RESUMEN
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.
Asunto(s)
Índice de Masa Corporal , Resistencia a la Insulina/fisiología , Insulina/sangre , Obesidad/tratamiento farmacológico , Adolescente , Población Negra , Glucemia/análisis , Enfermedades del Sistema Nervioso Central/fisiopatología , Niño , Preescolar , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Lactante , Modelos Lineales , Masculino , Metformina/uso terapéutico , Análisis Multivariante , Obesidad/sangre , Obesidad/fisiopatología , Octreótido/uso terapéutico , Radioinmunoensayo , Población BlancaRESUMEN
OBJECTIVES: To assess insulin dynamics to oral glucose tolerance testing in obese children, denoting individual contributions of insulin hypersecretion versus resistance to racial and etiopathogenetic specificity. STUDY DESIGN: We performed 3-hour oral glucose tolerance testing in 113 nondiabetic obese children (age 13.6 +/- 3.1 years; 41 male, 78 female; 37 black, 41 white; 35 with central nervous system [CNS] insult). The corrected insulin response (CIRgp; measuring beta-cell secretion) and the composite insulin sensitivity index (CISI) were computed and log-transformed, and each was modeled in terms of the other, plus race/etiology, age, sex, body mass index z score, glucose tolerance, pubertal status, and geographic location. RESULTS: A scatterplot of logCIRgp versus logCISI showed that racial and etiopathogenetic groups plotted in different areas. CISI (controlled for CIRgp and other variables) was only 13% lower in blacks than in whites ( P = .32). Conversely, CIRgp (controlled for CISI and other variables) was 49% higher in blacks ( P = .028). CNS insult exhibited a 40% higher CIRgp ( P = .054) and 11% higher CISI ( P = .42) than intact white subjects. CONCLUSIONS: Insulin hypersecretion and resistance are distinct phenomena in childhood obesity. Insulin hypersecretion appears to be the more relevant insulin abnormality both in obese blacks and in CNS insult.