Early Pregnancy-Associated Plasma Protein A Concentrations Are Associated With Third Trimester Insulin Sensitivity

CONTEXT: First or early second trimester pregnancy-associated plasma protein A (PAPP-A) concentrations have previously been shown to be lower in women who subsequently develop gestational diabetes mellitus (GDM) and gestational hypertension. OBJECTIVE: We therefore sought to investigate why circulating PAPP-A concentrations are related to the subsequent risk of GDM and gestational hypertension. PATIENTS, DESIGN, AND SETTING: We measured serum PAPP-A concentrations around week 15 of pregnancy and related these to indices derived from week 28 oral glucose tolerance tests and blood pressures across pregnancy in the Cambridge Baby Growth Study cohort. RESULTS: Increased PAPP-A concentrations were associated with reduced GDM risk [odds ratio 0.623 (0.453, 0.856), P = 3.5 × 10(−3), n = 777] and reduced mean arterial blood pressures (β = −0.202 to −0.177, P = 1.7 to 6.9 × 10(−3), n = 347 to 355). They were also negatively associated with week 28 fasting (β = −0.149, P = 6.6 × 10(−4), n = 777) and 60-minute (β = −0.188, P = 1.5 × 10(−5), n = 777) oral glucose tolerance test glucose concentrations. These associations were underpinned by the strong associations between increased week 15 PAPP-A concentrations and decreased week 28 insulin resistance (homeostasis model assessment of insulin resistance: β = −0.319, P = 1.7 × 10(−13), n = 768), as well as increased insulin secretion relative to insulin sensitivity (insulin disposition index: β = 0.202, P = 6.5 × 10(−6), n = 731). CONCLUSIONS: These results suggest that links between PAPP-A concentrations in early pregnancy and subsequent glucose concentrations and blood pressures may be mediated by changes in insulin sensitivity (and secretion).