Identification of Proteins Associated with the Early Restoration of Insulin Sensitivity After Biliopancreatic Diversion

J Clin Endocrinol Metab. 2020 Nov 1;105(11):e4157-e4168. doi: 10.1210/clinem/dgaa558.

Abstract

Context: Insulin resistance (IR) is a risk factor for type 2 diabetes, diabetic kidney disease, cardiovascular disease and nonalcoholic steatohepatitis. Biliopancreatic diversion (BPD) is the most effective form of bariatric surgery for improving insulin sensitivity.

Objective: To identify plasma proteins correlating with the early restoration of insulin sensitivity after BPD.

Design: Prospective single-center study including 20 insulin-resistant men with morbid obesity scheduled for BPD. Patient characteristics and blood samples were repeatedly collected from baseline up to 4 weeks postsurgery. IR was assessed by homeostatic model assessment for insulin resistance (HOMA-IR), Matsuda Index, and by studying metabolic profiles during meal tolerance tests. Unbiased proteomic analysis was performed to identify plasma proteins altered by BPD. Detailed plasma profiles were made on a selected set of proteins by targeted multiple reaction monitoring mass spectrometry (MRM/MS). Changes in plasma proteome were evaluated in relation to metabolic and inflammatory changes.

Results: BPD resulted in improved insulin sensitivity and reduced body weight. Proteomic analysis identified 29 proteins that changed following BPD. Changes in plasma levels of afamin, apolipoprotein A-IV (ApoA4), and apolipoprotein A-II (ApoA2) correlated significantly with changes in IR.

Conclusion: Circulating levels of afamin, ApoA4, and ApoA2 were associated with and may contribute to the rapid improvement in insulin sensitivity after BPD.

Trial registration: ClinicalTrials.gov NCT01151917.

Keywords: afamin; apolipoprotein A-II; apolipoprotein A-IV; biliopancreatic diversion; insulin resistance; proteomic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biliopancreatic Diversion*
  • Blood Glucose / metabolism
  • Body Mass Index
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Obesity, Morbid / blood*
  • Obesity, Morbid / surgery
  • Proteomics

Substances

  • Blood Glucose

Associated data

  • ClinicalTrials.gov/NCT01151917