Determinants of Insulin Sensitivity and Glucose Effectiveness in Early Puberty from the One and Two Compartment Models † 439

Carbohydrate and insulin metabolism change significantly as children enter puberty. Studies using the insulin clamp and the single compartment minimal model have suggested that alterations in body mass and growth hormone action may be responsible. To further elucidate these mechanisms we studied 18 children (age 10.8±1.6 years, mean±SD, 7F, Tanner Stage 1-3) using the stable labelled (6-6 d₂ glucose) frequently sampled 3 hour intravenous glucose tolerance test (250 mg/kg). In all individuals insulin sensitivity (S_I) and glucose effectiveness (S_G) were determined using the one compartment minimal model (1CMM) for both labelled and unlabelled glucose. In 13 subjects the two compartment model (2CMM) was used as well. Standard S_I and S_G from the 1CMM were multiplied by volume of distribution to give results comparable to 2CMM. Every 20 min sampling was performed the night before study to determine mean overnight growth hormone concentration (MGH) and morning blood samples were obtained for measurement of plasma leptin (L), growth hormone binding protein (GHBP), and insulin-like growth factor 1 levels (IGF1). S_I from the unlabelled glucose 1CMM was lower (p<0.01) than S_I from labelled glucose using either the 1CMM or 2CMM which did not differ (table). S_I from the labelled 1CMM and 2CMM were positively related (p<0.02) and both tended to correlate with unlabelled S_I (p<0.1). Unlabelled S_G was greater than labelled S_G from either the 1CMM or 2CMM(p<0.01). The latter was less than the former (p<0.01). S_G from the labelled 1CMM and 2CMM were closely related (p<0.01). Unlabelled S_I, unlabelled S_G and labelled S_I from the 1CMM were not related to any of the measured variables while S_I from 2CMM rose as MGH(p<0.05) increased. Labelled S_G from the 1CMM and 2CMM were negatively related to BMI, GHBP, and IGF1 (p<0.05) and tended to be negatively related to leptin (1CMM, p<0.1; 2CMM, p<0.05) and total body fat (1CMM, p<0.05, 2CMM; p<0.1) Thus, we found no consistent relationship between insulin sensitivity and any of the variables measured. However, glucose effectiveness appears to be determined by peripheral growth homone effect and adiposity. In children the 2CMM and 1CMM used with labelled glucose give similar results for S_I but S_G is lower in the 2CMM.

Table 1 No caption available.