Diagnosis and treatment of gestational diabetes according to amniotic fluid insulin levels

In spite of dietary treatment, the infants of pregnant patients with abnormal glucose tolerance have hyperinsulinism and diabetogenic fetopathy in 10 to 36% of cases. Those patients, who require insulin to prevent from fetopathy cannot be reliably selected by maternal parameters such as blood glucose and glycosylated hemoglobin values. We recommend the measurement of amniotic fluid insulin between the 28 and 32 weeks of pregnancy to differentiate whether the fetus is compromised or not. Subjects with values above the 97th centile require insulin therapy. Inadequate insulin dosage or delayed fetal hyperinsulinism can be discovered by checking the amniotic fluid insulin level at 33 to 36 weeks. In a total of 88 gestational diabetic patients 19 had raised amniotic fluid insulin levels indicating the onset of diabetic fetopathy at an early stage. Diabetic patients with raised amniotic fluid insulin levels needed large doses of insulin, namely 64.6 +/- 29.5 (Mean +/- SD) U/24 h. This treatment reduced mean blood glucose levels from 98 +/- 9 (Mean +/- SD) mg/dl to 82 +/- 10 mg/dl and was sufficient to prevent from diabetic fetopathy.     

Insulin levels in amniotic fluid. Management of pregnancy in diabetes

A correlation between high insulin levels in amniotic fluid and the appearance of diabetogenic fetal morbidity was found in radioimmunoassays of 487 samples of the fluid. The mean insulin level in metabolically normal pregnancies rose from 9 muU/ml (Week 27) to 15 muU/ml (Week 40). The insulin level in amniotic fluid of diabetic patients was elevated up to 27 times the mean. Insulin levels in the umbilical cord and urine of newborns of diabetic mothers were also elevated, to 29 and 21 times the mean, respectively. Elevation of insulin levels in amniotic fluid portends diabetogenic fetal morbidity. High and rising insulin levels at an early stage (26-28 weeks) may indicate a high risk of preterm onset of labor. Regular adjustment of metabolic compensation on the basis of amniotic fluid insulin made it possible to reduce the level in 12 of 17 pregnant diabetic women by increasing insulin dosage. The 12 women were thereby enabled to carry their pregnancies to term and to await the onset of spontaneous labor without diabetogenic fetal morbidity. Beta-stimulating agents affect glucose management and may cause elevated insulin levels in amniotic fluid.     

Fetal beta cell function in diabetic pregnancy. Amniotic fluid concentrations of proinsulin, insulin, and C-peptide during the last trimester of pregnancy

Proinsulin, insulin C-peptide, insulin-binding antibody, and glucose concentrations were measured in amniotic fluid samples from 43 insulin-treated diabetic patients and 17 nondiabetic control patients between the thirty-six and thirty-ninth weeks of gestation. Insulin-binding antibodies in amniotic fluid were present in only three diabetic patients, although antibodies in maternal serum were found in 22 of the diabetic subjects. In the diabetic group, maternal serum insulin-binding antibodies were statistically unrelated to levels of C-peptide in amniotic fluid. The mean amniotic fluid concentrations of proinsulin (0.07 nmole/L), insulin (0.08 nmole/L), C-peptide (1.17 nmoles/L), and glucose (2.09 mmoles/L) were markedly elevated (p less than 0.001) in diabetic patients, as compared to nondiabetic control patients, thus suggesting exaggerated fetal beta cell function. C-peptide was correlated to both insulin (r = 0.69) and proinsulin (r = 0.35) in the diabetic group only. Infant birth weight and amniotic fluid C-peptide was significantly correlated in both the control group (r = 0.54) and the diabetic group (r = 0.38). Diabetic pregnancies associated with neonatal morbidity (n = 25) had significantly higher mean amniotic fluid concentrations of both insulin and C-peptide than did pregnancies without neonatal morbidity (n = 18). The amniotic fluid values of C-peptide and insulin in these latter two subgroups were overlapping and, therefore, could not serve to predict neonatal outcome in the individual case.     

Fetal lung maturity in diabetic pregnancies: relation among amniotic fluid insulin, prolactin, and lecithin

Insulin, prolactin, and lecithin phosphorus levels were measured in 97, 62, and 44 amniotic fluid samples from third trimester normal, gestational diabetic, and insulin-dependent diabetic patients, respectively. There was no difference in lecithin phosphorus concentration (index of fetal lung maturity) among the three groups. The amniotic fluid insulin level was significantly higher in insulin-dependent diabetic patients, whereas there was no difference in amniotic fluid prolactin levels among the groups. Correlations of amniotic fluid prolactin levels with both lecithin phosphorus and insulin levels were not statistically significant in any of the groups. This is probably because amniotic fluid prolactin is decidual, rather than fetal, in origin. Even though amniotic fluid insulin levels, which reflect fetal levels, were significantly higher in insulin-dependent diabetic patients, there was no difference in the amniotic fluid lecithin phosphorus concentration in diabetic pregnancies compared with that in normal pregnancies. Moreover, there was a positive, and not a negative, correlation between amniotic fluid insulin and amniotic fluid lecithin phosphorus levels in diabetic pregnancies. These results do not support the theory that fetal hyperinsulinemia results in delayed pulmonic maturation in diabetic pregnancies.     

Amniotic fluid insulin,C peptide concentrations,and fetal morbidity in infants of diabetic mothers

Glucose, insulin, C peptide, and insulin antibody concentrations were measured in amniotic fluid collected under basal conditions and 2 hours after an arginine challenge from 61 insulin-treated diabetic women (12 basal and 49 after arginine challenge) and 31 nondiabetic pregnant women in late gestation (23 basal and eight after arginine challenge). The insulin, C peptide, and glucose concentrations were significantly higher in diabetic pregnant women than in nondiabetic pregnant women in each case. In the amniotic fluid obtained after arginine challenge in diabetic pregnant women, C peptide concentration was correlated with both insulin concentration (r = 0.61) and birth weight (r = 0.53). The insulin and C peptide concentrations were significantly higher (p < 0.025) in samples from diabetic pregnancies associated with fetal morbidity than from diabetic pregnancies without fetal morbidity. Basal amniotic fluid insulin and C peptide concentrations were slightly greater in overweight infants of diabetic mothers compared to those of normal weight, whereas the differences for insulin and C peptide concentrations in the amniotic fluid obtained after arginine challenge were highly significant (p < 0.0125 and p < 0.0005, respectively). Finally insulin and C peptide concentrations in the amniotic fluid obtained after arginine challenge in diabetic pregnant women showed a correlation with maternal metabolic control but not with the degree (White classification) of maternal diabetes. No or negligible interference of insulin antibody in the radioimmunoassay of insulin in amniotic fluid was observed.     

Serum fructosamine and amniotic fluid insulin levels in patients with gestational diabetes and healthy control subjects

Gestational diabetic pregnancies with fetal hyperinsulinism should be identified because these cases require insulin therapy. To determine the relationship between the serum fructosamine and amniotic fluid insulin concentrations, these substances were measured in 87 pregnant women with impaired glucose tolerance. Fructosamine was also measured in 678 healthy pregnant control subjects, in 113 of whom amniotic fluid insulin levels were available. Fetal hyperinsulinism was rare at serum fructosamine levels of less than 2.6 mmol/L. These results suggest that when both the oral glucose tolerance test and fructosamine level are used, only 30% of women with gestational diabetes need to undergo amniocentesis to assess fetal insulin homeostasis.     

