Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy--a clinical research center study.
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.
Department of Pediatrics, New York Hospital-Cornell Medical Center, New York 10021, USA.
E
E
Vlachopapadopoulou
J J
JJ
Zachwieja
J M
JM
Gertner
D
D
Manzione
D M
DM
Bier
D E
DE
Matthews
A E
AE
Slonim
D000328:Adult; D001823:Body Composition; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D007930:Leucine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000503:physiopathology; D009223:Myotonic Dystrophy / Q000188:drug therapy* / Q000503:physiopathology*; D011994:Recombinant Proteins; D012016:Reference Values
D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007930:Leucine; D005947:Glucose