Gestational diabetes: maternal response to diet and insulin therapy as reflected by glycosylated hemoglobin concentration.

To assess the effects of diet and insulin therapy on pregnancy complicated by gestational diabetes, glycosylated hemoglobin concentration was determined longitudinally in 32 women. Diet was instituted when a diagnosis of gestational diabetes was made and was supplemented with insulin for fasting hyperglycemia. At initial presentation, glycosylated hemoglobin concentration was increased in the 18 women who required insulin compared with the 14 women managed by diet alone (7.1% +/- 0.2% versus 6.2% +/- 0.2%, mean +/- SEM, p less than 0.01). Diet had no effect on glycosylated hemoglobin concentration that remained elevated to 6.1% +/- 0.3% compared with the glycosylated hemoglobin concentration of 5.6% +/- 0.2% for pregnant nondiabetic women (p less than 0.01). Insulin resulted in a decrease in glycosylated hemoglobin concentration within 3 to 5 weeks (p less than 0.05). After 7 to 9 weeks of insulin and diet, the glycosylated hemoglobin concentration in women with fasting hyperglycemia was the same as the glycosylated hemoglobin concentration in women who were managed by diet alone.

Failure of fasting and changes in plasma metabolites to affect spontaneous fluctuations in plasma concentrations of ovine placental lactogen.

The relationships between plasma concentrations of energy substrates and placental lactogen (PL) were investigated in pregnant ewes. In successive hourly samples of plasma PL, concentrations varied by +/- 30% but were not related to general activity or feeding of the ewes or the time of day. Fasting ewes for 72 h did not alter the pattern or the mean PL titres. Insulin-induced acute hypoglycaemia, hyperglycaemia and decreases or increases in free fatty acids (FFA) all failed to alter PL levels significantly during 5-h post-treatment periods. These experiments demonstrate that PL secretion in the ewe fluctuates markedly and is unaffected by changes in plasma glucose FFA concentrations.

Family history of diabetes mellitus and oral glucose tolerance testing criteria.

A review of 185 obstetrical patients, having a family history of diabetes mellitus without medical history of glucose intolerance in the non-pregnant state was conducted. A 3-hour 100-g oral glucose tolerance test was performed on all patients between 20 and 34 weeks of gestation. According to O'Sullivan's criteria for glucose tolerance testing, normal glucose tolerance occurred in 89.7%, while Class A diabetes was identified in 10.3% of patients tested. 3.8% of the study population fulfilled the O'Sullivan criteria for abnormal glucose intolerance and required insulin treatment during pregnancy. The Division of Perinatal Medicine at Duke University has traditionally defined the abnormal glucose tolerance test at glucose values lower than O'Sullivan's internationally accepted criteria. An intermediate group, having abnormal glucose values according to the Duke criteria, was classified as "Carbohydrate Intolerance", comprised 32.4% of the patients tested and were managed identically to O'Sullivan Class A Diabetes. Analysis or perinatal outcome, including macrosomia, birth trauma and neonatal morbidity, revealed that Carbohydrate Intolerance patients fulfilling O'Sullivan criteria, being similar to patients with 'normal' GTT test results. Patients having a family history of diabetes mellitus, appeared as a group to be at increased risk for macrosomia, fetal distress and cesarean delivery, compared with the general population.

Glycosylated hemoglobin: a sensitive indicator of gestational diabetes.

Previous studies suggested that the assessment of hemoglobin A1 (HbA1) concentration was a poor indicator of diabetes in pregnancy. However, HbA1 was measured by ion exchange chromatography, which is subject to spurious alterations. To reevaluate the use of glycosylated hemoglobin concentration (GlyHb) as an indicator of gestational diabetes, 64 women at 10 to 15 weeks' gestation were studied by measuring GlyHb by a specific affinity chromatography assay, and blood glucose concentration was determined one hour post a 50-g oral glucose load. Gestational diabetes developed in 15 women in whom GlyHb (7.4 +/- 0.2%) was greater than in normal pregnant women (5.7 +/- 0.1%, P less than .001). If a GlyHb of 6.3% were chosen as the threshold for diagnostic evaluation for diabetes, only 6.7% of the gestational diabetics would have missed diagnosis. Of normal women, 14.2% would have been subjected to glucose tolerance test. GlyHb elevation was associated with the birth of infants large for gestational age. The assessment of GlyHb by affinity chromatography between 10 and 15 weeks' gestation may be a sensitive predictor of patients who will develop gestational diabetes.

Longitudinal assessment of glycosylated blood protein concentrations in normal pregnancy and gestational diabetes.

