Lower fetuin-A, retinol binding protein 4 and several metabolites after gastric bypass compared to sleeve gastrectomy in patients with type 2 diabetes

PLoS One. 2014 May 6;9(5):e96489. doi: 10.1371/journal.pone.0096489. eCollection 2014.


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.

Aim: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / surgery*
  • Female
  • Gastrectomy / methods
  • Gastric Bypass / methods
  • Humans
  • Insulin Resistance / physiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Proteomics / methods
  • Retinol-Binding Proteins, Plasma / metabolism*
  • Weight Loss / physiology
  • alpha-2-HS-Glycoprotein / metabolism*


  • AHSG protein, human
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • alpha-2-HS-Glycoprotein

Grants and funding

This work was supported by the Jens Henrick Jensen fund and the NovoNordisk Diabetes grant fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.