First test effect in intravenous glucose tolerance testing

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.

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.

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.

A statistically significant first test effect occurs during the IVGTT attributable to variations in insulin secretion rather than hepatic uptake.