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 12months 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 3months (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 3months 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.