Free dissociable IGF-I: Association with changes in IGFBP-3 proteolysis and insulin sensitivity after surgery

Clin Nutr. 2016 Apr;35(2):408-413. doi: 10.1016/j.clnu.2015.03.003. Epub 2015 Mar 13.

Abstract

Background: Patients receiving a carbohydrate drink (CHO) before major abdominal surgery display improved insulin sensitivity postoperatively and increased proteolysis of IGFBP-3 (IGFBP-3-PA) compared to patients undergoing similar surgery after overnight fasting.

Aims: We hypothesized that serum IGFBP-3-PA increases bioavailability of circulating IGF-I and preserves insulin sensitivity in patients given CHO.

Design: Matched control study.

Methods: At Karolinska University Hospital, patients given CHO before major elective abdominal surgery (CHO,n = 8) were compared to patients undergoing similar surgical procedures after overnight fasting (FAST,n = 10). Results from two different techniques for determination of free-dissociable IGF-I (fdIGF-I) were compared with changes in IGFBP-3-PA and insulin sensitivity.

Results: Postoperatively, CHO displayed 18% improvement in insulin sensitivity (hyperinsulinemic clamp) and increased IGFBP-3-PA vs. FAST. As determined by IRMA, fdIGF-I increased by 48 ± 25% in CHO while fdIGF-I decreased by 13 ± 18% in FAST (p < 0.01 vs. CHO, when corrected for duration of surgery). However, fdIGF-I determined by ultra-filtration decreased similarly in both groups (-22 ± 8% vs. -25 ± 8%, p = 0.8) and IGFBP-1 increased similarly in both groups. Patients with less insulin resistance after surgery demonstrated larger increases in fdIGF-I by IRMA (r = 0.58, p < 0.05). Fifty-three % of the variability of the changes in fdIGF-I by IRMA could be explained by changes in IGFBP-3-PA and total IGF-I levels (p < 0.05), while IGFBP-1 did not contribute significantly.

Conclusion: During conditions when serum IGF-I bioavailability is regulated by IGFBP-3 proteolysis, measurements of fdIGF-I by IRMA is of physiological relevance as it correlates with the associated changes in insulin sensitivity.

Keywords: Free dissociable IGF; IGF bioavaialbility; IGF-I; IGFBP-3; Insulin resistance; Proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Mass Index
  • Case-Control Studies
  • Dietary Carbohydrates / administration & dosage*
  • Digestive System Surgical Procedures*
  • Female
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Linear Models
  • Male
  • Middle Aged
  • Postoperative Complications / prevention & control
  • Preoperative Care / methods
  • Proteolysis*

Substances

  • Blood Glucose
  • Dietary Carbohydrates
  • IGF1 protein, human
  • IGFBP1 protein, human
  • IGFBP3 protein, human
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I