Pharmacokinetic/pharmacodynamic insulin‐glucose analysis for differentiation of beta‐cell function: an 18 month follow‐up study in pre‐pubertal lean and obese children

Abstract

The objective of this study was to analyse the PK/PD of the insulin-glucose physiology for glucose stimulated insulin secretion from beta-cells between lean and obese pre-pubertal children in an 18 month study. The subjects were divided into two groups of six children according to their body mass index (BMI). Each subject was assessed on four occasions: on admission and at 6, 12 and 18 month follow-ups. Each time, 23 blood samples were obtained from the subjects according to the frequently sampled intravenous glucose tolerance test involving a bolus of 250 mg/kg dextrose. For the obese group, a significant difference (p <0.05) was found in the rate constant for the first phase secretion of insulin between the time of admission (1.73 +/- 0.372 min(-1)) and the 18 month follow-up (3.08 +/- 0.391 min(-1)). Additionally, the lean vs obese group comparisons showed a higher first phase insulin secretion rate constant (p <0.05) in the obese group on admission (1.73 +/- 0.372 vs 1.29 +/- 0.278 min(-1)), 6 months (1.96 +/- 0.317 vs 1.32 +/- 0.444 min(-1)), 12 months (2.33 +/- 0.621 vs 1.57 +/- 0.435 min(-1)) and 18 months (3.08 +/- 0.391 vs 1.83 +/- 0.587 min(-1)). The proposed PK/PD model for the insulin secretion from beta-cells is able to identify kinetic differences in first phase insulin secretion between lean and obese non-diabetic pre-pubertal children in this 18 month follow-up study.