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Insulin dynamics predict body mass index and z-score response to insulin suppression or sensitization pharmacotherapy in obese children

By January 1, 2006September 24th, 2020No Comments


The Journal of Pediatrics

Robert H Lustig 1 ,
Michele L Mietus-Snyder,
Peter Bacchetti,
Ann A Lazar,
Pedro A Velasquez-Mieyer,
Michael L Christensen

Objective: 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.
Study design: 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.
Results: 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). Conclusions: Efficacy of metformin was predicted by pretreatment insulin resistance. Efficacy of octreotide was predicted by insulin hypersecretion and sensitivity.


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