Growth-differentiation-factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function.

Abstract

Growth-differentiation-factor 15 (GDF15) has been suggested to improve or protect beta cell function. During pregnancy, beta cell numbers and function increase to overcome the natural rise in insulin resistance during gestation. In this study, we longitudinally measured serum GDF15 levels during and after pregnancy in women of normal weight (NW) and in women with obesity (OB) and explored associations between GDF15 and changes in beta cell function by homeostatic model assessment (HOMA). The cohort participants were 38 NW (BMI 22.3±1.7) and 35 OB (BMI 35.8±4.2). Blood was sampled and body composition measured at each trimester (T1, T2, and T3) and at 6, 12 and 18months postpartum. Fasting glucose, insulin and GDF15 were measured, and HOMA for insulin resistance (HOMA-IR) and beta cell function (HOMA-B) determined. GDF15 levels increased significantly each trimester and were ~200-fold higher at T3 than in the nonpregnant postpartum state. GDF15 was higher in NW than OB during pregnancy, but was reversed after pregnancy with a significant interaction effect. GDF15 correlated inversely with BMI and fat-free mass at T3. Low GDF15 was associated with lower incidence of nausea and with carrying a male foetus. The pregnancy induced increase in GDF15 associated with increased HOMA-B in OB and with reduced fasting glucose in all women. Large gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy-induced insulin resistance.