I: the effects of recombinant human insulin-like growth factor-1 on nutritional recovery in the malnourished alcoholic rat.

Abstract

Alcoholics with severe liver disease (ALD) typically demonstrate the findings of protein calorie malnutrition. Such an occurrence 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 undertaken to evaluate in an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF-1. Controlled injury was induced by 14 days of calorie restriction and alcohol 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 rats that gained 28% above their pretreatment body mass during the same period. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1. Liver injury was minimal, but protein calorie malnutrition was moderately severe after phase 1 treatments. During recovery (phase 2), continuous consumption of alcohol--even in the presence of high calories and IGF-1 treatment--produced an incomplete nutritional recovery 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 and complete restoration of body weight. Recovery of nutritional status in the malnourished rat correlates significantly with serum IGF-1 levels. In the absence of ethanol and with sufficient caloric intake, IGF-1 treatment increased serum IGF-1 concentrations and accelerated nutritional recovery. Even with adequate calories, ethanol negated this recovery and was associated with lower serum IGF-1 concentrations. Further studies, both basic and clinical, are needed to better understand the mechanisms involved and to establish whether in patients with severe liver disease IGF-1 treatment would produce an accelerated improvement in nutritional status and improve both morbity and mortality. These animal studies suggest that this is the case.