Lustig Robert H, Mietus-Snyder Michele L, Bacchetti Peter, Lazar Ann A, Velasquez-Mieyer Pedro A, Christensen Michael L
Division of Pediatric Endocrinology, Department of Pediatrics, University of California, San Francisco, USA.
J Pediatr. 2006 Jan;148(1):23-9. doi: 10.1016/j.jpeds.2005.08.075.
To assess the use of oral glucose tolerance testing (OGTT) to predict efficacy of insulin sensitization (metformin) or suppression (octreotide) because insulin resistance and insulin hypersecretion may impact pharmacotherapeutic efficacy in obese children.
Forty-three and 24 obese children, with and without central nervous system (CNS) insult, underwent OGTT. Insulin sensitivity was expressed as composite insulin sensitivity index (CISI), and secretion as corrected insulin response (CIRgp). Those without CNS insult received metformin (weight-based dosing) for 6 to 16 months. Those with CNS insult received octreotide SQ 15 microg/kg/d for 6 months. Body mass index (BMI) and z-score responses were modeled using CIRgp and CISI.
Metformin: With CIRgp and CISI = 1, BMI z-score in white children declined by 0.23 over the first 4 months (P < .001), and by 0.14 over the next year (P = .33). Each 2-fold increase in CIRgp or CISI attenuated BMI z-score reduction, but with wide uncertainty (P = .24). Black children exhibited little response. Octreotide: With CIRgp and CISI = 1, BMI z-score decreased by 0.23 in the first 4 months (P = .052). Efficacy was dependent on an interaction between CIRgp and CISI (P = .051).
Efficacy of metformin was predicted by pretreatment insulin resistance. Efficacy of octreotide was predicted by insulin hypersecretion and sensitivity.
评估口服葡萄糖耐量试验（OGTT）在预测胰岛素增敏剂（二甲双胍）或抑制剂（奥曲肽）疗效方面的作用，因为胰岛素抵抗和胰岛素分泌过多可能会影响肥胖儿童的药物治疗效果。
43名有中枢神经系统（CNS）损伤和24名无CNS损伤的肥胖儿童接受了OGTT。胰岛素敏感性以综合胰岛素敏感性指数（CISI）表示，胰岛素分泌以校正胰岛素反应（CIRgp）表示。无CNS损伤的儿童接受二甲双胍（按体重给药）治疗6至16个月。有CNS损伤的儿童接受奥曲肽皮下注射，剂量为15μg/kg/d，持续6个月。使用CIRgp和CISI对体重指数（BMI）和z评分反应进行建模。
二甲双胍：当CIRgp和CISI = 1时，白人儿童的BMI z评分在最初4个月下降了0.23（P <.001），在接下来的一年下降了0.14（P =.33）。CIRgp或CISI每增加2倍，BMI z评分降低幅度就会减弱，但存在很大的不确定性（P =.24）。黑人儿童几乎没有反应。奥曲肽：当CIRgp和CISI = 1时，BMI z评分在最初4个月下降了0.23（P =.052）。疗效取决于CIRgp和CISI之间的相互作用（P =.051）。
二甲双胍的疗效可通过治疗前的胰岛素抵抗来预测。奥曲肽的疗效可通过胰岛素分泌过多和敏感性来预测。
