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Euglycemic Dka Medscape

'understand This Warning': Sglt2s And Ketoacidosis

'understand This Warning': Sglt2s And Ketoacidosis

'Understand This Warning': SGLT2s and Ketoacidosis Recognition Key in Emergency Departments and Urgent Care Centers This feature requires the newest version of Flash. You can download it here . Hi. I'm Dr Anne Peters. Today I'm going to talk about the US Food and Drug Administration's (FDA) warning about the development of diabetic ketoacidosis (DKA) in individuals taking SGLT2 inhibitors.[ 1 ] The most important headline about this is that it can occur and it seems to be a rare occurrence, therefore people miss it. It's important that physicians in the emergency department and urgent care settings, as well as the rest of us, realize that a patient with either type 1 or type 2 diabetes who presents with anion gap metabolic acidosis can have ketoacidosis. Once that is recognized, the treatment becomes simple, which is intravenous insulin and glucose. However, many of these patients are euglycemic, so providers aren't tipped into thinking that it's ketoacidosis. They think it's something else. It is very important that we be aware that this can happen so that we can recognize it and treat it appropriately.[ 2 ] I also want to make it clear that I think SGLT2 inhibitors are great drugs for the treatment of type 2 diabetes and they should continue to be used, but people need to be aware that they can cause ketoacidosis. They are also used off label for the treatment of type 1 diabetes. Although I think that it's very effective in treating individuals with type 1 diabetes, it is currently not an FDA-approved use. Because of these concerns, I suggest not using this drug in patients with type 1 diabetes until we know more about this phenomenon. It turns out that I have seen a number of cases of ketoacidosis in my experience with using these drugs. Most of the cases I've seen Continue reading >>

Euglycaemic Ketoacidosis In A Non-diabetic Primigravida Following An Appendicectomy

Euglycaemic Ketoacidosis In A Non-diabetic Primigravida Following An Appendicectomy

Pregnancy creates significant alterations in energy metabolism which itself is a physiological adaptation to provide continuous flow of energy metabolites to the foetus. The state of insulin resistance created by hormonal changes in pregnancy enables free flow of glucose to the foetus and allows its absorption through facilitated diffusion. As glucose is preferentially available for the foetus, maternal fasting glucose level would be less than that of a non-pregnant state and in contrast plasma ketones and free fatty acids levels are elevated, resulting in a state of accelerated starvation. These metabolic alterations place a pregnant woman at a higher risk of developing euglycaemic ketoacidosis when allowed to fast for prolonged periods due to medical, surgical and psychological reasons. We report a rare case of euglycaemic ketoacidosis causing severe increased anion gap metabolic acidosis in a non-diabetic mother following surgery for appendicitis at a gestation of 27 weeks. Euglycaemic ketoacidosis is a condition characterized by accelerated ketogenesis in cellular level in spite of adequate supply of glucose for energy metabolism, in contrast to diabetic ketoacidosis where there is intracellular glucose depletion resulting in accelerated ketogenesis providing keto acids as an alternative energy metabolite. The hormonal changes that occur in pregnancy create a state of insulin resistance allowing free flow of glucose to the foetus. Thus, prolonged starvation in a pregnant woman will place her at high risk of starvation ketosis. We describe a 27-year-old non-diabetic primigravida woman who presented with increased anion gap metabolic acidosis secondary to starvation ketoacidosis following prolonged fasting and vomiting due to appendicitis. A 27-year-old primigravida w Continue reading >>

