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Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy--a clinical research center study.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 1995 Dec; Vol. 80 (12), pp. 3715-23. - Publication Year :
- 1995
-
Abstract
- Muscle weakness and wasting in myotonic dystrophy (MyD) are believed to be due to a decrease in muscle protein synthesis, secondary to insulin resistance. A 4-month, randomized, double blind, placebo-controlled trial was undertaken to assess whether recombinant human insulin-like growth factor I (rhIGF-I) may overcome the insulin resistance. Patients received either 5 mg rhIGF-I (n = 7) or placebo (n = 9), sc, twice daily. Glucose metabolism was assessed by stable label iv glucose tolerance test, amino acid metabolism by L-[13C] leucine turnover, body composition by dual energy x-ray absorptiometry and N excretion, and muscle response by manual muscle strength and neuromuscular function. In the treated group, the insulin sensitivity index, insulin action, and glucose disposal all increased (P < 0.05). Leucine flux and leucine incorporation into protein increased (P < 0.05), and the rate of leucine oxidation to leucine turnover decreased (P < 0.05), findings indicative of increased protein synthesis. Body weight and lean body mass increased, whereas percent body fat decreased (P < 0.05). An increase in manual muscle strength of 0.42 +/- 0.30 (P < 0.02) and in neuromuscular function of 17.5 +/- 11.7 (P < 0.02) occurred in the four patients who received a rhIGF-I dose greater than 70 micrograms/kg, whereas a more modest response occurred in the three patients who received a dose less than 70 micrograms/kg. Two patients showed dramatic improvement. Long term rhIGF-I therapy appears to cause metabolic and muscle improvement in optimally treated MyD patients.
- Subjects :
- Adult
Body Composition
Double-Blind Method
Female
Glucose metabolism
Glucose Tolerance Test
Humans
Insulin-Like Growth Factor Binding Protein 3 metabolism
Insulin-Like Growth Factor I adverse effects
Insulin-Like Growth Factor I metabolism
Leucine metabolism
Male
Middle Aged
Muscles physiopathology
Recombinant Proteins
Reference Values
Insulin-Like Growth Factor I therapeutic use
Myotonic Dystrophy drug therapy
Myotonic Dystrophy physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 80
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 8530624
- Full Text :
- https://doi.org/10.1210/jcem.80.12.8530624