title: Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients.
abstract: To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration.
  
  
  
  Fasting plasma glucose (FPG), insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at day 1 and day 14 after treatment with empagliflozin.
  
  
  
  Empagliflozin caused a 38 mg/dL reduction in FPG concentration in T2DM patients. However, it caused only a small but significant (7 mg/dL) reduction in the FPG concentration in impaired fasting glucose (IFG) subjects and did not affect FPG concentration in normal glucose tolerant (NGT) subjects. Empagliflozin caused a significant increase in mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects. An index that integrates change in plasma glucose, insulin and FFA concentration at day 1 strongly correlates with plasma ketone concentration at day 1 (r = 0.85, P < .001) and day 14 (r = 0.63, r = 0.01) and predicts, with 86% sensitivity and 83% specificity, subjects at the top tertile for plasma ketone concentration after empagliflozin treatment.
  
  
  
  Results of the present study demonstrate that SGLT2 inhibition exerts different metabolic effects in non-diabetic individuals as compared to diabetic patients.
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Hussein
authors.initials: H
authors.lastname: Al Jobori
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daniele
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: John
authors.initials: J
authors.lastname: Adams
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cersosimo
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Curtis
authors.initials: C
authors.lastname: Triplitt
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.affiliation: Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Muhammad
authors.identifier: 0000-0003-4556-1787
authors.initials: M
authors.lastname: Abdul-Ghani
mesh_terms: D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005215:Fasting / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000187:drug effects; D018149:Glucose Intolerance / Q000097:blood* / Q000188:drug therapy; D005951:Glucose Tolerance Test; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007659:Ketones / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005960:Glucosides; D007004:Hypoglycemic Agents; D007659:Ketones; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005934:Glucagon; C570240:empagliflozin
keywords: SGLT2 inhibitor; empagliflozin; fasting plasma glucose; free fatty acid; glucagon; insulin; ketone