Fetal pancreatic function in infants of diabetic and rhesus-isoimmunized women

OBJECTIVE: To measure insulin and glucagon concentrations in amniotic fluid (AF) collected near term in basal conditions and after an arginine test in diabetic, rhesus-isoimmunized, and control pregnant women. METHODS: At baseline, AF was collected from 44 diabetic, 32 rhesus-isoimmunized, and 27 control pregnant women in late pregnancy. Fifty-two diabetic, six rhesus-isoimmunized, and nine control pregnant women had amniocentesis 2 hours after arginine infusion (30 g intravenous/30 minutes) at 33-36 weeks. RESULTS: Baseline AF glucose concentrations were significantly greater in diabetic women than the other conditions, and they related to the gestational age in the women with hemolytic disease of the newborn. Insulin and glucagon AF content of isoimmunized pregnancies overlapped controls, whereas insulin and insulin/glucagon molar ratios were significantly higher, and glucagon values lower, in diabetic pregnancies compared with isoimmunized and control pregnancies. In isoimmunized pregnancies, the AF concentrations of glucose, insulin, and glucagon were correlated with gestational age (less than 34, 34 weeks or more). The samples collected after arginine infusion, compared with those collected at baseline, showed significantly greater insulin and insulin/glucagon molar ratio values in diabetic (28 +/- 5 versus 11 +/- 1 microU/mL, P = .001; 29.4 +/- 1.7 versus 12.0 +/- 2.8, P = .001) and in Rh pregnant women (18 +/- 6 versus 7.7 +/- 0.7 microU/mL, P = .001; 30 +/- 9 versus 3.4 +/- 0.4 I/G, P = .001), whereas no significant difference was observed in the controls. CONCLUSION: Basal islet hormone concentrations in AF are modified by maternal diabetes and further influenced by arginine administration. Arginine produces an AF response that is similar in pregnancies complicated by diabetes mellitus and rhesus-isoimmunization, despite different (hyperglycemia and euglycemia) maternal blood glucose levels.     

Effect of fetal hyperinsulinism on oral glucose tolerance test results in patients with gestational diabetes mellitus

OBJECTIVE: This study was undertaken to evaluate the impact of the fetoplacental glucose steal phenomenon on the results of oral glucose tolerance testing in pregnancies complicated by gestational diabetes mellitus with fetal hyperinsulinism. STUDY DESIGN: This was an analysis of the cases of 34 patients with two consecutive abnormal oral glucose tolerance test results and amniotic fluid insulin measurement before institution of insulin therapy. Patients were divided into groups on the basis of normal versus elevated amniotic fluid insulin concentrations. RESULTS: Oral glucose tolerance tests were done at a mean (+/-SD) of 24.9 +/- 5.7 and 30.7 +/- 3.2 weeks' gestation, and amniotic fluid insulin measurements were done at 31.1 +/- 3.2 weeks' gestation. In 13 women with gestational diabetes mellitus with normal amniotic fluid insulin concentration, maternal postload blood glucose levels at 1 hour increased by 12 mg/dL (168 vs 180 mg/dL; 9.3 vs 10.0 mmol/L; P = .0006) during the course of 6 weeks. In contrast, in 21 women with gestational diabetes mellitus with elevated amniotic fluid insulin levels (>7 microU/mL; >42 pmol/L), 1-hour postload blood glucose levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P = .002) during the same period. The higher the amniotic fluid insulin level, the larger the decrease (R = 0.504; P =.02). Although low amniotic fluid insulin levels were correlated significantly with 1-hour glucose levels of the first and second oral glucose tolerance tests, high insulin levels were no longer correlated with the second oral glucose tolerance test. CONCLUSION: Exaggerated fetal glucose siphoning may provide misleading oral glucose tolerance test results in pregnancies complicated by fetal hyperinsulinism by blunting maternal postload glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy complicated by gestational diabetes mellitus with a fetus that already has hyperinsulinemia may erroneously be considered normal.     

Amniotic fluid beta-endorphin and beta-lipotropin concentrations during the second and third trimesters

