title: Lower fetuin-A, retinol binding protein 4 and several metabolites after gastric bypass compared to sleeve gastrectomy in patients with type 2 diabetes.
abstract: BACKGROUND
  Bypass of foregut secreted factors promoting insulin resistance is hypothesized to be one of the mechanisms by which resolution of type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery.
  
  
  OBJECTIVE
  To identify insulin resistance-associated proteins and metabolites which decrease more after GBP than after sleeve gastrectomy (SG) prior to diabetes remission.
  
  
  METHODS
  Fasting plasma from 15 subjects with T2D undergoing GBP or SG was analyzed by proteomic and metabolomic methods 3 days before and 3 days after surgery. Subjects were matched for age, BMI, metformin therapy and glycemic control. Insulin resistance was calculated using homeostasis model assessment (HOMA-IR). For proteomics, samples were depleted of abundant plasma proteins, digested with trypsin and labeled with iTRAQ isobaric tags prior to liquid chromatography-tandem mass spectrometry analysis. Metabolomic analysis was performed using gas chromatography-mass spectrometry. The effect of the respective bariatric surgery on identified proteins and metabolites was evaluated using two-way analysis of variance and appropriate post-hoc tests.
  
  
  RESULTS
  HOMA-IR improved, albeit not significantly, in both groups after surgery. Proteomic analysis yielded seven proteins which decreased significantly after GBP only, including Fetuin-A and Retinol binding protein 4, both previously linked to insulin resistance. Significant decrease in Fetuin-A and Retinol binding protein 4 after GBP was confirmed using ELISA and immunoassay. Metabolomic analysis identified significant decrease of citrate, proline, histidine and decanoic acid specifically after GBP.
  
  
  CONCLUSIONS
  Greater early decrease was seen for Fetuin-A, Retinol binding protein 4, and several metabolites after GBP compared to SG, preceding significant weight loss. This may contribute to enhanced T2D remission observed following foregut bypass procedures.
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand; School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Mia
authors.initials: M
authors.lastname: Jüllig
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Shelley
authors.initials: S
authors.lastname: Yip
authors.affiliation: Department of Medicine, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Special Administrative Region, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Smith
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand; School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Martin
authors.initials: M
authors.lastname: Middleditch
authors.affiliation: Department of Surgery, North Shore Hospital, Auckland, New Zealand.
authors.forename: Michael
authors.initials: M
authors.lastname: Booth
authors.affiliation: Department of Surgery, Middlemore Hospital, Auckland, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: Babor
authors.affiliation: Department of Surgery, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Grant
authors.initials: G
authors.lastname: Beban
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Rinki
authors.initials: R
authors.lastname: Murphy
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D005743:Gastrectomy / Q000379:methods; D015390:Gastric Bypass / Q000379:methods; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D015431:Weight Loss / Q000502:physiology; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: C556354:AHSG protein, human; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D060749:alpha-2-HS-Glycoprotein