Anabolic effects of recombinant insulin-like growth factor-I in cachectic patients with the acquired immunodeficiency syndrome.
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.
Lieberman
S A
SA
Medical Service, Department of Veterans Affairs Medical Center, Palo Alto, California 94304.
Butterfield
G E
GE
Harrison
D
D
Hoffman
A R
AR
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000378:metabolism; D000328:Adult; D000886:Anthropometry; D015992:Body Mass Index; D015704:CD4 Antigens / Q000032:analysis; D002100:Cachexia / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000502:physiology; D005998:Glycine / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D007930:Leucine / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism / Q000652:urine; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015704:CD4 Antigens; D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D007930:Leucine; D009584:Nitrogen; D005998:Glycine