Amniotic fluid beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were measured by radioimmunoassay after silicic acid extraction and gel chromatographic separation of the two peptides in uncomplicated second-trimester and term pregnancies, in diabetic patients at term, and in pregnancies complicated by Rh-isoimmunization, premature labor, and intrauterine growth retardation. Furthermore, the lecithin/sphingomyelin (L/S) ratios as well as the dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels were determined in most of the amniotic fluid specimens. Both the mean (+/- SE) beta-EP (65.3 +/- 9.1 fmol/ml) and beta-LPH (150 +/- 15.8 fmol/ml) concentrations were significantly higher in the 20 patients with normal pregnancies of 16 to 21 weeks' duration than those found in 21 patients with uncomplicated term pregnancies of 38 weeks' gestation, averaging 42.6 +/- 6.0 and 80.1 +/- 10.7 fmol/ml, respectively. The mean amniotic fluid beta-EP and beta-LPH concentrations measured in the latter subjects were similar to those observed in 23 diabetic patients with otherwise uncomplicated term pregnancies. The mean amniotic fluid beta-EP and beta-LPH levels found in the limited number of patients with Rh-isoimmunization (N = 9), premature labor (n = 8), and intrauterine growth retardation (n = 5) with pregnancies of 24 to 36, 24 to 36, and 34 to 38 weeks' gestation, respectively, were not significantly different from the mean amniotic fluid beta-EP and beta-LPH concentrations of uncomplicated term pregnancies. In all patients but those with Rh-isoimmunization, beta-EP concentrations exhibited a positive correlation with beta-LPH levels. However, the molar beta-LPH:beta-EP ratio was significantly lower at term than during the early second trimester. Neither beta-EP nor beta-LPH correlated with the amniotic fluid L/S ratio and only beta-LPH exhibited a significant inverse correlation with amniotic fluid DHEA-S. The latter was significantly higher in uncomplicated term than second-trimester pregnancies. These results confirm that immunoassayable beta-EP is present in amniotic fluid and declines toward term. These data demonstrate that immunoassayable beta-LPH is present in amniotic fluid and show a more pronounced decrease toward the end of pregnancy than beta-EP. Neither peptide, at least on account of the amniotic fluid levels, appears to be associated with fetal maturation. The physiologic significance of amniotic fluid beta-EP and beta-LPH and their possible role as markers of fetal response to stress remain to be elucidated.     

Amniotic fluid protease activity, protease inhibitory activity, and fetal lung maturity

Amniotic fluid acid protease and acid protease inhibitory activities were examined in normal pregnancies as a function of gestational age. The acid proteolytic activity of the amniotic fluid is almost constant during gestational weeks 16-29 (26 +/- 13 micrograms globin/ml/2 hrs, mean +/- SD, n = 64). The activity sharply increases after 29 weeks in a time-dependent fashion and reaches a value of 302 +/- 89 (mean +/- SD, n = 13) at 39-40 weeks gestation. Under standard conditions, the ability of amniotic fluid to inhibit bovine pepsin declined during gestation in a linear fashion from 44 +/- 13% (mean +/- SD, n = 36) at 16-18 weeks to 9 +/- 10% (mean +/- SD, n = 41) at 36-40 weeks. A correlation coefficient of r = 0.72 was found between pepsin inhibitory activity and gestational age. No consistent change was noted in the extent of inhibition of the endogenous acid protease throughout pregnancy. In 61 amniotic fluid samples, a correlation coefficient of r = 0.70 was found between acid protease activity and the lecithin/sphingomyelin (L/S) ratio. During the course of this study, five cases of respiratory distress syndrome (RDS) were diagnosed clinically. All five infants had a low protease activity (55 +/- 22 micrograms globin/ml/2 hr, mean +/- SD) as well as a low L/S ratio (0.68 +/- 0.20, mean +/- SD). In contrast, no case of RDS of the newborn was observed among 29 pregnancies with high protease activity and a high L/S ratio. The present observations may suggest a predictive value of amniotic fluid acid protease activity in assessment of fetal lung maturity.     

Alterations of maternal metabolism in normal and diabetic pregnancies: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes

In normal and diabetic pregnancies, the placenta functions as a complex endocrine gland that modulates all classes of maternal nutrients to the fetus. The metabolic alterations of normal pregnancy are diabetogenic and associated with modest resistance to endogenous insulin. Pregnant women with carbohydrate intolerance represent three metabolically heterogeneous groups: type I (insulin-dependent), type II (non-insulin-dependent), and gestational diabetes. Patients with type I diabetes are at risk for ketosis and require replacement therapy because of a deficient production of insulin. They have decreased 24-hour, around-the-clock levels of C-peptide and glucagon, and lower nocturnal cortisol values and higher 24-hour prolactin levels than those of women with type II diabetes. Type II pregnant diabetic patients are not prone to ketosis and are more resistant to endogenous and exogenous insulin. They have higher fasting and meal-stimulated levels of C-peptide, accentuated fasting hypertriglyceridemia, and significantly lower high-density lipoprotein cholesterol levels than those of normal or type I women. In gestational diabetes, the metabolic stress of pregnancy evokes reversible hyperglycemia which may be associated with either a surfeit or a deficiency of insulin. These metabolic differences among diabetic pregnant women could have implications for placental structure and function that might influence fetal growth.     

