Magbri A, El-Magbri E, El-Magbri M, Brar B, Rashid S. J Cardiol and Cardiovasc Sciences (2017) 1(1): 21-23

Case Report Open Access

High Anion Gap Metabolic Acidosis due to Euglycemic Diabetic Keto- acidosis Caused by Sodium-Glucose Co-transporter 2 inhibitor Awad Magbri, Eusera El-Magbri, Mariam El-Magbri, Brar Balhinder and Shauket Rashid Toledo Vascular Access Clinic, Toledo, OH, USA

Article Info Case history

Article Notes The case is that of 58 year-male with type 2 diabetes mellitus Received: December 05, 2017 for 7 years, hypertension, hypercholesterolemia, who was admitted Accepted: December 26, 2017 to the hospital with left lower limb cellulitis over the past 8 days. *Correspondence: On work-up he was found to have high anion-gap metabolic acidosis Dr. Awad Magbri, Toledo Vascular Access Clinic, Toledo, OH, (AGMA) with anion gap of 25, his lactate levels were normal (D USA; Email: [email protected] and L-lactate). He denies overdosing with any medications and his © 2017 Magbri A. This article is distributed under the terms of toxicology screen for methanol, ethanol, aspirin, and ethylene glycol the Creative Commons Attribution 4.0 International License. were negative. He has no psychiatric history of note. He denies using Keywords over the counter medications like acetaminophen. No bowel surgery Diabetes mellitus could be elicited. He felt dehydrated and nauseous but otherwise Diabetic ketoacidosis Euglycemic diabetic ketoacidosis Sodium-glucose cotransporter 2 inhibitor fine.His medications includes; carvedalol 25mg twice daily, Metabolic acidosis hydrochlothiazide 25 mg daily, Lipitor 20 mg daily, insulin, aspirin High anion gap acidosis

ago to control his blood sugar level and A1C. 81 mg daily, and was started on canagliflozoin 300 mg daily 4 weeks Physical examination of the patient revealed, slightly dehydrated but well-nourished man, his vital signs; heart rate of 78 BPM and

heart,regular, abdomen, BP 143/85 and chest mmHg, were temperature unremarkable. 98.7 He F, had and left his lower oxygen leg cellulitissaturation but while no edema breathing or tenderness. room air was 92%. Examination of the His work-up including chemistry-7 which showed sodium of

142 mmol/L, potassium of 4.3 mmol/L, chloride of 102 mmol/L, bicarbonate of 13 mmol/L, BUN and creatinine of 18 mg/L and 0.78 pHmg/L was respectively. 7.2 with a Hiscarbon blood dioxide glucose in level blood was gas 178 analysis mg/L (Pco2)with A1C of of 8.2. His serum osmolality was 312 mosm/L, and his arterial blood level. His investigation also showed positive ketones in the serum and32mmHg. urine. His His calculated urine PH anionwas 5.5 gap and was the 25 urine given containhis normal >800 albumin mg of glucose. Case discussion

of theMetabolic serious and acidosis acute complications is defined as of low diabetes. pH <7.3It is characterized with serum bybicarbonate increased level total of <22body mmol/L. ketone Diabetic levels, ketoacidosismetabolic acidosis, (DKA) is andone hyperglycemia. Hyperglycemia is a key component for the diagnosis

