated only for type 2 diabetes. Their novel mechanism of action prevents glucose reabsorption from the proximal renal tubules, resulting in increased glucosuria and decreasing plasma glucose. SGLT2 inhibitors lower serum glucose and HBA1C levels, and even produce weight loss. However, the increased glucose concentration in the bladder is a terrific incubation environment for fungi and bacteria, so much so that the FDA stuck a post-marketing warning on the drug class for the increased risk of serious urinary tract infections and urosepsis, in addition to euglycemic DKA. The proposed mechanism suggests that while SGLT2 inhibitors lower serum glucose, they also reduce insulin secretion from pancreatic beta cells in a negative feedback fashion. The lower serum insulin coupled with lower serum glucose consequently shifts energy metabolism to antilipolytic activity, and thus free fatty acid (FFA) oxidation and ketosis. Its been postulated that this SGLT2 inhibitor-induced insulin deficiency may pr Continue reading >>

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