title: The IGF-Axis and Diabetic Retinopathy Before and After Gastric Bypass Surgery.
abstract: Laparoscopic gastric bypass (LGB) abruptly causes remission of type 2 diabetes (T2D). Such dramatic metabolic changes have previously been found to cause worsening of diabetic retinopathy (DR) and circulating insulin-like growth factor I (IGF-I) has been suggested as a causal mediator. We aimed to evaluate baseline imbalances in the circulating IGF-system and changes after LGB in patients with T2D.
  
  
  
  Prospective ocular examinations and measurement of the IGF-axis before and 3 and 12 months after LGB. IGF-bioactivity was measured by cell-based IGF-I receptor (IGF-IR) kinase activation assay (bioactive IGF). Total IGF-I, IGF-II and IGF binding protein (IGFBP) 1 and 3 were determined by immunoassays.
  
  
  
  At baseline, 18 of 36 patients presented with DR. These patients had higher levels of bioactive IGF (p = 0.03) than patients without DR and this association was strengthened in multivariate analysis (p = 0.006). Three patients had worsening of DR, unrelated to other markers. In univariate analysis, bioactive IGF increased at 3 months (p = 0.05) but this change became insignificant in multivariate analysis (p = 0.11). IGFBP-1 increased whereas IGFBP-3 and total IGF-II decreased at the two postoperative visits (p ≤ 0.001). Total IGF-I showed no significant changes. HbA1c, glucose, HOMA-IR and lipids improved after surgery. Two patients did not complete the 12-month visit.
  
  
  
  In obese T2D patients, bioactive IGF is a potential biomarker for DR and levels tended to increase 3 months after bariatric surgery. IGFBP-1 increased while IGFBP-3 and total IGF-II decreased postoperatively, but these changes were unassociated with the development of DR. Markers of the metabolic syndrome improved.
authors.affiliation: Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark. troels@brynskov.com.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. troels@brynskov.com.
authors.forename: Troels
authors.identifier: 0000-0002-5250-4257
authors.initials: T
authors.lastname: Brynskov
authors.affiliation: Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark.
authors.forename: Caroline Schmidt
authors.initials: CS
authors.lastname: Laugesen
authors.affiliation: Department of Bariatric Surgery, Zealand University Hospital Køge, Køge, Denmark.
authors.forename: Andrea Karen
authors.initials: AK
authors.lastname: Floyd
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.|Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben Lykke
authors.initials: TL
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism* / Q000601:surgery*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D015390:Gastric Bypass / Q000534:rehabilitation; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins
keywords: Bariatric surgery; Bioactive IGF; Diabetes; Diabetic retinopathy; Gastric bypass surgery; IGF-I; IGF-II; IGFBP-1; IGFBP-3