Insulin Sensitivity and Insulin Secretion Differentially Affect Birthweight and Postpartum Glucose

Abstract Introduction/objective We tested whether early pregnancy insulin resistance and insulin deficiency are associated with infant birthweight percentile and postpartum glucose in women with diabetes risk factors. Methods This was a secondary analysis of data from the prospective Study of Pregnancy Regulation of Insulin and Glucose (SPRING). Participants were enrolled at 7-14 weeks’ gestation and underwent a 2-hour oral glucose tolerance test (OGTT) with hourly glucose and insulin measures. Exposures were first-trimester (7-14 weeks’ gestation) log-transformed insulin resistance and insulin secretory response, determined using the Matsuda index and Stumvoll first-phase estimate. Primary outcomes were birthweight percentile and 2-hour OGTT glucose at 6-24 weeks postpartum. Secondary outcomes included fasting, 30-min, and 1-hour OGTT glucose postpartum. We used covariate-adjusted linear regression models to quantify associations between standardized exposures and outcomes. Results Among 150 participants, greater first-trimester insulin resistance was associated with higher birthweight percentile (adjusted β: 5.11%, 95% CI: 0.04, 10.18 per 1 SD decrease in log Matsuda index), but not with postpartum glucose. Lower first-trimester insulin secretory response was not associated with birthweight percentile, but it was associated with higher postpartum 2-hour OGTT glucose (adjusted β: 13.96 mg/dL, 95% CI: 7.24, 20.69 per 1 SD decrease in log Stumvoll estimate), as well as glucose at the fasting, 30-min, and 1-hour post-OGTT time points postpartum. Conclusions Insulin resistance and insulin deficiency in the first trimester are differentially associated with maternal and fetal outcomes. Assessing the underlying mechanisms of hyperglycemia in pregnancy may enable more personalized risk assessment.