Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

Abstract

Objective :L iver 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 bioactiveI GF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binarycomplex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis. Methods:Seven Caucasian males with liver cirrhosis and seven healthymales matched for age (54.4G 3.2 vs 54.6G 4.4 years) and body mass index( 25.3G 1.2 vs 25.9G 1.3 kg/m 2 )w ere 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 binarycomplex, while bioactiveIGF-I wasmeasured at 0, 30, 60, 120, and 180 min. Results:Incomparison with healthysubjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower,w hile IGFBP-1 (268%) wash igher ( P ! 0.05), IGFBP-2 (172%) tended to be higher ( P O 0.05), and the binarycomplexunchanged ( w 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchangedinb oth study groups during the OGTT.B ioactiveIGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT ( P ! 0.05). As imilar tendency waso bservedi nh ealthyc ontrols ( P Z 0.052). Concomitantly, IGFBP-1, binarycomplex, and IGFBP-1 saturation indexd ecreased significantlyi nb oth groups. The disappearance of the binarycomplex wasa bout twofold faster than that of IGFBP-1 ( P ! 0.05). Conclusion:D espite unchangedc oncentrations of total and free IGF-I, bioactive IGF-I declined significantlya fter an oral glucose load in patients with liverc irrhosis and the same tendency was observedinhealthysubjects. We speculate that the reduction in bioactiveIGF-I mayberelated to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I. 155 285-292 European Journal of Endocrinology

High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly

“…Studies in the rat indicate that IGFBP-1 infusion inhibits muscle protein synthesis in fast-twitch muscle, although this was not shown in the heart (35). Potential determinants of elevated circulating IGFBP-1 in persons at risk for CHF include oxidative stress (15), cytokine activity (36, 37), ephinephrine or norepinephrine (38), and subclinical liver disease or hepatic insulin resistance (39).…”

Normal levels of serum IGF-I: determinants and validity of current reference ranges

“…With the dominant role of the liver in the regulation of total IGF-I levels it is conceivable that baseline levels of total, free and bioactive IGF-I are lower in liver cirrhosis as normal secretion of IGF-I in response to GH stimulation is attenuated [29]. This effect is not overridden by the higher than normal IGFBP-1 and IGFBP-2 levels described under this condition [29].…”

“…With the dominant role of the liver in the regulation of total IGF-I levels it is conceivable that baseline levels of total, free and bioactive IGF-I are lower in liver cirrhosis as normal secretion of IGF-I in response to GH stimulation is attenuated [29]. This effect is not overridden by the higher than normal IGFBP-1 and IGFBP-2 levels described under this condition [29]. We recently demonstrated this close relationship of the degree of liver failure to IGF-I levels in patients with varying degrees of liver cirrhosis where IGF-I levels correlated inversely to the degree of liver damage (Brabant et al, unpublished results).…”

The IGF system after insertion of a transjugular intrahepatic porto-systemic shunt in patients with liver cirrhosis

“…Patients with cirrhosis and portal hypertension are known to have significant changes in their insulin-like growth factor (IGF) system and its interaction with insulin that may play a role for their loss of body mass (6)(7)(8)(9). Therefore, it is an obvious possibility that TIPS changes the prevailing IGF system and insulin levels in a way that contributes towards improved nutrition (10)(11)(12).…”