Pharmacokinetic/pharmacodynamic differentiation of pancreatic responsiveness in obese and lean children

Objective. To determine the feasibility of differentiating the glucose-stimulated plasma insulin response between lean and obese children using a new PK/PD model that specifically considers the insulin-glucose physiology of beta cells. Methods. Twenty four blood samples obtained after an intravenous bolus administration of glucose (250 mg/kg) were analysed for glucose and insulin concentrations in a group of six obese children, age 10.8 ± 12.9 years (mean ± CV%); BMI 26.7 ± 27.8 kg/m², and six lean children, age 10.3 ± 10.5, BMI 15.7 ± 10.8. Results. A PK/PD analysis of insulin concentration was performed and significant differences (p<0.05) were determined from the parameters of our model in first and second phase insulin secretion between obese vs lean subjects. The estimated proinsulin formation rate constant was significantly higher in the obese group compared with the lean group (1.60 ± 43.1 vs 0.378 ± 40.9 min^-1). The half-life of insulin in plasma was calculated to be 6.36 ± 39.9 min for the obese group and 6.84 ± 30.1 min for the lean group. The new model showed good agreement with data for both the obese group (r = 0.962 ± 4.56) and for the lean group (r = 0.980 ± 1.93). Conclusion. The proposed model is able to differentiate between lean and obese prepubertal children via specific kinetic parameters relating to beta-cell function.