Background: We previously showed that insulin response to an IV glucose load increases in early pregnancy, independent of changes in insulin sensitivity. It is unknown whether oral glucose tolerance test (OGTT)-based measures of insulin secretory response (ISR) capture the same phenomenon.

Methods: This is a secondary analysis of a longitudinal study. Participants (N=31) were studied pre-pregnancy and in early (12-14 wks) and late (34-36 wks) gestation. On separate days, after overnight fasts, an OGTT (75g pre-pregnancy/100g in pregnancy) and an hyperinsulinemic-euglycemic clamp were performed. We calculated Insulinogenic index (IGI), Corrected insulin response (CIR), insulin/glucose area under the curve (AUCins/AUCglu), and Stumvoll 1st Phase Estimate (Stumvoll) from OGTT insulin and glucose levels. Linear mixed effects models examined ISR in early as compared to pre- and late pregnancy; we adjusted p-values for 2 comparisons. Adjusted models included insulin sensitivity, measured with the clamp, as a time-dependent covariate.

Results: IGI (adjusted mean ± SEM) increased between pre- and early pregnancy (1.25 ± 0.13 vs. 1.52 ± 0.15, P<0.05) and remained stable between early and late pregnancy (1.41 ± 0.14, P=0.42). Findings did not change after adjustment for insulin sensitivity (pre:1.29 ± 0.13 vs. early: 1.59 ± 0.16, P=0.03; early vs. late: 1.31 ± 0.16, P=0.32). Changes in CIR were similar. AUCins/AUCglu increased from pre- to early pregnancy (0.47 ± 0.05 vs. 0.55 ± 0.05 P=0.03) and increased further from early to late pregnancy (0.79 ± 0.07, P<0.01). The increase in AUCins/AUCglu between pre- and early pregnancy was independent of changes in insulin sensitivity (0.50 ± 0.04 vs. 0.66 ± 0.05, P<0.01), but the increase between early and late pregnancy (0.65 ± 0.07) was not apparent after adjusting for insulin sensitivity (P>0.99). The results for Stumvoll were similar.

Conclusion: OGTT-based ISR indices capture an insulin sensitivity-independent augmentation of insulin secretion in early pregnancy.


C.E. Powe: None. J.J. Locascio: None. P. Catalano: None.


National Institutes of Health (K23DK113218); Robert Wood Johnson Foundation; Harold Amos Medical Faculty Development Award

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