Longitudinal changes in glycosylated hemoglobin concentration (GlyHb) and glycosylated serum protein concentration (GSP) in both normal pregnancy and pregnancy complicated by gestational diabetes were determined using affinity chromatography, a method in which nonenzymatically glycosylated proteins are specifically measured. At 7-10 wk gestation, GlyHb in women who developed diabetes (N = 21) was higher than GlyHb in normal women (N = 49) (6.7 +/- 0.2% versus 5.7 +/- 0.2%, respectively, P less than 0.001) and remained elevated throughout gestation. In normal pregnancy, GlyHb decreased to a nadir at 23-26 wk and returned to baseline concentration by 31-34 wk. In gestational diabetes, there was an initial increase in GlyHb to 7.1 +/- 0.5% at 11-14 wk followed by a steady decrease. At 7-10 wk, GSP in women who developed diabetes was not elevated compared with normal concentration, although at 11-14 wk there was significant difference between the two groups (P less than 0.02). In normal women, GSP remained constant throughout gestation. In gestational diabetes, GSP decreased to early pregnancy values (P less than 0.02). Glycosylated blood proteins were elevated in early gestation in women who developed gestational diabetes and may have predictive value in identifying women who will develop diabetes in pregnancy.

Glycosylated hemoglobin concentration in early gestation associated with neonatal outcome.

Previous studies have indicated an association of fetal macrosomia with mild degrees of glucose intolerance in late pregnancy. To determine whether glycosylated hemoglobin concentration in early gestation was related to fetal outcome, 48 pregnant women with normal glucose tolerance and 21 women with gestational diabetes were studied. Glycosylated hemoglobin concentration was determined by a specific aminophenylboronic acid assay, and mean glycosylated hemoglobin concentration was calculated from two or three determinations before 17 weeks' gestation. The incidence of infants large for gestational age was 10% in nondiabetic women with glycosylated hemoglobin concentration of less than 6.0%. With glycosylated hemoglobin concentration of 6.0% to 6.9%, the incidence of infants who were large for gestational age was increased in both nondiabetic women (75%, p less than 0.01) and diabetic women (40%, p less than 0.01). With glycosylated hemoglobin concentration of greater than 7.0%, 36% of infants of diabetic women were large for gestational age. The incidence of hyperbilirubinemia was 2.5% in the infants of nondiabetic women with glycosylated hemoglobin concentration of 6.0%. With glycosylated hemoglobin concentration of 6.0% to 6.9%, hyperbilirubinemia was increased in both the infants of nondiabetic women (38%, p less than 0.01) and diabetic women (30%, p less than 0.01). With glycosylated hemoglobin concentration of greater than 7.0%, hyperbilirubinemia was present in 27% of infants of diabetic mothers. The current study suggests that glycosylated hemoglobin concentration elevation in early gestation is associated with perinatal morbidity.

The correlations of glycosylated serum protein and glycosylated hemoglobin concentrations with blood glucose in diabetic pregnancy.

The usefulness of concentrations of glycosylated serum protein and glycosylated hemoglobin in monitoring glycemic control during pregnancy complicated by diabetes was evaluated by correlation of these parameters with fasting and 2-hour postprandial glucose concentrations of the previous 7 days. Glycosylated serum protein correlated with both fasting (r = 0.798, p less than 0.01, n = 71) and postprandial (r = 0.846, p less than 0.01, n = 69) blood glucose concentrations. Glycosylated hemoglobin also correlated with fasting (r = 0.571, p less than 0.01, n = 71) and postprandial (r = 0.510, p less than 0.01, n = 74) blood glucose concentrations. Monitoring glycosylated serum protein during pregnancy complicated by diabetes is clinically feasible and allows frequent reappraisal of diabetic control.

Differential effects of ornithine on placental lactogen and growth hormone secretion in the pregnant ewe and fetus.

The intravenous infusion of ornithine (0.5-0.9 g/kg) into five fetal sheep of 116-141 days gestation caused no significant change in concentrations of fetal plasma placental lactogen (PL) or GH as determined by specific homologous radioimmunoassays. In contrast, the intravenous infusion of ornithine (0.3-0.5 g/kg) into three of the ewes caused a 144.5 +/- 74.7 (S.E.M.)% increase in maternal plasma PL concentrations and a 255.2 +/- 55.0% increase in maternal GH concentrations. Fetal PL concentrations remained unchanged depsite the large increase in maternal PL concentrations. This study, which indicates a differential effect of ornithine on PL and GH secretion in the mother and fetus, suggests that the factors regulating PL and GH secretion in the mother and fetus are distinct.