title: I: the effects of recombinant human insulin-like growth factor-1 on nutritional recovery in the malnourished alcoholic rat.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterans Affairs Medical Center, and Department of Medicine, University of Cincinnati Medical Center, Ohio 45220, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Mendenhall
authors.forename: G A
authors.initials: GA
authors.lastname: Roselle
authors.forename: C J
authors.initials: CJ
authors.lastname: Grossman
authors.forename: P
authors.initials: P
authors.lastname: Gartside
mesh_terms: D000428:Alcohol Drinking; D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D004195:Disease Models, Animal; D002149:Energy Intake; D005247:Feeding Behavior; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use*; D009748:Nutrition Disorders / Q000188:drug therapy*; D009752:Nutritional Status / Q000187:drug effects; D011502:Protein-Energy Malnutrition / Q000188:drug therapy; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I