OBJECTIVE -To estimate the impact of type 1 diabetes during pregnancy on transgenerational genetically caused and/or fuel-mediated amplification of types 1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin levels. RESEARCH DESIGN AND METHODS-A total of 75 white offspring of type 1 diabetic mothers and 49 control subjects of similar age and pubertal stage were examined at 5-15 years of age. All offspring had an oral glucose tolerance test. Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after loading. Lipids and autoimmune antibodies were measured in fasting plasma.RESULTS -Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%) had autoimmune antibodies. Offspring of diabetic mothers had significantly higher BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and insulin resistance than control subjects. With the exception of cholesterol, these values were significantly elevated in offspring who had elevated amniotic fluid insulin levels (Ͼ8 µU/ml, Ͼ48 pmol/l) during pregnancy compared with normoinsulinemic offspring and control subjects.CONCLUSIONS -Offspring of type 1 diabetic mothers have an increased risk for diabetes later in life. The relative risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2 diabetes-associated risk factors, such as high BMI; elevated glucose, insulin, and C-peptide levels; and insulin resistance, are related to the fetal metabolic experience in utero, as reflected by amniotic fluid insulin concentration.

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Insulin binding to trophoblast plasma membranes and the placental glycogen content were measured in twelve healthy women, in eleven well-controlled gestational diabetic women who were treated either with diet alone (n = 4) or with insulin (n = 7) and in 18 women with well-controlled overt diabetes mellitus (six White B; four White C; eight White D). The competitive binding assay was carried out with 22 concentrations of unlabelled insulin. Binding data were analysed by a non-linear direct model fitting procedure assuming one non-cooperative binding site. Maximum specific binding was unchanged in the total collective of gestational diabetic women, but was decreased by 30% in those treated with diet (6.2 +/- 2.2%) and increased by 90% in insulin-treated women (16.4 +/- 10.2%) as compared to the control subjects (8.7 +/- 2.5%). The diet-treated women had only 40% as many and those treated with insulin had more than twice as many receptors compared to control subjects on a per mg protein basis and if expressed per total placenta. In patients with overt diabetes mellitus maximum specific binding (18.5 +/- 10.6%) was higher (p less than 0.05) due to more receptors compared to control subjects but was similar to the insulin-treated gestational diabetic patients. Maximum specific binding and receptor concentrations did not correlate linearly with maternal plasma insulin levels. Receptor affinities were virtually similar in all groups (1.8 x 10(9) l/mol). The placental glycogen content was reduced (p less than 0.05) to about 80% of that of control subjects in the diet-treated collective, whereas it was unchanged compared to control subjects in the insulin-treated gestational diabetic women despite a 40% increase (p less than 0.001) of the maternal-to-cord serum glucose ratio. In overt diabetic patients the maternal-to-cord serum glucose ratio and the placental glycogen content were higher (p less than 0.05) than in the control subjects. We conclude that trophoblast plasma membranes from gestational diabetic women treated with diet alone express less and those from women treated with insulin express more insulin receptors than those from a healthy control group in vitro. These differences could not have been disclosed without consideration of the mode of treatment. Trophoblast plasma membranes from overt diabetic women have more insulin receptors than those from healthy control subjects.

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Objective To define the normal ranges of umbilical cord blood oxygen saturation (SaO,) and acid-base status at birth and to evaluate the effect of gestational age on cord blood values in vigorous newborn infants following spontaneous vaginal birth from a vertex position.Design Prospective study.Setting Department of Obstetrics and Gynaecology, University of Graz, Austria.Sample Cord blood samples from 1281 vigorous newborn infants.Methods Cord blood sampling was performed following on newborn infants following spontaneous vaginal birth in a vertex position. SaO, was measured directly by a spectrophotometer and pH, base excess, pC0, and PO, by a pH/blood-gas analyser. Infants with a 5-minute Apgar score 2 7 were considered vigorous. Subgroups were classified according to the gestational age: preterm, term and postterm (< 37,3742 and > 42 weeks, respectively). ResultsThe median umbilical artery SaO, was 24.3% and the 2.5th centile was as low as 2.7%. The median umbilical artery values were pH = 7-25, base excess = -4.3 mmol/L and PO, = 16 mmHg. The 2.5th centiles were 7.08, -1 1.1 mmol/L and 5 mmHg, respectively. The median umbilical artery pC0, was 50 mmHg and the 97.5th centile was 75 mmHg. The mean umbilical artery and vein SaO, values were not significantly influenced by gestational age. The umbilical artery SaO, and base excess values were strongly skewed. The mean umbilical artery pH values in preterm infants were higher than in other subgroups. The mean umbilical artery and vein base excess values were lower in post-term newborn infants than in other subgroups.Conclusions The physiological range of oxygen saturation in umbilical cord of vigorous newborn infants at birth is wide and skewed. In contrast to pH and base excess, umbilical cord blood oxygen saturation is not influenced significantly by gestational age at birth.