Bucuvalas J C, Chernausek S D, Alfaro M P, Krug S K, Ritschel W, Wilmott R W
Division of Gastroenterology and Nutrition, Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A.
J Pediatr Gastroenterol Nutr. 2001 Nov;33(5):576-81. doi: 10.1097/00005176-200111000-00012.
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.
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.
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.
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.
营养不良在囊性纤维化（CF）患者中很常见，且对生存产生不利影响。由于胰岛素样生长因子-1（IGF-1）在碳水化合物代谢方面具有胰岛素样作用且能促进生长，作者推测使用IGF-1会提高CF患儿的线性生长速率并降低胰岛素需求量。
作者采用双盲安慰剂对照交叉设计。7名9.6至13岁的青春期前儿童（5名男孩和2名女孩）接受了6个月的安慰剂或IGF-1治疗。经过6个月的洗脱期后，患者接受替代治疗6个月。主要结局指标是线性生长速率。次要结局指标包括体重指数的变化、通过双能X线吸收法测定的身体成分、用力呼气量（FEV₁）以及血糖/胰岛素比值。
基线时平均身高z评分为-1.5±0.8。入组时，平均血清IGF-1水平为124±25 ng/mL（正常范围为110 - 771 ng/mL）。治疗后，所有患者的平均血清IGF-1水平增加了两倍至三倍。IGF-1的半衰期为10.3小时。与安慰剂相比，我们观察到在使用IGF-1治疗期间，线性生长速率、体重增加、瘦体重增加速率或平均FEV₁均无显著差异。与安慰剂相比，IGF-1治疗使胰岛素敏感性的间接指标血糖/胰岛素比值显著升高（P < 0.02）。未检测到与IGF-1相关的不良事件。
对青春期前CF患儿进行6个月的IGF-1治疗并未促进线性生长。然而，IGF-1治疗在不改变血糖水平的情况下提高了血糖/胰岛素比值，提示胰岛素敏感性增加。
