Objective/aim 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). Methods 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 18 months postpartum. Fasting glucose, insulin, and GDF15 were measured, and HOMA for insulin resistance (HOMA-IR) and beta cell function (HOMA-B) determined. Results 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 in T3, but was lower in NW at 18 months after pregnancy. GDF15 correlated inversely with BMI and fat-free mass at T3. Low GDF15 in T1 was associated with lower incidence of nausea and with carrying a male fetus. GDF15 at T2 and T3 and the increases between trimesters associated with increased HOMA-B over the course of pregnancy. Increases in GDF15 either early or late in pregnancy were associated with a reduction in blood glucose between T2 and T3. Conclusion Large gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy-induced insulin resistance.