Within-subject variability of measures of beta cell function derived from a 2 h OGTT: Implications for research studies

Abstract

Aims/hypothesis: Knowledge of the within-subject variability of a parameter is required to properly design and calculate sample sizes for longitudinal studies. We sought to determine the day-to-day variability of measures of beta cell function derived from an OGTT. Methods: Thirty-seven adults (13 with normal glucose tolerance, ten with impaired glucose tolerance, 14 with type 2 diabetes) underwent a standard 2 h 75 g OGTT on two separate days (median time between tests, 7 days; range, 5-14). From these data, the reproducibility of several indices of beta cell function were determined: insulinogenic index (ΔI0-30/ΔG0-30), early C-peptide response (ΔCP0-30/ΔG0-30), incremental AUC insulin to glucose response (incAUCins/incAUCglu), integrated insulin secretion response from 0 to 120 min (IS/Glu0-120) and indices of beta cell function derived from a mathematical model. Results: Within-subject variability for ΔI0-30/ΔG0-30 (CV 57.1%) was higher than ΔCP0-30/ΔG0-30 (CV 34.7%). Measures integrated over the full 120 min of the OGTT, incAUC ins/incAUCglu (CV 24.9%) and IS/Glu0-120 (CV 17.4%), demonstrated less variability. The mathematical model-derived measures of beta cell glucose sensitivity (CV 20.3%) and potentiation (CV 33.0%) showed moderate variability. The impact of the different measures' variability on sample size (30% change from baseline) is demonstrated by calculated sample sizes of 89 for ΔI0-30/ΔG0-30, 37 for ΔCP0-30/ΔG0-30, 21 for incAUC ins/incAUCglu and 11 for IS/Glu0-120. Conclusions/interpretation: Some OGTT-derived indices of beta cell function, in particular the insulinogenic index, demonstrate high within-subject variability. Integrated measures that utilise multiple time points and measures that use C-peptide show less variability and may lead to a reduced sample size requirement. © 2007 Springer-Verlag.