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CLINICAL STUDY |
1 Medical Department M (Endocrinology and Diabetes) & Medical Research Laboratory, and 2 Medical Department V (Hepatology and Gastroenterology), Clinical Institute, Aarhus University Hospital, Aarhus, Denmark and 3 Metabolism and Nutrition Unit, San Raffaele Scientific Institute, Milano, Italy
(Correspondence should be addressed to J-W Chen; Email: wen{at}iekf.au.dk)
Objective: Liver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome. Therefore, we investigated the dynamic changes in circulating total, free, and bioactive IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binary complex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis.
Methods: Seven Caucasian males with liver cirrhosis and seven healthy males matched for age (54.4 ± 3.2 vs 54.6 ± 4.4 years) and body mass index (25.3 ± 1.2 vs 25.9 ± 1.3 kg/m2) were studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binary complex, while bioactive IGF-I was measured at 0, 30, 60, 120, and 180 min.
Results: In comparison with healthy subjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower, while IGFBP-1 (268%) was higher (P < 0.05), IGFBP-2 (172%) tended to be higher (P > 0.05), and the binary complex unchanged (~100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchanged in both study groups during the OGTT. Bioactive IGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT (P < 0.05). A similar tendency was observed in healthy controls (P = 0.052). Concomitantly, IGFBP-1, binary complex, and IGFBP-1 saturation index decreased significantly in both groups. The disappearance of the binary complex was about twofold faster than that of IGFBP-1 (P < 0.05).
Conclusion: Despite unchanged concentrations of total and free IGF-I, bioactive IGF-I declined significantly after an oral glucose load in patients with liver cirrhosis and the same tendency was observed in healthy subjects. We speculate that the reduction in bioactive IGF-I may be related to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I.
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