Sglt2 Inhibitor-linked Diabetic Ketoacidosis Is Rare, But Severe

Sglt2 Inhibitor-linked Diabetic Ketoacidosis Is Rare, But Severe

SGLT2 Inhibitor-Linked Diabetic Ketoacidosis Is Rare, but Severe Many cases of sodium-glucose cotransporter-2 (SGLT2) inhibitor-associated diabetic ketoacidosis (DKA) are preventable, new research suggests. But physicians and patients are missing the signs and symptoms of this rare side effect or not even aware of the link and as a result, any cases are severe and one was fatal, according to this latest audit of Australian databases, published online February 13 in Diabetes Care by Emily J Meyer, MBBS, of the Royal Adelaide Hospital and University of Adelaide, Australia, and colleagues. As DKA was initially missed by both patients and physicians, likely due in part to relative euglycemia, this led to delayed treatment, say the researchers. However, "identifiable precipitants were often present, suggesting the potential for risk mitigation," Meyer and colleagues write. Stop SGLT2 Inhibitors for Acute Illness, Surgery The US Food and Drug Administration (FDA) first warned about the risk for DKA with SGLT2 inhibitors, a relatively new class of oral agents for type 2 diabetes, in 2015, and the European Medicines Agency followed suit in 2016. The phenomenon has also been reported several times in the literature, including in the New England Journal of Medicine in 2017. The advice has been, and the Australian authors agree, that SGLT2 inhibitors should be temporarily stoppedduring acute illness or surgery. The possibility of DKA should be considered in any patient taking one of the agents who presents with malaise, nausea, and/or vomiting, they add. The drug should be stopped and, if caught early, the patient given hydration, carbohydrates, and insulin to prevent progression to DKA. Also, Meyers and colleagues suggest excluding a diagnosis of autoimmune diabetes (type 1 or l Continue reading >>

Diabetic Ketoacidosis In A Patient With Type 1 Diabetes On Sodium-glucose Co-transporter-2 Inhibitorsa Case Report

Diabetic Ketoacidosis In A Patient With Type 1 Diabetes On Sodium-glucose Co-transporter-2 Inhibitorsa Case Report

US Endocrinology,2017;13(2):724 DOI: We describe a case of a 26-year-old female with long-standing type 1 diabetes (T1D), on multiple subcutaneous insulin injections, who had been taking empagliflozin for the past year. She was detected to have severe diabetic ketoacidosis (DKA) with relatively lower blood glucose values during hospitalisation for dengue fever. The factors that precipitated the DKA are discussed, along with the unique challenges in the management of her metabolic status. While sodium-glucose co-transporter-2 (SGLT2) inhibitors have several potential benefits as adjunctive add-on therapy to insulin in T1D, the evidence is limited to short-term studies. However, their off-label use is increasing and there have been concerns related to increased risk of diabetic ketoacidosis. At present, SGLT2 inhibitors are not approved for use in T1D, and the risks should be discussed at length with the patient. Keywords: Type 1 diabetes, diabetic ketoacidosis, euglycaemic diabetic ketoacidosis, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin Disclosure: Gagan Priya and Vishal Bhambri have nothing to declare in relation to this article. No funding was received in the publication of this article Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: September 20, 2017 Published Online: October 17, 2017 Correspondence: Gagan Priya, Department of Endocrinology, Fortis Hospital, Phase 8, Mohali 160059, India. E: [email protected] We report a case of diabetic ketoacidosis in a 26-year-old female with long-standing type 1 diabetes (T1D) who was on mult Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Professor of Pediatric Endocrinology University of Khartoum, Sudan Introduction DKA is a serious acute complications of Diabetes Mellitus. It carries significant risk of death and/or morbidity especially with delayed treatment. The prognosis of DKA is worse in the extremes of age, with a mortality rates of 5-10%. With the new advances of therapy, DKA mortality decreases to > 2%. Before discovery and use of Insulin (1922) the mortality was 100%. Epidemiology DKA is reported in 2-5% of known type 1 diabetic patients in industrialized countries, while it occurs in 35-40% of such patients in Africa. DKA at the time of first diagnosis of diabetes mellitus is reported in only 2-3% in western Europe, but is seen in 95% of diabetic children in Sudan. Similar results were reported from other African countries . Consequences The latter observation is annoying because it implies the following: The late diagnosis of type 1 diabetes in many developing countries particularly in Africa. The late presentation of DKA, which is associated with risk of morbidity & mortality Death of young children with DKA undiagnosed or wrongly diagnosed as malaria or meningitis. Pathophysiology Secondary to insulin deficiency, and the action of counter-regulatory hormones, blood glucose increases leading to hyperglycemia and glucosuria. Glucosuria causes an osmotic diuresis, leading to water & Na loss. In the absence of insulin activity the body fails to utilize glucose as fuel and uses fats instead. This leads to ketosis. Pathophysiology/2 The excess of ketone bodies will cause metabolic acidosis, the later is also aggravated by Lactic acidosis caused by dehydration & poor tissue perfusion. Vomiting due to an ileus, plus increased insensible water losses due to tachypnea will worsen the state of dehydr Continue reading >>

