Within-subject Variability of Measures of Beta Cell Function Derived From a 2 H OGTT: Implications for Research Studies

Diabetologia. 2007 Dec;50(12):2516-25. doi: 10.1007/s00125-007-0819-5. Epub 2007 Oct 11.

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 (DeltaI(0-30)/DeltaG(0-30)), early C-peptide response (DeltaCP(0-30)/DeltaG(0-30)), incremental AUC insulin to glucose response (incAUC(ins)/incAUC(glu)), integrated insulin secretion response from 0 to 120 min (IS/Glu(0-120)) and indices of beta cell function derived from a mathematical model.

Results: Within-subject variability for DeltaI(0-30)/DeltaG(0-30) (CV 57.1%) was higher than DeltaCP(0-30)/DeltaG(0-30) (CV 34.7%). Measures integrated over the full 120 min of the OGTT, incAUC(ins)/incAUC(glu) (CV 24.9%) and IS/Glu(0-120) (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 DeltaI(0-30)/DeltaG(0-30), 37 for DeltaCP(0-30)/DeltaG(0-30), 21 for incAUC(ins)/incAUC(glu) and 11 for IS/Glu(0-120).

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Data Interpretation, Statistical
  • Diabetes Mellitus / physiopathology
  • Fasting / blood
  • Female
  • Glucose Intolerance / physiopathology
  • Glucose Tolerance Test / statistics & numerical data*
  • Humans
  • Insulin / blood
  • Insulin-Secreting Cells / physiology*
  • Male
  • Middle Aged
  • Models, Theoretical
  • Observer Variation
  • Pancreatic Function Tests / statistics & numerical data*
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Blood Glucose
  • Insulin