Fetal Exposure to Altered Amniotic Fluid Glucose, Insulin, and Insulin-Like Growth Factor–Binding Protein 1 Occurs Before Screening for Gestational Diabetes Mellitus

OBJECTIVE: We explored the possibility that perturbations in amniotic fluid glucose, insulin, and insulin-like growth factor–binding protein 1(IGFBP1) and/or metabolic acids exist before routine screening for GDM. RESEARCH DESIGN AND METHODS: We selected consenting mother-infant pairs (n = 408) who met our inclusion criteria (singleton pregnancy, no genetic abnormalities, and no preexisting diabetes) and for whom sufficient amniotic fluid and appropriate medical information were available. We compared birth outcomes and second trimester amniotic fluid glucose, insulin, IGFBP1 concentrations, and amniotic fluid lactic, β-hydroxybutyric, and uric acids of mothers with gestational diabetes mellitus (GDM) (n = 52) with those of mothers with no diagnosis of GDM at >24 weeks (n = 356). RESULTS: Higher amniotic fluid glucose, lactic acid, uric acid, and insulin and lower IGFBP1 concentrations were present by 15.1 ± 0.1 weeks in mothers in whom GDM was subsequently diagnosed. However, logistic regression showed that second trimester amniotic fluid glucose, but not insulin, IGFBP1, or metabolic acids was associated with an increased odds ratio (1.2 [95% CI 1.052–1.338]) for diagnosis of GDM at 24–28 weeks. In addition, probability contour maps that accounted for nonlinear relationships among the dynamically changing amniotic fluid constituents showed an increased risk for GDM with elevated second trimester amniotic fluid glucose in combination with either elevated amniotic fluid insulin or low amniotic fluid IGFBP1 CONCLUSIONS: Fetuses are exposed to increased amniotic fluid glucose before 15 weeks of gestation, suggesting that metabolic perturbations are underway before diagnosis and that earlier screening and intervention may be warranted.