title: Changes in Levels of Biomarkers Associated with Adipocyte Function and Insulin and Glucagon Kinetics During Treatment with Dapagliflozin Among Obese Type 2 Diabetes Mellitus Patients.
abstract: OBJECTIVE
  This study aimed to investigate changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics after a meal tolerance test (MTT) during treatment with dapagliflozin among obese type 2 diabetes mellitus (T2DM) patients.
  
  
  METHODS
  T2DM patients with hemoglobin A1c (HbA1c) levels >6.5 % and body mass index (BMI) >25 kg/m2were treated with dapagliflozin 5 mg/day for at least 12 weeks. HbA1c, body weight, ketone bodies, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) were measured before and after treatment with dapagliflozin. A subset of patients underwent an MTT.
  
  
  RESULTS
  Of 27 participating patients (mean age 47.9 years; 17 males), five were drug-naive and 22 were treated with other antidiabetic agents, including insulin and glucagon-like peptide-1 (GLP-1) receptor agonists. Following treatment with dapagliflozin, HbA1c levels significantly improved (7.44 ± 0.56 to 6.70 ± 0.0.57 %; p < 0.01), body weight significantly decreased (90.9 ± 16.5 to 87.1 ± 15.9 kg; p < 0.01), ketone bodies increased, adiponectin significantly increased, and high-sensitivity CRP tended to decrease. During the MTT, blood glucose ΔAUC2significantly decreased, glucagon ΔAUC2increased, and immunoreactive insulin (IRI) did not change in 11 of 27 patients.
  
  
  CONCLUSIONS
  Although ketone bodies increased significantly, adiponectin increased and high-sensivity CRP decreased significantly. These findings suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors may potentially improve adipocyte function in treating obese T2DM patients.
authors.affiliation: OKM Okamoto Medical Clinic, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of General Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan. Yokokawa@pa3.so-net.ne.jp.
authors.forename: Hirohide
authors.initials: H
authors.lastname: Yokokawa
authors.affiliation: Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Aizubange Town, Fukushima, Japan.|Department of Tumor and Host Bioscience, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sanada
authors.affiliation: OKM Okamoto Medical Clinic, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Naito
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D003404:Creatinine / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D005960:Glucosides / Q000008:administration & dosage / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007657:Ketone Bodies; D008297:Male; D008687:Metformin; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1
chemical_list: D052242:Adiponectin; D001559:Benzhydryl Compounds; D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D003404:Creatinine; D005934:Glucagon; D000067757:Glucagon-Like Peptide-1 Receptor; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D007657:Ketone Bodies; D008687:Metformin; D017395:Plasminogen Activator Inhibitor 1; C000593833:GLP1R protein, human; C051321:SERPINE1 protein, human; C517652:hemoglobin A1c protein, human; C529054:dapagliflozin