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

Hyperinsulinemic euglycemic clamps were performed on six patients with compensated alcoholic cirrhosis and on six normal comparison subjects. As in previous studies, glucose uptake in the cirrhotic patients was only 21% of the comparison value. The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001). The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95). The clamps were repeated with a somatostatin infusion to suppress GH secretion. IGFBP-1 increased in both groups, especially in the cirrhotic subjects. Insulin sensitivity increased in the normal subjects but was unchanged in the cirrhotic patients. Following GH treatment (0.13 U/kg/d for 5 days), the clamps were repeated. GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05). Glucose uptake in the cirrhotic patients remained only 29% of the comparison value, but the change in their insulin sensitivity was inversely correlated with the change in their IGFB-1 levels (r = -.84). These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis.