Effect of insulinlike growth factor-1 treatment in children with cystic fibrosis.
OBJECTIVE
Malnutrition is common in cystic fibrosis (CF) and adversely affects survival. Because insulinlike growth factor-1 (IGF-1) has insulinlike effects in terms of carbohydrate metabolism and is growth promoting, the authors hypothesized that its use would increase linear growth rate and decrease insulin requirements in children with CF.


METHODS
The authors used a double-blind placebo-controlled crossover design. Seven prepubertal children aged 9.6 to 13 years (5 boys and 2 girls) were treated with placebo or IGF-1 for 6 months. After a 6-month washout period, patients received the alternative therapy for 6 months. The primary outcome measure was linear growth rate. Secondary outcome measures were changes in body mass index, body composition determined by dual energy x-ray absorptiometry, forced expiratory volume (FEV(1)), and the blood glucose/insulin ratio.


RESULTS
The mean height z score at baseline was -1.5 +/- 0.8. At entry, the mean serum IGF-1 level was 124 +/- 25 ng/mL (normal range, 110-771 ng/mL). With treatment, mean serum IGF-1 levels increased twofold to threefold for all patients. The half-life for IGF-1 was 10.3 hours. We observed no significant difference in linear growth rate, weight gain, rate of accretion of lean body mass, or mean FEV(1) during treatment with IGF-1 compared with placebo. The glucose/insulin ratio, an indirect index of insulin sensitivity, was significantly increased with IGF-1 treatment compared with placebo ( P < 0.02). No adverse events related to IGF-1 were detected.


CONCLUSIONS
Treatment with IGF-1 for 6 months did not promote linear growth in prepubertal children with CF. However, the glucose/insulin ratio was increased without changing blood glucose levels with IGF-1 treatment suggesting increased insulin sensitivity.
Bucuvalas
J C
JC
Division of Gastroenterology and Nutrition, Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A. john.buc@chmcc.org
Chernausek
S D
SD
Alfaro
M P
MP
Krug
S K
SK
Ritschel
W
W
Wilmott
R W
RW
D015502:Absorptiometry, Photon; D000293:Adolescent; D001786:Blood Glucose; D001823:Body Composition / Q000187:drug effects; D001827:Body Height / Q000187:drug effects*; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006128:Growth; D006801:Humans; D007328:Insulin / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007408:Intestinal Absorption; D008297:Male; D009748:Nutrition Disorders / Q000097:blood / Q000188:drug therapy*; D012129:Respiratory Function Tests
D001786:Blood Glucose; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I