title: Hyperglycemic, high anion-gap metabolic acidosis in patients receiving SGLT-2 inhibitors for diabetes management.
abstract: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a class of antidiabetic medications that improve glycemic control via inhibiting the reabsorption of filtered glucose and are approved for use in type 2 diabetes (T2DM). These drugs have recently been associated with euglycemic diabetic ketoacidosis (DKA). An increasing number of cases of SGLT-2i-associated DKA have occurred in patients with T2DM. Herein, we describe five episodes of hyperglycemic DKA in four type 2 diabetes patients receiving SGLT-2i therapy. Risk for ketoacidosis in our case series was mediated predominately by reduction of insulin dose and insulinopenia. None of the patients reported a history of low carbohydrate diet or alcohol use, and all but one patient had negative glutamic acid decarboxylase antibodies. Resolution of DKA in SGLT-2i treated patients took longer than for T1DM patients with DKA based on literature data. The mechanisms by which SGLT-2i are associated with ketoacidosis are not fully understood and likely involve hyperglucagonemia and other factors. Further studies are needed to elucidate the precise mechanism.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Juliette Sandifer
authors.initials: JS
authors.lastname: Kum-Nji
authors.affiliation: Endocrinology Section, Stratton VA Medical Center, Albany, NY.
authors.forename: Aidar R
authors.initials: AR
authors.lastname: Gosmanov
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Helmut
authors.initials: H
authors.lastname: Steinberg
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Tennessee Health Science Center, Memphis, TN. Electronic address: sdj@uthsc.edu.
authors.forename: Samuel
authors.initials: S
authors.lastname: Dagogo-Jack
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016883:Diabetic Ketoacidosis / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; C089180:SLC5A2 protein, human; D049993:Sodium Chloride Symporter Inhibitors; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
keywords: Autoantibodies; C-peptide; Diabetic ketoacidosis; Hyperglycemia; Insulinopenia; Sodium-glucose cotransporter-2 inhibitors