Within-subject variability of measures of beta cell function derived from a 2 h OGTT: implications for research studies.
OBJECTIVE
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
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.
Utzschneider
K M
KM
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System (151), Seattle, WA 98108, USA. kutzschn@u.washington.edu
Prigeon
R L
RL
Tong
J
J
Gerchman
F
F
Carr
D B
DB
Zraika
S
S
Udayasankar
J
J
Montgomery
B
B
Mari
A
A
Kahn
S E
SE
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003627:Data Interpretation, Statistical; D003920:Diabetes Mellitus / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000503:physiopathology; D005951:Glucose Tolerance Test / Q000706:statistics & numerical data*; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D015588:Observer Variation; D010186:Pancreatic Function Tests / Q000706:statistics & numerical data*; D012680:Sensitivity and Specificity; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin