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


METHODS
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.
Lustig
Robert H
RH
Division of Pediatric Endocrinology, Department of Pediatrics, University of California, San Francisco, USA. rlustig@peds.ucsf.edu
Mietus-Snyder
Michele L
ML
Bacchetti
Peter
P
Lazar
Ann A
AA
Velasquez-Mieyer
Pedro A
PA
Christensen
Michael L
ML
D000293:Adolescent; D044383:Black People; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002493:Central Nervous System Diseases / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007223:Infant; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015282:Octreotide / Q000627:therapeutic use; D011863:Radioimmunoassay; D044465:White People
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D015282:Octreotide