Fetal hyperinsulinism at 14-20 weeks and subsequent gestational diabetes

To examine the predictive value of amniotic fluid (AF) insulin at 14-20 weeks' gestation for subsequent gestational diabetes and macrosomia in unselected gravidas 35 years or older at time of genetic amniocentesis.

We identified 296 pregnancies through stored AF samples from genetic amniocenteses (collected March 1987 through August 1992) in women meeting the following criteria: age 35 years or older, amniocentesis at 14-20 weeks, performance of a 50-g glucose challenge test, and adequate delivery data.

A modified double-antibody radioimmunoassay reliably measured AF insulin with a detection limit of 0.35 microU/mL. Pregnant women in whom gestational diabetes was later diagnosed had higher median AF insulin levels than women who did not (0.60 versus 0.42 microU/mL, respectively; P = .026). A stepwise logistic regression analysis of gestational age at amniocentesis, maternal second-trimester weight, maternal age, and log AF insulin value on gestational diabetes showed only AF insulin to have a significant association with gestational diabetes (P = .004). Seven of 21 cases of gestational diabetes had AF insulin values exceeding the 95th percentile (1.33 microU/mL) compared with only 14 of 275 women with normal glucose tolerance (P < .001). Amniotic fluid insulin did not predict macrosomia in either nondiabetic or gestational diabetic pregnancies.

Gestational diabetes is associated with increased AF insulin at 14-20 weeks, suggesting augmentation of fetal insulin production in the early fetal period in at least some cases of gestational diabetes.