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Sglt2 Inhibitors And Diabetic Ketoacidosis: What's All The Fuss About?

Sglt2 Inhibitors And Diabetic Ketoacidosis: What's All The Fuss About?

This activity is intended for emergency medicine physicians, diabetologists and endocrinologists, and primary care physicians. The goal of this activity is to explore the potential link between sodium-glucose cotransporter 2 (SGLT2) inhibitors and diabetic ketoacidosis and discuss best practices in diagnosis and management. Upon completion of this activity, participants will be able to: Interpret the evidence of how the mechanism of SGLT2 inhibitors relates to the development of DKA Describe the presentation, diagnosis, and management of euglycemic diabetic ketoacidosis As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest. Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content. Disclosure: Irl B. Hirsch, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Abbott Laboratories; Roche; Valeritas Received grants for clinical research from: Novo Nordisk; Sanofi Dr Hirsch does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States. Dr Hirsch does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States. Prof Continue reading >>

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Euglycemic Dka: It’s Not A Myth

Euglycemic Dka: It’s Not A Myth

Background: Diabetic ketoacidosis (DKA) is traditionally defined as a triad of hyperglycemia (>250mg/dL), anion gap acidosis, and increased plasma ketones. There is another entity that providers must be aware of known as euglycemic DKA (euDKA), which is essentially DKA without the hyperglycemia (Serum glucose <200 mg/dL). Euglycemic DKA is a rare entity that mostly occurs in patients with type 1 diabetes, but can possibly occur in type 2 diabetes as well. The exact mechanism of euDKA is not entirely known, but has been associated with partial treatment of diabetes, carbohydrate food restriction, alcohol intake, and inhibition of gluconeogenesis. euDKA, can also be associated with sodium-glucose cotransporter 2 (SGLT-2) inhibitor medications. These medications first came onto the market in 2013 and are FDA approved for the treatment of type 2 diabetes, however many physicians use them off-label for type I diabetes due to their ability to improve average glucose levels, reduce glycemic variability without increasing hypoglycemia, and finally promote weight loss. Does euDKA Exist even in Patients not Using SGLT-2 Inhibitors? The short answer is YES. Munro JF et al [5] reviewed a case series of 37 episodes of euDKA in a publication from 1973. Although, dated and not robust evidence some take home messages can be derived: All but one episode was in insulin dependent diabetics Vomiting was the most frequent symptom of euDKA in 32% of patients Management in most cases consisted of: Intravenous fluids and electrolyte replacement. No deaths occurred in this case series What are the Names of the SGLT-2 Inhibitors? Ipragliflozin (Suglat) – Approved in Japan Dapagliflozin (Farxiga) – 1st SGLT2 Inhibitor Approved; Approved in US Luseogliflozin (Lusefi) – Approved in Japan Tofo Continue reading >>

