Hamilton Jill K, Conwell Louise S, Syme Catriona, Ahmet Alexandra, Jeffery Allison, Daneman Denis
Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada M5G 1X8.
Int J Pediatr Endocrinol. 2011;2011(1):417949. doi: 10.1155/2011/417949. Epub 2011 Mar 22.
Objective. To assess the effect of combined diazoxide-metformin therapy in obese adolescents treated for craniopharyngioma. Design. A prospective open-label 6-month pilot treatment trial in 9 obese subjects with craniopharyngioma. Diazoxide (2 mg/kg divided b.i.d., maximum 200 mg/day) and metformin (1000 mg b.i.d.). Whole body insulin sensitivity index (WBISI) and area-under-the-curve insulin (AUC(ins)) were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age 15.4 ± 2.9 years, weight 99.7 ± 26.3 kg, BMI 35.5 ± 5.6 kg/m(2), and BMI SDS 2.3 ± 0.3. Two were withdrawn due to vomiting and peripheral edema. Of participants completing the study, the mean ± SD weight gain, BMI, and BMI SDS during the 6 months were reduced compared to the 6 months prestudy (+1.2 ± 5.9 versus +9.5 ± 2.7 kg, P = .004; -0.3 ± 2.3 versus +2.2 ± 1.5 kg/m(2), P = .04; -0.04 ± 0.15 versus +0.11 ± 0.08, P = .021, resp.). AUC(ins) correlated with weight loss (r = 0.82, P = .02) and BMI decrease (r = 0.96, P = .009). Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUC(ins) at study commencement predicted effectiveness of the treatment.
目的。评估二氮嗪联合二甲双胍治疗颅咽管瘤肥胖青少年的效果。设计。对9名患有颅咽管瘤的肥胖受试者进行为期6个月的前瞻性开放标签试验性治疗。二氮嗪（2mg/kg，每日两次，最大剂量200mg/天）和二甲双胍（每日两次，每次1000mg）。计算全身胰岛素敏感性指数（WBISI）和曲线下胰岛素面积（AUC(ins)）。结果。7名受试者完成试验：4名男性/3名女性，平均±标准差年龄15.4±2.9岁，体重99.7±26.3kg，体重指数（BMI）35.5±5.6kg/m²，BMI标准差评分（BMI SDS）2.3±0.3。2名受试者因呕吐和外周水肿退出。完成研究的参与者在6个月期间的平均±标准差体重增加、BMI和BMI SDS较研究前6个月有所降低（分别为+1.2±5.9与+9.5±2.7kg，P = 0.004；-0.3±2.3与+2.2±1.5kg/m²，P = 0.04；-0.04±0.15与+0.11±0.08，P = 0.021）。AUC(ins)与体重减轻（r = 0.82，P = 0.02）和BMI降低（r = 0.96，P = 0.009）相关。结论。二氮嗪联合二甲双胍治疗与下丘脑性肥胖患者体重增加减少有关。研究开始时的AUC(ins)可预测治疗效果。
