title: Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.
abstract: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level.
  
  
  
  Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment.
  
  
  
  At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables.
  
  
  
  Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.
  
  
  
  UMIN-CTR Clinical Trial UMIN000018151.
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Hiramitsu Heart Clinic, Shiroshita-cho 2-35, Minami-ku, Nagoya, 457-0047, Aichi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hiramitsu
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Omori
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Marenao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Moniwa
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Junnichi
authors.initials: J
authors.lastname: Ishii
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D000068896:Canagliflozin / Q000008:administration & dosage* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D050556:Fatty Acid-Binding Proteins; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009638:Norepinephrine; C493410:FABP4 protein, human; C517652:hemoglobin A1c protein, human