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      Newer Perspectives of Mechanisms for Euglycemic Diabetic Ketoacidosis

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      , ,
      International Journal of Endocrinology
      Hindawi

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          Abstract

          Euglycemic diabetic ketoacidosis (EDKA) was considered a rare condition with its specific definition and precipitating factors. However, with the wide use of sodium glucose cotransporter 2 (SGLT-2) inhibitors, the newest class of antidiabetic agents, EDKA has come back into the spotlight. Relevant cases are increasingly being reported along with insights into the mechanism of EDKA. It seems increasingly clear that EDKA is more common than we used to believe. The SGLT-2 inhibitor-associated EDKA also indicates a necessary review of our previous understanding of “diabetic” ketoacidosis, since the SGLT-2 inhibitor predisposes patients to DKA in a “starvation” way. Actually, there are growing reports about starvation-induced ketoacidosis as well. The previously “exclusive” nomenclature and cognition of these entities need to be reexamined. That the hormonal interactions in DKA may differ from the severity of insulin deficiency also may have served in the scenario of EDKA. The SGLT-2 inhibitors are newly approved in China. The main purpose of this work is to have a better understanding of the situation and update our knowledge with a focus on the pathogenesis of EDKA.

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          Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

          OBJECTIVE Sodium–glucose 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 inhibitor–associated 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.
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            Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors.

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              SGLT2 Inhibitors May Predispose to Ketoacidosis.

              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 diabetic ketoacidosis. In May 2015, the Food and Drug Administration issued a warning that SGLT2 inhibitors may lead to ketoacidosis.
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                Author and article information

                Contributors
                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi
                1687-8337
                1687-8345
                2018
                2 October 2018
                : 2018
                : 7074868
                Affiliations
                Department of Endocrinology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China
                Author notes

                Academic Editor: Henrik Falhammar

                Author information
                http://orcid.org/0000-0002-1812-9174
                http://orcid.org/0000-0002-4151-2411
                Article
                10.1155/2018/7074868
                6189664
                30369948
                355cc4ac-1e4d-4e90-8247-6f3f7130076a
                Copyright © 2018 Xiaofang Yu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 February 2018
                : 18 July 2018
                : 9 September 2018
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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