Normalisation of insulin-like growth factor-I does not improve insulin action in cirrhosis

作者：Nielsen Michael F^*; Aagaard Niels K; Grofte Thorbjorn; Frystyk Jan; Greisen Jacob; Christiansen Jens S; Holland Fischer Peter; Vilstrup Hendrik

来源：Liver International, 2011, 31(10): 1511-1518.

DOI：10.1111/j.1478-3231.2011.02599.x

• cirrhosis of the liver
• IGF-I
• insulin resistance

Background & Aims: Cirrhosis of the liver is characterised by insulin resistance and low levels of insulin-like growth factor I (IGF-I). Lack of IGF-I may contribute to this insulin resistance, as IGF-I increases insulin sensitivity. This study aimed to determine the effects of normalisation of IGF-I on insulin action in cirrhosis. Methods: This article is a randomised sequence-crossover placebo controlled study. Eight patients with cirrhosis and eight controls were studied following treatment with IGF-I (50 mu g/kg twice daily) or saline. Insulin action, glucose utilisation and endogenous glucose production were measured during the euglycaemic hyperinsulinaemic clamp. Results: The patients with cirrhosis had normal fasting glucose level, but increased levels of insulin (P < 0.05) and C-peptide (P < 0.05). Insulin resistance resulted from a defect in glycogen synthesis, whereas insulin-mediated suppression of glucose production was unaltered. In cirrhosis, IGF-I treatment normalised free (from 0.07 +/- 0.01 to 0.26 +/- 0.05 mu g/L) and total IGF-I (from 73 +/- 6 to 250 +/- 39 mu g/L), whereas in controls, the IGF-I level increased into the upper physiological range (free IGF-I from 0.23 +/- 0.02 to 0.61 +/- 0.06 mu g/L; total IGF-I from 200 +/- 19 to 500 +/- 50 mu g/L) (all P-values < 0.05). In cirrhosis, IGF-I treatment did not change fasting glucose, insulin or C-peptide levels (P > 0.05). In the controls, insulin and C-peptide levels decreased (P < 0.05). IGF-I treatment did not improve insulin sensitivity in cirrhosis. Conclusions: Because normalisation of IGF-I levels did not affect insulin sensitivity lack of IGF-I is unlikely to result in insulin resistance in cirrhosis. IGF-I supplementation is therefore unlikely to improve insulin action in patients with cirrhosis.

• 出版日期2011-11