Hyperinsulinism, neonatal obesity and placental immaturity in infants born to women with one abnormal glucose tolerance test value.

Abstract

Several groups have reported a risk of fetal macrosomia in pregnancies with maternal glucose intolerance which is intermediate between gestational diabetes (GDM) and normal glucose tolerance. The present study was designed to determine whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and placental villous immaturity. 325 women with risk factors for GDM underwent a 75 g OGTT interpreted according to the O'Sullivan criteria. All women who met the criteria for GDM were managed with diet therapy. Insulin therapy was added for women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile. Patients not meeting the GDM criteria were managed without special intervention. Primary outcome variables were measures of neonatal weight and skinfold thickness, fetal and neonatal insulin and glucose concentration, and placental villous maturation. Outcome parameters were compared among three groups: pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1 abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value in the OGTT was different from those with normal OGTT. Regarding fetal growth, rates of LGA were approximately twice as high in groups with one abnormal value and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1 and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control only). Regarding fetal hyperinsulinism, AFI concentrations were similar in control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p < 0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1 abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1 abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in the one abnormal value than in the control group (49% vs 34% of infants) and intermediate in the GDM group (40%). Severe placental villous immaturity was more than twice as frequent in the 1 abnormal value group compared to controls (24% vs 9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs controls). Pregnancies with glucose intolerance below the thresholds for diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism, postpartum hypoglycemia and placental immaturity. These findings indicate the continuum of risk for fetal morbidity associated with increasing maternal glucose intolerance in pregnancy.