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of DKA. There is another DKA with normal blood glucose Treatment1. of DKA and eDKA are the same and includes; described first by Munro in 1 1973; where he reported cardiac function, renal function, and mental status glucose in 17 young patients . Later on normoglycemia volume resuscitation, frequent assessment of 37 episodes of DKA with normal or near normal blood 16 2 edema have and avoidance of fluid overload and pulmonary demonstratedis defined as blood that fastingsugar <250mg/L.in type 1 diabetic It is now patients known can as 2. Low dose intra-venous regular insulin. leadEuglycemic to blunted diabetic hyperglycemic ketoacidosis response (eDKA). which Burge can et al lead to 3. Correction of potassium abnormality . 4. eDKA. These researchers demonstrated3 that dehydration can enhance the development of eDKA Resolution of DKA can be assessed by the presence can be distinguished from other causes of ketoacidosis by of 2 of the following: an anion gap <12,4,17 serum Euglycemic DKA is part of the spectrum of DKA and clinical history and serum bicarbonate levels. The level bicarbonate level >15, or a venous pH >7.3 of bicarbonate in starvation ketosis is usually normally patient and the health care individual that normal blood sugarThe resulted important in the features de-escalation in eDKA isof the the perception insulin dose by and the anion gap metabolic acidosis like lactic acidosis, drug intoxications,more than 18 andmEq/L. renal The failure absence as well of other as the causes presence of high of perpetuation of the eDKA. sugars is critical and blood gas analysis for AGMA as other causes of AGMA . Many workers demonstrated wellAwareness as estimation that of DKA serum can and occur urine without ketones high are blood keys ketones in the plasma and4 urine distinguish eDKA from 5 Mellitus management of the condition. arethat infections eDKA can6-8 occur in both type 1 and type 2 diabetes for the correct diagnosis of eDKA and hence, successful myocardial. The infarction, most common and illicit causes drug that use 8-10precipitated. The American DKA In conclusion: all patients with type-1 or 2 diabetes , inadequate insulin therapy, pancreatitis, on SGLT-2 inhibitors with nausea, vomiting, shortness of breath, or malaise should have chemistry-7, blood gas Diabetic Association, defined DKA as plasma glucose of analysis, and urine and serum ketones estimation to avert >250 mg/L, positive urinary or serum ketones, arterial PH of <7.3,The serumcase under bicarbonate discussion <18 mEq/L, satisfy andall highthe criteriaanion gap. of Referencesthe complications of eDKA. 1. transporterDKA except 2 hyperglycemia. inhibitor (SGLT-2 In inhibitors) 2013, the for food management and drug administration (FDA) approved many sodium-glucose co- Munro JF, Campbell IW, McCuish AC, et al. Euglycemic diabetic of type -2 diabetes mellitus. The use of these drugs in 2. ketoacidosis. BMJ. 1973; 2: 578-80. type-1 and 2-DM have increased the side effects and the Burge MR, Hardy KJ, Schade DS. Short-term fasting is a mechanism for . The adverse effects the development of Euglycemic ketoacidosis during periods of insulin 11-13 deficiency.Burge MR, JGarcia Clin Endocrinol N, Quall CR, Metab. et al. 1993; Deferential 76: 1192-98. effects of fasting and risks of eDKA in these patients dehydration in the pathogenesis of diabetic ketoacidosis. Metabolism. 3. of these drugs were recorded in 73 cases linked to eDKA. 2001; 50: 171-77. haveAll patients diabetes required type-2. SGLT-2 hospitalization inhibitors and in these their patients average blood glucose level was 211mg/L. 60% of these patients 4. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in The majority of the cases had infection, dehydration, and 5. adult patients with diabetes. Diabetic Care. 2009; 32: 1335-43. de-escalationwere started onof insulinaverage doses. of 45 daysThe managementprior to the incident.of these Rawla P, Vellipuram AP, Bandaru SS, et al. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma. Endo. Diab & 6. National center for health statistics. National hospital discharge and with rehydration, insulin supplementation and treatment Metabol. 2017; 1-4. http://www.edmcasereports.com ofpatients the underlying were in the precipitating same line as patientscause. In with some classic of these DKA ambulatory surgery data (article online) available from http://www. patients re-challenged with SGLT-2 inhibitors resulted in 7. cdc.gov/nchs/about/major/hdasd/nhds.htm. 11. hyperglycemic crises in patients with diabetes. Diabetic care. 2001; Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of Restriction of carbohydrate usage because of infection the development of eDKA 8. or dehydration along with de-escalation of the insulin 24: 131-153 doses because of normal blood sugars, and excretion of Ennis ED, Stahl EJVB, Kreisberg RA. The hyperosmolar hyperglycemic large amount of blood glucose in the urine as part of the syndrome. Diabetes Rev. 1994; 2: 115-26. effect of SGLT-2 inhibitors are suggested as the basis of the 9. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises 10. in adult patients with diabetes. Diabetes Care. 2006; 29: 2739-2748 the fat oxidation for energy with ensuing ketoacidosis . Defronzo RA, Matzuda M, Barret E. Diabetic ketoacidosis: a combined pathogenesis of eDKA. These factors increased reliance14,15 on metabolic-nephrologic approach to therapy. Diabetes Rev. 1994; 2: 209-238

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11. A potential complication of treatment with sodium-glucose co- glucose cotransporter 2 inhibitor in a diabetic patient with low Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: 14. Hayami T, Kato Y, Kamiya H, et al. Case of ketoacidosis by a sodium-

12. transporter 2 inhibition. Diabetic Care. 2015; 38(9): 1687-93. 15. carbohydrateSt Hilaire R, Costello diet. J Diabetes H. Prescriber Invest. beware: 2015; 10: report 12330 of adverse effects sodium-glucose co-transporter 2 inhibitor, as add-on to insulin in of sodium-glucose cotransporter 2 inhibitor use in a patient with Henry, Robert R, et al. “Efficacy and safety of the canagliflozoin, a

patients with type 1 diabetes.” Diabetes care. 2015; 38(12): 2258-2267. 16. contraindication. Am J Emerg Med 2015; 33: 604. E3-e4. preventable safety concern with SGLT 2 inhibitor.” Diabetes Care. Societies. Joint British Diabetes Societies guideline for the 13. “Euglycemic diabetic ketoacidosis: a predictable, detectable, and managementSavage MW, Dhatariyaof diabetic KK,ketoacidosis. Kilvert A, Diabet et al. Med. Joint 2011; British 28: Diabetes508-15.

may2015(39.9): result in1638-42. a serious US conditionFood and ofDrug too Administration. much acid in the“FDA blood.” Drug 17. Safety Communication: FDA warns that SGLT 2 inhibitors for diabetes Jenkins D, Close CF, Krentz AJ, et al. Euglycemic diabetic ketoacidosis: Bethesda. MD: Food and Drug Administration. 2015 May 15 (2015). Does it exist. Acta Diabetol. 1993; 30: 251-53.

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