I - THE EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I ON NUTRITIONAL RECOVERY IN THE MALNOURISHED ALCOHOLIC RAT

Background/aims: Alcoholics with severe liver disease (ALD) typically demonstrate the-findings of protein calorie malnutrition, Such an occu rrence might be anticipated with insulin-like growth factor-1 (IGF-1) deficiency. Furthermore, serum levels of IGF-1 are frequently very low in patients with alcoholic liver disease. The present study was under taken to evaluate in an in vivo rat model of alcoholism and malnutriti on, the possibility of a therapeutic application for IGF-1, Methods: C ontrolled injury was induced by 14 days of calorie restriction and alc ohol feeding (phase 1), which induced a 9% loss of body mass. Changes were compared with pair-fed, calorie-restricted controls that lost 7.8 % of body mass and to unrestricted control rate that gained 28% above their pretreatment body mass during the same period. Recovery was eval uated after 28 day's of treatment using various combinations of: (1) h igh calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1, Results: Liver injury was minimal, but protein calorie malnutrition w as moderately severe after phase 1 treatments. During recovery (phase 2), continuous consumption of alcohol - even in the presence of high c alories and IGF-1 treatment-produced an incomplete nutritional recover y and, compared with normal rats, was associated with lower serum IGF- 1 levels. The group treated with all three modalities (high calories, IGF-1, and abstinence from ethanol) had the most rapid acid complete r estoration of body weight. Conclusions: Recovery of nutritional status in the malnourished rat correlates significantly with serum IGF-1 lev els, in the absence of ethanol and with sufficient caloric intake, IGF -1 treatment increased serum IGF-1 concentrations and accelerated nutr itional recovery. Even with adequate calories, ethanol negated this re covery and was associated with lower serum IGF-1 concentrations. Furth er studies, both basic and clinical, are needed to better understand t he mechanisms involved and to establish whether in patients with sever e liver disease IGF-1 treatment would produce an accelerated improveme nt in nutritional status and improve both morbity and mortality. These animal studies suggest that this is the case.