Starvation-induced True Diabetic Euglycemic Ketoacidosis In Severe Depression

Starvation-induced True Diabetic Euglycemic Ketoacidosis In Severe Depression

Go to: A 34-year-old man with a 19-year history of type 1 diabetes presented as an emergency with a 4-day history of nausea, vomiting, and flu-like symptoms. He was on a basal bolus insulin regime comprising 8 units of bolus insulin lispro injected at mealtimes and 12 units of basal isophane insulin at bedtime, but did not monitor capillary blood glucose levels. He did however empirically increase his insulin doses during times of illness and had increased his isophane insulin to 15 units during the 3 days prior to presentation. He had only one prior hospital admission, which occurred 6 years previously and was due to an episode of DKA precipitated by gastroenteritis. He was single, unemployed, did not drink alcohol, had no previous psychiatric history, no family history of diabetes or other medical conditions, and lived in a hostel. He had a record of poor clinic attendances and a history of long-term cannabis use. He denied any salicylate consumption, but admitted to some weight loss; however, he was unable to quantify this. His body mass index (BMI) was 19 kg/m2, and he looked unkempt. Physical examination revealed a temperature of 36.4°C (97.5°F), heart rate of 106 beats per minute, supine blood pressure of 131/85 mmHg, and sitting blood pressure of 122/80 mmHg. He had a respiratory rate of 30 breaths per minute, and his oxygen saturation using a pulsoximeter was 99% on room air. He appeared clinically dehydrated with dry oral mucosa, but cardiovascular, respiratory, abdominal, and neurological examinations were otherwise normal. Diabetic ketoacidosis (DKA) was suspected; metabolic acidosis was confirmed with a pH of 7.3, bicarbonate concentration of 10 mEq/l, and an elevated anion gap of 29 mEq/l [sodium = 134 mEq/l, potassium = 5.7 mEq/l, chloride = 101 mEq/l, b Continue reading >>

Euglycemic Diabetic Ketoacidosis, A Misleading Presentation Of Diabetic Ketoacidosis

Euglycemic Diabetic Ketoacidosis, A Misleading Presentation Of Diabetic Ketoacidosis

Go to: Introduction Hyperglycemia and ketosis in diabetic ketoacidosis (DKA) are the result of insulin deficiency and an increase in the counterregulatory hormones glucagon, catecholamines, cortisol, and growth hormone. Three processes are mainly responsible for hyperglycemia: increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilization by peripheral tissues. This might also be augmented by transient insulin resistance due to hormone imbalance, as well as elevated free fatty acids.[1] DKA is most commonly precipitated by infections. Other factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and illicit drug use. The diagnostic criteria of DKA, established by the American Diabetic Association, consists of a plasma glucose of >250 mg/dL, positive urinary or serum ketones, arterial pH of <7.3, serum bicarbonate <18 mEq/L, and a high anion gap. The key diagnostic feature of DKA is elevated circulating total blood ketone concentration. Hyperglycemia is also a key diagnostic criterion of DKA; however, a wide range of plasma glucose levels can be present on admission. Continue reading >>

Sglt2 Inhibitors And Diabetic Ketoacidosis: What's All The Fuss About? - #cme, #medscape #dka #euglycemia #euglycemic #diabetic #ketoacidosis, #sgl | Pinteres

Sglt2 Inhibitors And Diabetic Ketoacidosis: What's All The Fuss About? - #cme, #medscape #dka #euglycemia #euglycemic #diabetic #ketoacidosis, #sgl | Pinteres

