title: Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial.
abstract: OBJECTIVE
  Zinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients.
  
  
  METHODS
  A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations.
  
  
  RESULTS
  Circulating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 or P<0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-α level (P<0.05).
  
  
  CONCLUSIONS
  A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Zerong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Harvest F
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA liling31@hotmail.com gangyiyang@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA liling31@hotmail.com gangyiyang@163.com.
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D029589:Seminal Plasma Proteins / Q000097:blood*; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D029589:Seminal Plasma Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000090203:Zn-Alpha-2-Glycoprotein; D000068900:Sitagliptin Phosphate