Abstract
Purpose of Study: There is controversy about whether the normal pubertal decrease in insulin sensitivity (Si) is compensated by an appropriate increase in β-cell function (BCF), as reflected in their product (disposition index, DI), particularly in African-Americans (AA). It has been postulated that this is because of the predisposition of AA to diabetes. However, the methodological intensity of methods to measure Si has previously precluded simultaneous assessment of glucose tolerance by an oral glucose tolerance test (OGTT) in children. We have circumvented this problem by applying a recently developed oral minimal model (OMM) to frequently sampled OGTT (fsOGTT) data. We assessed glucose-insulin dynamics across puberty in healthy females by the fsOGTT.
Methods used: Healthy female volunteers underwent an fsOGTT, with assays of insulin, C-peptide, and glucose, as well as baseline plasma insulin-like growth factor-I (IGF-I). Those with normal OGTT (6 yr to 50 yr, n=52) were 42% AA, 42% Caucasian (C) and were grouped by pubertal stage (prepubertal, early pubertal, postmenarcheal < 18 years, and adult). Body mass index percentile was similar among stages, averaging 63rd-85th percentile. Si, BCF, and DI were derived from the OMM; other indices of Si and BCF were also computed. Statistical analysis was by analysis of variance and covariance, and Kruskall-Wallis tests, with post-hoc Dunn's tests.
Summary of results: Si by OMM fell from 22.8 ± 3.1 (SEM) dL kg-1m/mU/mL 10-4 prepubertally to 8.3 ± 2.2 post-menarcheally (p≤0.01) and then recovered to 12.0 ± 4.4 in adults. Several other indices showed these changes, but others were less sensitive (e.g., HOMA-IS). Neither BCF (by OMM or insulin response to glucose) nor glucose changed significantly with stage. Consequently, DI by OMM followed the Si pattern of transient pubertal decrease (p<0.02). The IGF-I pattern was reciprocal (p<0.001).
Conclusions: We confirm that DI declines in parallel to Si during normal puberty. Additionally, we show in an ethnically diverse population that this occurs in the absence of glucose intolerance and does not persist into adulthood. This implies that insulin-independent glucose metabolism increases during normal puberty. This coincides with the pubertal peak in IGF-I levels. We suggest that the fall in Si induced by the known pubertal rise in GH secretion is countered by the insulin-sparing effect of the concomitant rise in IGF-I.
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Littlejohn, E., Kim, M., Man, C. et al. 12 Both Insulin Sensitivity and Disposition Index Fall During Normal Female Puberty without a Change in Glucose Tolerance.. Pediatr Res 60, 492 (2006). https://doi.org/10.1203/00006450-200610000-00034
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DOI: https://doi.org/10.1203/00006450-200610000-00034