OR08-02 Do OGTT-based Insulin Secretory Response Measures Approximate 1st Phase Insulin Response in Pregnant Women?

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Background: We previously showed that 1st phase insulin response increases dramatically in pregnancy, independent of changes in insulin sensitivity. Measurement of 1st phase insulin response requires the use of hyperglycemic clamps or intravenous glucose tolerance tests (IVGTTs) which are rarely performed in pregnant women. Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy. Methods: In a secondary analysis of a longitudinal study of glucose metabolism in pregnancy, we examined Pearson correlations between OGTT-based insulin secretory response measures and 1st phase insulin response. Forty women were studied pre-pregnancy; 36 returned in early and late pregnancy (12–14 and 34–36 weeks gestation). At each time point, after overnight fasts, an IVGTT and an OGTT were performed on separate days. The 1st phase insulin response was calculated as the incremental area under the curve during the 1st 10 minutes after intravenous administration of a 0.5 g/kg glucose load (or 19g/m2 body surface area if weight >120% ideal body weight). Homeostatic Model Assessment (HOMAB), Insulinogenic index (IGI), Corrected insulin response (CIR), Insulin area under the curve/Glucose area under the curve (AUCins/AUCglu), and the Stumvoll 1st Phase Estimate (Stumvoll) were calculated from insulin and glucose levels measured fasting and 30, 60, 90, 120, and 180 minutes after an oral glucose load (75 grams pre-pregnancy, 100 grams in pregnancy). Results: The best OGTT-based measure for estimation of 1st phase insulin response differed across study timepoints. In early and late pregnancy, AUCins/AUCglu had the strongest correlation with 1st phase insulin response (early: R=0.79, P<0.0001; late: R=0.69, P<0.0001), but was not associated with 1st phase insulin response pre-pregnancy (R=0.32, P=0.08). IGI had the strongest correlation with first phase insulin response pre-pregnancy (R=0.50, P=0.005) and was correlated with 1st phase insulin response in late (R=0.68, P=0.0001), but not early (R=0.36, P=0.07) pregnancy. Stumvoll was the only OGTT-based measure that was significantly correlated with 1st phase insulin response at all timepoints (pre: R=0.44, P=0.01; early: R=0.67, P=0.0001; late: R=0.67, P=0.0001). HOMAB was the weakest correlate of 1st phase insulin response, though the correlation was significant in early pregnancy (pre: R=-0.04, P=0.82; early: R=0.33, P=0.05; late: R=0.18, P=0.28). Conclusion: OGTT-based measures of insulin secretion do not have a consistent relationship with 1st phase insulin response across pre-, early, and late pregnancy. Our findings suggest that Stumvoll can be used in OGTT-based longitudinal studies of insulin secretory response that begin prior to pregnancy and span gestation. For cross-sectional studies in pregnancy, AUCins/AUCglu are the best estimates of 1st phase insulin response.