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Insulin Dynamics Predict Body Mass Index and Z-Score Response to Insulin Suppression or Sensitization Pharmacotherapy in Obese Children

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...

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Published in:The Journal of pediatrics 2006, Vol.148 (1), p.23-29
Main Authors: Lustig, Robert H., Mietus-Snyder, Michele L., Bacchetti, Peter, Lazar, Ann A., Velasquez-Mieyer, Pedro A., Christensen, Michael L.
Format: Article
Language:English
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Summary: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 μg/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.
ISSN:0022-3476
1097-6833
DOI:10.1016/j.jpeds.2005.08.075