Document 0262
 DOCN  M9440262
 TI    Anabolic effects of recombinant insulin-like growth factor-I in
       cachectic patients with the acquired immunodeficiency syndrome.
 DT    9404
 AU    Lieberman SA; Butterfield GE; Harrison D; Hoffman AR; Medical Service,
       Department of Veterans Affairs Medical Center,; Palo Alto, California
       94304.
 SO    J Clin Endocrinol Metab. 1994 Feb;78(2):404-10. Unique Identifier :
       AIDSLINE MED/94149144
 AB    The loss of lean body mass accompanying acquired immunodeficiency
       syndrome (AIDS)-associated cachexia is refractory to current modes of
       therapy. GH and insulin-like growth factor-I (IGF-I) stimulate protein
       accretion, but resistance to GH action has been reported in malnutrition
       and infection. We hypothesized that GH resistance occurs in
       AIDS-associated cachexia, but that treatment with IGF-I would be
       anabolic. A single injection of GH produced a smaller increase in
       circulating IGF-I in 21 patients with AIDS compared to that in 23
       age-matched controls (141 +/- 15 vs. 194 +/- 15 micrograms/L; P < 0.02),
       indicating partial GH resistance. Ten subjects received either low or
       high dose iv recombinant IGF-I 12 h daily for 10 days. Cumulative
       nitrogen retention was positive for both dosage groups (low dose, 15.42
       +/- 6.37 g; high dose, 3.62 +/- 4.15 g), but a significant increase in
       daily nitrogen retention occurred only in the low dose group on days 2,
       4, 5, 6, and 7. Nitrogen balance and protein turnover (estimated by
       [13C]leucine and [15N] glycine kinetics) during the final 3 days of
       treatment were unchanged compared to baseline values, confirming the
       transient nature of the anabolic response. Repeated administration of
       IGF-I decreased IGF-binding protein-3 levels, producing lower
       intrainfusion levels of IGF-I and limiting its therapeutic efficacy. The
       basal metabolic rate increased with high dose IGF-I and may have
       contributed to the lack of anabolic effect. We conclude that partial GH
       resistance occurs in AIDS-associated cachexia. Treatment with low dose
       recombinant IGF-I produces significant, but transient, nitrogen
       retention. Alternate routes of IGF-I administration or coadministration
       with GH may prevent attenuation of IGF-I action.
 DE    Acquired Immunodeficiency Syndrome/*COMPLICATIONS/METABOLISM  Adult
       Anthropometry  Antigens, CD4/ANALYSIS  Body Mass Index
       Cachexia/*COMPLICATIONS/*DRUG THERAPY/METABOLISM  Carrier Proteins/BLOOD
       Comparative Study  Dose-Response Relationship, Drug  Energy
       Metabolism/PHYSIOLOGY  Glycine/METABOLISM  Human  Insulin-Like Growth
       Factor I/ADVERSE EFFECTS/ANALYSIS/  *THERAPEUTIC USE  Leucine/METABOLISM
       Lymphocytes/IMMUNOLOGY/PATHOLOGY  Male  Middle Age
       Nitrogen/METABOLISM/URINE  Recombinant Proteins/ADVERSE
       EFFECTS/BLOOD/THERAPEUTIC USE  Somatotropin/PHARMACOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Time Factors  Tumor
       Necrosis Factor/ANALYSIS  CLINICAL TRIAL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).