beta-Cell function and insulin sensitivity in adolescents from an OGTT

Area of Science:

• Pediatric Endocrinology
• Metabolic Research
• Quantitative Physiology

Background:

• Rising incidence of insulin resistance, obesity, and type 2 diabetes in pediatric populations necessitates accurate assessment tools.
• Current methods for evaluating insulin secretion and action may not be optimal for adolescents during physiological challenges.
• Quantitative indices are crucial for understanding glucose metabolism regulation in youth.

Purpose of the Study:

• To propose and validate a minimal model method for quantifying insulin secretion and action indices in adolescents via an oral glucose-tolerance test (OGTT).
• To assess the accuracy of the minimal model's insulin sensitivity (S(I)) measurement against a reference tracer method.
• To explore the utility of disposition indices derived from the minimal model for evaluating glucose homeostasis.

Main Methods:

• A 7-hour, 21-sample oral glucose-tolerance test (OGTT) was conducted on 11 adolescents.
• C-peptide and glucose data were used to identify a C-peptide minimal model, quantifying beta-cell function indices (static phi(s), dynamic phi(d), total phi).
• Glucose and insulin data were used to identify a glucose minimal model, estimating insulin sensitivity (S(I)), which was compared to a reference tracer method (S(I)(ref)). Disposition indices (DI) were calculated.

Main Results:

• The minimal model accurately quantified beta-cell function indices: phi(s) = 51.35 ± 8.89 x 10⁻⁹ min⁻¹, phi(d) = 1,392 ± 258 x 10⁻⁹, and phi = 82.09 ± 17.70 x 10⁻⁹ min⁻¹.
• Estimated insulin sensitivity (S(I) = 14.19 ± 2.73 x 10⁻⁴ dl/kg·min per μU/mL) was not significantly different from the reference method (S(I)(ref) = 14.96 ± 3.04 x 10⁻⁴ dl/kg·min per μU/mL) and showed strong correlation (r = 0.98, P < 0.0001).
• Disposition indices (DI(s), DI(d), DI) were calculated, and similar results were obtained with a reduced 3-hour, 9-sample protocol.

Conclusions:

• The C-peptide and glucose minimal model, applied to OGTT data, accurately measures quantitative indices of insulin secretion and action in adolescents.
• This method provides a reliable, non-invasive approach to assess insulin sensitivity and beta-cell function, comparable to established tracer methods.
• The minimal model approach using OGTT shows potential for novel insights into adolescent glucose metabolism regulation and evaluating interventions for obesity and diabetes.