First test effect in intravenous glucose tolerance testing

Aims Intravenous glucose tolerance testing ( IVGTT ) is a common test of β‐cell function in which a glucose load is administered and insulin and/or C‐peptide responses are monitored. Since the first IVGTT may be more stressful and stress may alter β‐cell secretion or hepatic insulin extraction, we asked whether there was a first test effect. Methods Insulin and C‐peptide responses were compared from two sequential IVGTTs performed within 6 months during staging for the Diabetes Prevention Trial‐Type 1 ( DPT ‐1) in 368 people at high risk for type 1 diabetes. Insulin data (1+3 min) were used because the first phase insulin response (and peak insulin concentration) occurs within this time frame. Areas under the curve ( AUC ) calculations represent early insulin or C‐peptide responses from 0 through 10 min post‐glucose challenge. Results More than half of all subjects were found to have first test values lower than the second. This was true for all measures of both insulin and C‐peptide but the frequency was significantly different only for insulin measures corrected for basal and for insulin AUC (p < 0.05). However, for subjects (n = 99) whose 1+3 min insulin response was <10th percentile on the first test, there was a significant increase on the second test (p < 0.05). The C‐peptide: insulin ratio did not change significantly between tests, indicating that differences are due to changes in β‐cell secretion rather than hepatic insulin uptake. Conclusions A statistically significant first test effect occurs during the IVGTT attributable to variations in insulin secretion rather than hepatic uptake.