SGLT2 INHIBITOR-INDUCED EUGLYCEMIC DIABETIC KETOACIDOSIS

Abstract

SESSION TITLE: Critical Care 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Diabetic Ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. While most cases of DKA present with hyperglycemia coupled with anion-gap metabolic acidosis and ketonemia, some cases, referred to as “Euglcyemic DKA”, may present with normal blood glucose levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of oral hypoglycemic agents which target the SGLT-2 transporter in renal proximal convoluted tubules, preventing reabsorption of glucose from urine into the bloodstream. We present a patient of Type 2 Diabetes Mellitus (T2DM) who was on an SGLT-2 inhibitor and developed euglycemic ketoacidosis. CASE PRESENTATION: A 38 year old male with a past history of T2DM accompanied with neuropathy, peripheral vascular disease and hypertension, presented to the ED with a three day history of nausea and vomiting. His home medications included empagliflozin, metformin and insulin detemir. Our patient reported medication compliance and denied recent alcohol consumption. He was afebrile; BP 159/71 mmHg and pulse 118 BPM. On exam, patient appeared in mild distress with abdominal tenderness. Labs revealed an anion-gap of 24, blood glucose of 176 g/dL with a normal BUN, creatinine and lactic acid. Urinalysis revealed ketones and glycosuria. At this time, euglycemic DKA was highly suspected. He was admitted to the MICU and DKA protocol was initiated. He was administered normal saline, Dextrose 5% in water with IV insulin drip at 0.1U/kg/hr with concurrent potassium supplementation. After his anion gap closed within 24 hours, our patient was switched to a basal and pre-meal insulin regimen. DISCUSSION: Euglycemic DKA is characterized by normal to mildly elevated blood glucose levels and can be missed due to the absence of hyperglycemia that’s usually seen in DKA. SGLT-2 inhibitors lower blood glucose levels by increasing urinary glucose excretion, which reduces the stimulus for pancreatic β-cell insulin secretion. Insulin normally acts to inhibit hormone-sensitive lipase, thereby decreasing the generation of free-fatty acids that serve as a substrate for β-oxidation and ketogenesis. With SGLT-2 inhibitors, marked glycosuria and resultant decreased insulin secretion results in uninhibited lipolysis, increased β-oxidation and ketogenesis. As a result of decreased blood glucose levels, pancreatic α-cells are stimulated to increase glucagon secretion, further promoting lipolysis and ketogenesis. CONCLUSIONS: Management of SGLT-2 inhibitor euglycemic DKA follows the American Diabetes Association recommendations with focus on intravenous fluids, insulin and electrolyte management. However, initiation of dextrose in IV fluids is imperative considering the euglycemic nature of the pathogenesis. Upon stabilization and subsequent discharge, patients should discontinue SGLT-2 inhibitors and maintain adequate hydration going forward. Reference #1: LexiComp Online. 2016 Wolters Kluwer Clinical Drug Information Inc. July 29, 2016. Reference #2: Peters, Anne L, Buschur EO, Buse JB, Cohan P, Dinner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment with Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015; 38:1687-1693 DISCLOSURES: No relevant relationships by Ambreesh Chawla, source=Web Response no disclosure on file for Austin Healy; No relevant relationships by Minha Kim, source=Web Response no disclosure on file for Sunil Sapru