Troels Brynskov1,2, Caroline Schmidt Laugesen3, Andrea Karen Floyd4, Jan Frystyk5,6, Torben Lykke Sørensen3,7. 1. Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark. troels@brynskov.com. 2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. troels@brynskov.com. 3. Department of Ophthalmology, Zealand University Hospital Roskilde, Roskilde, Denmark. 4. Department of Bariatric Surgery, Zealand University Hospital Køge, Køge, Denmark. 5. Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 6. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 7. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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