CONSIDERATIONS FOR SODIUM-GLUCOSE TRANSPORTER 2 INHIBITOR THERAPY RESULTING IN EUGLYCEMIC DIABETIC KETOACIDOSIS

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sodium-glucose transporter 2 inhibitors (SGLT2i) have recently become an increasingly popular treatment choice for type 2 diabetics. A rare complication of SGLT2i use is euglycemic diabetic ketoacidosis (EDKA), during which life threatening severe metabolic acidosis and ketonemia arises in the setting of glucose levels of <250 mg/dL. CASE PRESENTATION: A 40-year-old male with a history of presumed type 2 diabetes mellitus (DM-2) which was diagnosed six years prior was transferred to our intensive care unit with persistent diabetic ketoacidosis (DKA). Past medical history was positive for prior episodes of DKA. His diabetic medications included glimepiride, dapagliflozin, metformin, and degludec insulin. He presented with a one day history of vomiting and polydipsia. Despite five liters of intravenous (IV) fluids, IV bicarbonate, and IV insulin, he persisted with a high anion gap metabolic acidosis (HAGMA). Lab work revealed an anion gap of 32, an osmolar gap of 26 with a normal lactic acid, and blood glucose of 148 mg/dL [Figure 1]. Arterial blood gas (ABG) revealed a pH of 7.046 and bicarbonate of 3.2. He was treated with an IV bicarbonate drip, IV insulin drip, and high volume IV fluids. He also underwent monitoring with serial ABGs, frequent blood glucose checks, and basic metabolic panels. The HAGMA gradually resolved over the next 48 hours. Additional serology revealed a positive glutamic acid decarboxylase (GAD) antibody; indicative of latent autoimmune DM in adults (LADA). After improvement his glimepiride, dapagliflozin, and metformin were discontinued. He was ultimately transitioned from an IV insulin drip to a basal/bolus insulin regimen at discharge. DISCUSSION: SGLT2i medications enhance excretion and block reabsorption of filtered glucose from the proximal convoluted tubule, resulting in a state of glucose starvation thereby increasing the glucagon/insulin ratio [1]. The HAGMA seen in EDKA is thought to result from increased lipolysis due to the glucagon/insulin imbalance, ultimately leading to ketoacidosis [2]. The mechanism of ketone production in EDKA is similar to DKA; acetoacetic acid reduces to beta-hydroxybutyric acid [2]. EDKA is a rare but known complication in type 2 diabetics who are prescribed SGLT2i therapies. Use of SGLT2i is not recommended in those with autoimmune diabetes by the Food and Drug Administration as ketone-associated complications can be as high as 9% [3]. LADA is an anti-islet cell autoimmune adult-onset DM. In our patient, he was initially misdiagnosed with DM-2; however, his blood work revealed that he had LADA. CONCLUSIONS: As SGLT2i usage becomes increasingly more common, providers should be cognizant of the patient's diabetic history and ensure the correct etiology of their patient's diabetes. Additionally, critical care providers should remain vigilant of the phenomenon of EDKA and its predisposing risk factors. REFERENCE #1: Pfützner A, Klonoff D, Heinemann L, Ejskjaer N, Pickup J. Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy-an emerging problem and solutions offered by diabetes technology. Endocrine. 2017 Apr;56(1):212-216. doi: 10.1007/s12020-017-1264-y. Epub 2017 Mar 17. PMID: 28303514. REFERENCE #2: Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. 2021 Feb 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 32119457. REFERENCE #3: Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1687-93. doi: 10.2337/dc15-0843. Epub 2015 Jun 15. PMID: 26078479; PMCID: PMC4542270. DISCLOSURES: No relevant relationships by Jonathan Ross Ang, source=Web Response No relevant relationships by Parth Patel, source=Web Response No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by Shaili Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response