Population analysis of ethnicity and first-phase insulin release.
OBJECTIVE
A mechanistic, physiologically-based pharmacokinetic (PK/PD) model was developed to describe the biphasic insulin release and evaluate the racial effects on the glucose-insulin kinetics in response to intravenous glucose.


METHODS
Fifteen African-American and 18 Caucasian children and adolescents between 8 and 18 years of age were enrolled in the study. Intravenous bolus of glucose (250 mg/kg) was administered and blood samples collected at frequent intervals for three hours following the glucose injection. A nonlinear mixed-effect population kinetic analysis with covariate structure was performed using Monolix.


RESULTS
A significantly higher initial insulin secretion from a readily releasable pool, which is responsible for the first-phase insulin secretion, was detected in African-Americans compared to Caucasians (p<0.05).


CONCLUSIONS
The proposed kinetic model is able to describe the glucose-stimulated insulin response, account for the first-phase insulin release and identify a racially-based pharmacokinetic difference in insulin's biphasic secretion behavior. It is hypothesized that the first-phase insulin component may play an important role in the development of type 2 diabetes. The proposed mechanistic model provides a quantitative analysis of the biphasic insulin release that may be useful in the early detection of diabetes.
Xie
Lanyi
L
Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States.
Hoffman
Robert P
RP
Veng-Pedersen
Peter
P
D000293:Adolescent; D001741:Black or African American; D002648:Child; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D044465:White People
D007328:Insulin; D005947:Glucose