title: Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study.
abstract: OBJECTIVE
  Recent data have shown that ectopic fat accumulation in the liver worsens hepatic glucose metabolism, suggesting that fatty liver in patients with type 2 diabetes is a therapeutic target. Glucagon-like peptide (GLP)-1 improves fatty liver, but the effect of dipeptidyl peptidase-4 inhibitor on fatty liver is still unclear. The present pilot study determined the effects of 12-week treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, on liver fat content in type 2 diabetes with fatty liver. We also evaluated intramyocellular lipid (IMCL) and glucose kinetics during oral glucose tolerance test (OGTT) before and after the treatment.
  
  
  METHODS
  The study participants were seven type 2 diabetes patients with fatty liver who were studied at baseline and 12 weeks after sitagliptin treatment. Intrahepatic lipid (IHL) and IMCL were assessed by (1)H magnetic resonance spectroscopy. Glucose kinetics was assessed during double-tracer OGTT (U-[(13)C]-glucose orally and 6,6-[(2)H2]-glucose intravenously).
  
  
  RESULTS
  Sitagliptin significantly reduced glycated hemoglobin (from 7.1 ± 0.2 to 6.5 ± 0.3%, P < 0.005), but had no effects on IHL and IMCL. The glucose level diminished, whereas GLP-1 concentration increased during OGTT at the end of treatment. These changes were not accompanied by significant changes in insulin or glucagon levels. However, long-term sitagliptin treatment partially decreased the rate of appearance of oral glucose during OGTT, but did not affect endogenous glucose production or the rate of disappearance.
  
  
  CONCLUSIONS
  It was found that 12-week sitagliptin treatment improved glycated hemoglobin and glucose excursion during OGTT in type 2 diabetes with fatty liver, independent of changes in lipid accumulation in the liver. This trial was registered with the Japan Clinical Trials Registry (UMIN-CTR000005666).
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Takahiro
authors: T
authors: Watanabe
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Sportology Center, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Yoshifumi
authors: Y
authors: Tamura
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Sportology Center, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Saori
authors: S
authors: Kakehi
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Takashi
authors: T
authors: Funayama
authors: National Research Council (CNR), Institute of Clinical Physiology Pisa, Italy.
authors: Amalia
authors: A
authors: Gastaldelli
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Kageumi
authors: K
authors: Takeno
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Minako
authors: M
authors: Kawaguchi
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Sportology Center, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Risako
authors: R
authors: Yamamoto
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Fumihiko
authors: F
authors: Sato
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Sportology Center, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Shin-Ichi
authors: S
authors: Ikeda
authors: Laboratory of Proteomics and Biomolecular Science, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Hikari
authors: H
authors: Taka
authors: Laboratory of Proteomics and Biomolecular Science, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Tsutomu
authors: T
authors: Fujimura
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Center for Therapeutic Innovations in Diabetes, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Yoshio
authors: Y
authors: Fujitani
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Sportology Center, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Ryuzo
authors: R
authors: Kawamori
authors: Department of Metabolism & Endocrinology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Sportology Center, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Center for Therapeutic Innovations in Diabetes, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Center for Molecular Diabetology, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan ; Center for Beta Cell Biology and Regeneration, Biomedical Research Center, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors: Hirotaka
authors: H
authors: Watada
keywords: Dipeptidyl peptidase-4 inhibitor; Double tracer; Fatty liver