High insulin-like growth factor binding protein 1 levels in cirrhosis: Link with insulin resistance

Abstract

1endocrine fashion, and their bioactivity is greatly modulated Hyperinsulinemic euglycemic clamps were performed by their binding proteins. Thus, GH, which reduces sensitivon six patients with compensated alcoholic cirrhosis and ity to insulin, normally stimulates the secretion of IGF-I, on six normal comparison subjects. As in previous studwhich increases insulin sensitivity. ies, glucose uptake in the cirrhotic patients was only Several roles have been suggested for the six IGF-binding 21% of the comparison value. The cirrhotic patients had proteins (IGFBPs) identified thus far. These include limiting high growth hormone (GH) and low insulin-like growth the bioactivity of the IGFs to protect against hypoglycemia, factor-I (IGF-I) levels, with low insulin-like growth facregulation of the stability or clearance rate of the IGFs, and tor-binding protein (IGFBP)-3 levels, but surprisingly modulation of the action of the IGFs at a cellular level.2 high IGFBP-1 levels (26.8 { 8.4 mgH vs. 3.2 { 0.2 mg/L, P IGFBP-3 is the most abundant in serum and binds 95% of õ .001). The log IGFBP-1 level was inversely correlated circulating IGF-I and -II in a ternary complex that is highly with the log insulin sensitivity (r Å 0.95). The clamps stable and probably serves to limit the bioavailability of the were repeated with a somatostatin infusion to suppressIGFs. IGFBP-3 is produced by the liver and by most other GH secretion. IGFBP-1 increased in both groups, espetissues in response to IGF-I and GH. 2 IGFBP-1 is produced cially in the cirrhotic subjects. Insulin sensitivity inmainly by the liver and is the only IGFBP that displays rapid creased in the normal subjects but was unchanged in regulation with serum levels that vary rapidly in response the cirrhotic patients. Following GH treatment (0.13 U/ to meals. Levels of IGFBP-1 are high in fetal life, fall precipikg/d for 5 days), the clamps were repeated. GH, IGF-I, tously at gestation, and then show a progressive age-related and IGFBP-3 levels were now similar in the two groups; decline in normal individuals. High levels have been found IGFBP-1 levels decreased in the cirrhotic patients but in prolonged fasting, prolonged exercise, in anorexia nervosa, remained fivefold higher than the comparison value in intensive care patients, in chronic renal failure, and in (10.6 { 3.7 vs. 2.1 { 0.4, P õ .05). Glucose uptake in the insulin-dependent diabetes mellitus. 4 IGFBP-1 levels are cirrhotic patients remained only 29% of the comparison lowered by insulin. Low levels have been found in obesity value, but the change in their insulin sensitivity was and polycystic ovary syndrome. IGFBP-1 is thought to limit inversely correlated with the change in their IGFBP-1 the bioactivity of IGF-I by preventing its binding to cell memlevels (r Å 0.84). These results suggest an important role branes. 4 Less is known about the other binding proteins.

Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis

“…50 Low IGF-1 and high IGFBP-1 levels have been described previously in association with cirrhosis and insulin resistance. [51][52][53] There are no published data concerning the relative abundance of IGFBP-1 in patients with NASH who do not have cirrhosis. Further studies in a noncirrhotic population of patients with steatosis and NASH would be required to determine whether NAFLD/ NASH generally is associated with altered expression of IGFBP-1 or other mediators of insulin action/sensitivity.…”

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

“…Indeed, in comparison to healthysubjects, increasedcirculating levels of IGFBP-1, but lower total and free IGF-I, are characteristic features of liver cirrhosis (15)(16)(17)(18)(19). Furthermore, one of the major health problems in cirrhotic patients is malnutrition, whichexertsaserious adverse effect on clinical outcome.…”

“…Moreover, it is well recognized that most cirrhotic patients are intolerant of oral glucose,evenw hen their fasting blood glucose concentrationsa re normal (23,24).T his appearst ob et he result of impaired insulin secretion and insulin sensitivity (25).Asaconsequence of reduced hepatic IGF-I-producing capacity,e levated IGFBP-1,a nd loweri nsulin sensitivity, it mayb e anticipated that in patientsw ith liver cirrhosis, the responsiveness of the IGF system to an oral glucose challenge mayb ed ifferent from thatf ound in normal healthys ubjects (19,26).H owever,s uchs tudies have not yetb een performed. Therefore, the objectiveo ft he present study wast oc ompare the dynamicc hanges in circulatingtotal, free, and bioactiveIGF-I, and IGFBP-1 during an oral glucose tolerance test (OGTT)inpatients with liver cirrhosis and healthycontrols.…”

Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen

“…Elevated IGFBP1 is also present in CLD, and may occur to block the activity of free IGF-I. 43 In conclusion, this study has demonstrated the presence of insulin resistance in ALF, by the presence of impaired peripheral glucose utilization and a failure to fully suppress endogenous glucose production during a hyperinsulinemic euglycemic clamp.…”