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      Prolonged acidosis is a feature of SGLT2i-induced euglycaemic diabetic ketoacidosis

      research-article
      1 , 2 , 1 , 1 , 1 , 1 , 1 , 1 , 2
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd
      Adult, Female, Male, White, Ireland, Adrenal, Kidney, Diabetes, Insulin, Diabetes mellitus type 2, Diabetic ketoacidosis, Euglycemic diabetic ketoacidosis*, Metabolic acidosis, Diabetic ketoacidosis, Diabetes mellitus type 2, Euglycemic diabetic ketoacidosis*, Ketonuria, Metabolic acidosis, Nausea, Fatigue, Myasthaenia, Anorexia, Tachycardia, Tachypnoea, Dehydration, Glucosuria, Dry mucous membranes*, Acanthosis nigricans, Acrochorda, Syncope, Hypoglycaemia, Haemoglobin A1c, Glucose (blood), Urinalysis, Bicarbonate, pH (blood), Ketones (urine), Ketones (plasma), Lactate, Anion gap, BMI, Creatinine (serum), Estimated glomerular filtration rate, Electrolytes, Fluid repletion, SGLT2 inhibitors, Glucose, Atorvastatin, Canagliflozin, Dulaglutide*, Ezetimibe, Empagliflozin, Insulin glargine, Duloxetine*, Lercanidipine*, Doxazosin, Ramipril, Alpha-blockers, Pregabalin*, Insulin Aspart, Gliclazide, Sitagliptin, Cardiology, Nephrology, Surgery, Unusual effects of medical treatment, September, 2019

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          Summary

          We describe two cases of SGLT2i-induced euglycaemic diabetic ketoacidosis, which took longer than we anticipated to treat despite initiation of our DKA protocol. Both patients had an unequivocal diagnosis of type 2 diabetes, had poor glycaemic control with a history of metformin intolerance and presented with relatively vague symptoms post-operatively. Neither patient had stopped their SGLT2i pre-operatively, but ought to have by current treatment guidelines.

          Learning points:
          • SGLT2i-induced EDKA is a more protracted and prolonged metabolic derangement and takes approximately twice as long to treat as hyperglycaemic ketoacidosis.

          • Surgical patients ought to stop SGLT2i medications routinely pre-operatively and only resume them after they have made a full recovery from the operation.

          • While the mechanistic basis for EDKA remains unclear, our observation of marked ketonuria in both patients suggests that impaired ketone excretion may not be the predominant metabolic lesion in every case.

          • Measurement of insulin, C-Peptide, blood and urine ketones as well as glucagon and renal function at the time of initial presentation with EDKA may help to establish why this problem occurs in specific patients.

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          Most cited references7

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          Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials

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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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              AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THE ASSOCIATION OF SGLT-2 INHIBITORS AND DIABETIC KETOACIDOSIS.

              AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology DKA = diabetic ketoacidosis EMA = European Medicines Agency FDA = U.S. Food and Drug Administration SGLT-2 = sodium glucosecotransporter 2 T1D = type 1 diabetes T2D = type 2 diabetes.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                06 September 2019
                2019
                : 2019
                : 19-0087
                Affiliations
                [1 ]Galway University Hospitals , Galway, Ireland
                [2 ]HRB Clinical Research Facility , National University of Ireland Galway, Galway, Ireland
                Author notes
                Correspondence should be addressed to F M Finucane; Email: francis.finucane@ 123456hse.ie
                Article
                EDM190087
                10.1530/EDM-19-0087
                6765316
                31600728
                2f554105-08f9-42d4-b08e-3d0420e66bea
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 29 August 2019
                : 06 September 2019
                Categories
                Adult
                Female
                Male
                White
                Ireland
                Adrenal
                Kidney
                Diabetes
                Insulin
                Diabetes Mellitus Type 2
                Diabetic Ketoacidosis
                Euglycemic Diabetic Ketoacidosis*
                Metabolic Acidosis
                Diabetic ketoacidosis
                Diabetes mellitus type 2
                Euglycemic diabetic ketoacidosis*
                Ketonuria
                Metabolic acidosis
                Nausea
                Fatigue
                Myasthaenia
                Anorexia
                Tachycardia
                Tachypnoea
                Dehydration
                Glucosuria
                Dry mucous membranes*
                Acanthosis nigricans
                Acrochorda
                Syncope
                Hypoglycaemia
                Haemoglobin A1c
                Glucose (blood)
                Urinalysis
                Bicarbonate
                pH (blood)
                Ketones (urine)
                Ketones (plasma)
                Lactate
                Anion gap
                BMI
                Creatinine (serum)
                Estimated glomerular filtration rate
                Electrolytes
                Fluid repletion
                SGLT2 inhibitors
                Glucose
                Atorvastatin
                Canagliflozin
                Dulaglutide*
                Ezetimibe
                Empagliflozin
                Insulin glargine
                Duloxetine*
                Lercanidipine*
                Doxazosin
                Ramipril
                Alpha-blockers
                Pregabalin*
                Insulin Aspart
                Gliclazide
                Sitagliptin
                Cardiology
                Nephrology
                Surgery
                Unusual Effects of Medical Treatment
                Unusual Effects of Medical Treatment

                adult,female,male,white,ireland,adrenal,kidney,diabetes,insulin,diabetes mellitus type 2,diabetic ketoacidosis,euglycemic diabetic ketoacidosis*,metabolic acidosis,ketonuria,nausea,fatigue,myasthaenia,anorexia,tachycardia,tachypnoea,dehydration,glucosuria,dry mucous membranes*,acanthosis nigricans,acrochorda,syncope,hypoglycaemia,haemoglobin a1c,glucose (blood),urinalysis,bicarbonate,ph (blood),ketones (urine),ketones (plasma),lactate,anion gap,bmi,creatinine (serum),estimated glomerular filtration rate,electrolytes,fluid repletion,sglt2 inhibitors,glucose,atorvastatin,canagliflozin,dulaglutide*,ezetimibe,empagliflozin,insulin glargine,duloxetine*,lercanidipine*,doxazosin,ramipril,alpha-blockers,pregabalin*,insulin aspart,gliclazide,sitagliptin,cardiology,nephrology,surgery,unusual effects of medical treatment,september,2019

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