β‐Cell Function and Insulin Sensitivity in Adolescents From an OGTT

Abstract

Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7 h, 21-sample OGTT was performed in 11 adolescents. The C-peptide minimal model was identified on C-peptide and glucose data to quantify indices of beta-cell function: static phi(s) and dynamic phi(d) responsivity to glucose from which total responsivity phi was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, S(I), which was compared to a reference measure, S(I)(ref), provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of beta-cell function were 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). Insulin sensitivity was S(I) = 14.19 +/- 2.73 x 10(-4), not significantly different from S(I)(ref) = 14.96 +/- 3.04 x 10(-4) dl/kg.min per microU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that S(I) can be accurately measured from an oral test. Disposition indices were DI(s) = 1,040 +/- 201 x 10(-14) dl/kg/min(2) per pmol/l, DI(d) = 33,178 +/- 10,720 x 10(-14) dl/kg/min per pmol/l, DI = 1,844 +/- 522 x 10(-14) dl/kg/min(2) per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3 h, 9-sample protocol. OGTT interpreted with C-peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise.