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 β-cell function: static Φ s and dynamic Φ d responsivity to glucose from which total responsivity Φ 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 β-cell function were Φ s = 51.35 ± 8.89 × 10 -9 min -1 , Φ d = 1,392 ± 258 × 10 -9 , and Φ = 82.09 ± 17.70 × 10 -9 min -1 . Insulin sensitivity was S I = 14.19 ± 2.73 × 10 -4 , not significantly different from S I ref = 14.96 ± 3.04 × 10 -4 dl/kg . min per μU/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 × 10 -14 dl/kg/min 2 per pmol/l, DI d = 33,178 ± 10,720 × 10 -14 dl/kg/min per pmol/l, DI = 1,844 ± 522 × 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.

Effects of a hypercaloric diet on β‐cell responsivity in lean healthy men

“…To relate changes in insulin secretion to changes in insulin sensitivity, total, dynamic and static disposition indexes (DIs) were calculated. The DIs were calculated according to earlier published equations . DI calculation, as depicted below, is based on multiplying the individual indexes of insulin secretion by insulin sensitivity.…”

The Oral Minimal Model Method

“…For instance, the battery of oral glucose, C-peptide, and insulin models has been used to study the effect of age and sex on glucose metabolism (8), the effect of antiaging drugs (35), the influence of ethnicity (36), S I and β-cell function in nondiabetic (37) and obese (38) adolescents and children (39), the pathogenesis of prediabetes (17,40,41) and type 2 diabetes (1,42), the diurnal pattern of insulin action and secretion in healthy (43) and type 1 diabetic (44) subjects, the mechanism of insulin resistance in pregnancy (45), the effect of DPP4 inhibitors on insulin secretion (46), and the effect of a bile acid sequestrant on insulin secretion and action (47). These models also can be used to quantitatively measure changes in insulin secretion, insulin action, glucose effectiveness, and hepatic insulin extraction in individuals with prediabetes who do versus those who do not progress to overt diabetes.…”

Diabetes: Models, Signals, and Control

“…However, it may be helpful for the reader to refer to specific instances where an answer to a diabetes-related question has been provided by a systematic use of models. For instance, the battery of oral glucose, C-peptide, and insulin models have been used in studying: the effect of age and gender on glucose metabolism [59]; the effect of anti-aging drugs [110]; the influence of ethnicity [111]; insulin sensitivity and beta-cell function in nondiabetic [112] and obese [113] adolescents; the pathogenesis of prediabetes [114]–[116] and type 2 diabetes [117], [118]. …”