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 t o be due to a decrease in muscle protein synthesis, secondary to insul in 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. Patient s received either 5 mg rhIGF-I (n = 7) or placebo (n = 9), sc, twice d aily. Glucose metabolism was assessed by stable label iv glucose toler ance test, amino acid metabolism by L-[-C-13] leucine turnover, body c omposition by dual energy x-ray absorptiometry and N excretion, and mu scle 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 i ncorporation into protein increased (P < 0.05), and the rate of leucin e oxidation to leucine turnover decreased (P < 0.05), findings indicat ive of increased protein synthesis. Body weight and lean body mass inc reased, whereas percent body fat decreased (P < 0.05). An increase in manual muscle strength of 0.42 +/- 0.30 (P < 0.02) and in neuromuscula r function of 17.5 +/- 11.7 (P < 0.02) occurred in the four patients w ho received a rhIGF-I dose greater than 70 mu g/kg, whereas a more mod est response occurred in the three patients who received a dose less t han 70 mu g/kg. Two patients showed dramatic improvement. Long term rh IGF-I therapy appears to cause metabolic and muscle improvement in opt imally treated MyD patients.