Abstract

Diabetic ketoacidosis (DKA) is a well-known, serious complication that many patients with type 1 and 2 diabetes face due to either a relative or absolute insulin deficiency. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have gained increased popularity due to their diabetic, cardiovascular, and renal benefits. An associated complication of SGLT2 inhibitors is euglycemic DKA.A 56-year-old male with a history of type 2 diabetes mellitus and peripheral neuropathy presented with right foot pain secondary to a diabetic foot ulcer. The ulcer was present for one year, but the patient noticed increased pain and purulent discharge over the three days prior to presentation. While being treated inpatient for the foot ulcers, the patient repeatedly refused to receive standard hospital diabetes management of insulin injections. He instead insisted to take his home medications against medical advice, which were metformin and Glyxambi® (empagliflozin/linagliptin, Boehringer Ingelheim, Ingelheim am Rhein, Germany). His diabetic foot ulcer was medically managed with IV antibiotics. On day 4 of admission, his anion gap increased to 23 mEq/L, and serum bicarbonate (CO2) decreased to 8 mEq/L, raising concerns of diabetic ketoacidosis. His glucose was 141 mg/dL, his beta-hydroxybutyrate was high at 5.5 mmol/L. An arterial blood gas (ABG) test demonstrated anion gap metabolic acidosis with secondary respiratory alkalosis. A urinalysis demonstrated glucose 1000 mg/dL and ketones of 150 mg/dL. The patient was diagnosed with euglycemic DKA. Due to the patient having normal glucose levels, an insulin drip and a 5% dextrose with 0.45% normal saline drip were started. Basic metabolic profiles were ordered every four hours, with glucose checks every hour. Once the anion gap was closed and his urinary ketones disappeared, the patient transitioned to subcutaneous insulin. He was able to be discharged home with basal subcutaneous insulin and metformin with instructions to avoid SGLT2 inhibitors in the future. Unfortunately, there are currently no guidelines from endocrinology or internal medicine societies regarding the management of euglycemic DKA. As the typical DKA diagnostic criteria of elevated blood glucose level are not present, it is easy to overlook euglycemic DKA. As these SGLT2 inhibitors become more prevalent, careful monitoring of all potential side effects as well as the contraindications are prudent to successful management of complex disease states.

Highlights

  • Diabetic ketoacidosis (DKA) is a well-known, serious complication that many patients with type 1 and 2 diabetes face due to either a relative or absolute insulin deficiency [1]

  • As the typical DKA diagnostic criteria of elevated blood glucose level are not present, it is easy to overlook euglycemic DKA. As these Sodium-glucose cotransporter 2 (SGLT2) inhibitors become more prevalent, careful monitoring of all potential side effects as well as the contraindications are prudent to successful management of complex disease states

  • Evidence has dramatically increased over the past several years based on recent studies, including the EMPAREG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in T2D Patients-Remove Excess Glucose) and the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program have demonstrated significant reductions in major adverse cardiac events (MACE) in patients randomized to receive SGLT2 inhibitor therapy compared with placebo [3, 4]

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Summary

Introduction

Diabetic ketoacidosis (DKA) is a well-known, serious complication that many patients with type 1 and 2 diabetes face due to either a relative or absolute insulin deficiency [1]. DKA with SGLT2 inhibitors was described as 0.1%, rates ranging from 0.16 to 0.76 events per 1000 patientyears in patients with type 2 diabetes [13, 14] These patients typically present with normal or only mildly elevated blood glucose levels (

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