title: Free dissociable IGF-I: Association with changes in IGFBP-3 proteolysis and insulin sensitivity after surgery.
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.
  
  
  OBJECTIVE
  We hypothesized that serum IGFBP-3-PA increases bioavailability of circulating IGF-I and preserves insulin sensitivity in patients given CHO.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Div of Pediatrics, Dept of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyds Hospital & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Thorell
authors.affiliation: Pediatric Endocrinology Unit, Dept. of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Carlsson-Skwirut
authors.affiliation: Department of Surgery, Orebro University Hospital, Orebro, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ljungqvist
authors.affiliation: Dept. of Molecular Endocrinology, Karolinska Institute and Hospital, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyds Hospital & Department of Surgery, Ersta Hospital, Stockholm, Sweden. Electronic address: jonas.nygren@erstadiakoni.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Nygren
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D013505:Digestive System Surgical Procedures; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control; D011300:Preoperative Care / Q000379:methods; D059748:Proteolysis
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; C583557:IGF1 protein, human; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I
keywords: Free dissociable IGF; IGF bioavaialbility; IGF-I; IGFBP-3; Insulin resistance; Proteolysis