Inhibitors and Diabetic Ketoacidosis: What's All the Fuss About? Methadone Maintenance Strategies to Improve Safe Prescribing. #CME #Medscape #Methadone #Medical #MedicalEducation #MedEd #ContinuingEducation #BrettSnodgrass #SnodgrassBrett #Methadone #Prescribing #Prescription #pharmacology Update on Clostridium difficile Infection. The Changing Landscape of Cystic Fibrosis: Clinical Updates From the 2015 European Cystic Fibrosis Society Meeting in Brussels - New Horizons in Cancer Immunotherapy: Management of Metastatic RCC - Diabetes and Dyslipidemia Novel Treatment Options for a Deadly Combination. Inhibitors in Type 2 Diabetes: Incorporating Current Data Into Practice - Getting Ahead of Metabolic and Mineral Disturbances in the Management of CKD-MBD: A Focus on Management Strategies - Quality in Diabetes Care: Achieving Quality Measures in My Practice - Preventing COPD Rehospitalizations Acute and Post acute Comprehensive Care to Enhance Quality and Improve Clinical Outcomes - #CME #COPD is third cause of death in USA and costs 50 billion dollars annually. Most of the costs are due to hospitalizations and inadequate prevention. NOACs for VTE Prophylaxis in Orthopedic Surgery:Balancing Safety and Efficacy - REMS for ER LA Opioid Analgesics: The Keys to Safe Use - #CME, #REMS, #Opioid, #PainMedicines, #PainMedicine, #Opiate, #Morphine, #Oxycontin, #Codeine, #Hydromorphone, #Fentanyl, #PPPA, #PPA, #Medscape Chronic Obstructive Pulmonary Disease Asthma or Both Differential Diagnosis and Comprehensive Management Strategies - #CME #BrettSnodgrass #Brett #Snodgrass "Brett Snodgrass MD" #COPD #Asthma #ACOS #LABA #SABA #ICS #IAMA #pulmonogy #primarycare #multispeciality Treating CTEPH When Are Surgical and Medical Options Appropriate - Clinical Perspectives on the Diagnosis Continue reading >>

Euglycemic Diabetic Ketoacidosis: A Potential Complication Of Treatment With Sodiumglucose Cotransporter 2 Inhibition

Euglycemic Diabetic Ketoacidosis: A Potential Complication Of Treatment With Sodiumglucose Cotransporter 2 Inhibition

Objective Sodiumglucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. Research Design and Methods Cases identified incidentally are described. Results We identified 13 episodes of SGLT-2 inhibitorassociated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. Conclusions SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes. Sodiumglucose cotransporter 2 (SGLT-2) inhibitors are the newest class of antihyperglycemic medications, first marketed in 2013 for the treatment of type 2 diabetes.[ 1 ] Limited studies suggest that SGLT-2 inhibitors may be effective in addressing many of the unmet needs of people with type 1 diabetes, including improving average glycemia, while reducing glycemic variability and postprandial hyperglycemia, without increasing hypoglycemia, as well as promoting weight loss while reducing insulin doses.[ 28 Continue reading >>

Type 1 And New Drug Jardiance

Type 1 And New Drug Jardiance

Furthermore, to add to my earlier comment about DKA, the term euglycemic DKA is the proper one. It is where (usually) type 1s exhibit all the symptoms of traditional DKA but without the uncontrolled BGs. This link details the patients who exhibited this that lead to the Invokana warnings: In everything Ive read, euglycemic DKA is far more prevalent in type 1s than type 2s. Reason being type 2s generally are producing enough insulin to keep keptones at bay, even when within normal diet-induced ketosis. Type 1s, of course, dont have that luxury. Heres another case study of euglycemic DKA: The bottom line is, ESPECIALLY for type 1s on this type of med, to closely monitor ketones. My rule of thumb to balance the risk with the rewards of Jardiance AND incorporating the lowest possible carb diet. is NEVER get above moderate ketones. Thats the danger zone. When I hit moderate, I immediately eat a fairly carby meal with my normal bolus. Ketones clear within 6-8 hours. Oh, and lots of water (which I do anyway living in Phoenix). Thanks @DanP , Ive been following all this in detail as well. The trouble we have is that the occurrence of euglycemic DKA is associated both with ketones being present as well as dehydration. There isnt really any evidence that ketones causes the DKA, just as their isnt any evidence that dehydration cases the DKA. In fact, a hypothesis that dehydration is a cause of DKA is much more likely given that dehydration is known to increase the risk of DKA and that SGTL2 drugs are also known to cause dehydration. A more detailed examination was a study done by Anne Peters and reported in Diabetes Care . This was a randomized controlled trial which found that SGT2s were associated with higher rates of DKA. The study reported that all serious events occurred in 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 >>

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