Elevated amniotic fluid leptin levels in early second trimester are associated with earlier delivery and lower birthweight in twin pregnancy

OBJECTIVE: To explore the possibility of using early second trimester amniotic fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. STUDY DESIGN: Amniotic fluid leptin levels from 18 twin-pregnant women in early second trimester were analyzed for their correlation with gestational age at delivery and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from small for gestational age (SGA) twin pregnancies were compared with those in 20 amniotic fluid samples collected from non-SGA twin pregnancies. RESULTS: A significant correlation was observed between amniotic fluid leptin levels and gestational age at delivery (r = 0.71, p < 0.001) as well as fetal birthweight (r = 0.72, p < 0.001). There was also a significant correlation between gestational age at delivery and fetal birthweight (r = 0.92, p < 0.001). The average gestational age at delivery was 30.4 +/- 1.4 weeks in the SGA group, with a mean birthweight of 1552 +/- 200 g at delivery. For the non-SGA group, the values were 37.3 +/- 0.5 weeks and 2759 +/- 115 g ( p < 0.001), respectively. Amniotic fluid leptin levels were found to be significantly higher ( p < 0.001) for women in the SGA group (11.4 +/- 1.5 ng/mL) than for those in the non-SGA group (5.4 +/- 0.5 ng/mL). CONCLUSION: Higher amniotic fluid leptin levels in early second trimester were associated with both lower gestational age at delivery and lower birthweight. Our results suggest that amniotic fluid leptin levels in early second trimester may be a good marker for the prediction of perinatal complications in twin pregnancy.     

Surfactant associated protein (SAP-35) in amniotic fluid from diabetic and nondiabetic pregnancies

We have recently shown that, with the current management of insulin-dependent diabetes during pregnancy, infants of diabetic mothers are at no greater risk of respiratory distress syndrome (RDS) than an appropriately matched control population. A previous study suggested a selective inhibition of surfactant associated protein of 35,000 daltons (SAP-35) in the amniotic fluid of diabetic pregnancies. In order to determine whether a selective inhibition of SAP-35 occurs in well controlled, insulin-dependent diabetic pregnancies, we compared SAP-35 concentration and lecithin/sphingomyelin (L/S) ratios in amniotic fluid from 30 well controlled, insulin-dependent women with 30 nondiabetic pregnant women pair-matched for gestational age, race, and indication for amniocentesis. Gestational ages ranged from 30-43 weeks, with a mean of 36.5 +/- 2.5 weeks, in both groups. Surfactant associated protein-35 was measured by an enzyme-linked capture immunoassay specific for SAP-35 and its oligomers. Mean +/- SEM SAP-35 was 3.7 +/- 0.4 micrograms/mL (N = 30) in the diabetic group, not significantly different from 5.0 +/- 1.1 micrograms/mL (N = 30) in the control group (P greater than .05). Mean L/S ratios were also not different: 2.4 +/- 0.1 (diabetic) compared with 2.3 +/- 0.1 (control); P greater than .05. The rate of RDS was similar in both groups. We conclude that in well controlled diabetic pregnancies, fetal lung maturation, as assessed by the L/S ratio, SAP-35 concentration, and outcome, is not adversely affected.     

Differences in amniotic fluid patterns and fetal biometric parameters in third trimester pregnancies with and without diabetes.

OBJECTIVE: The amniotic fluid index (AFI) has been increasingly used in the assessment of fetal well-being. We conducted the study to evaluate and compare the amniotic fluid index in third trimester normal and diabetic human pregnancy and to assess the correlation between the AFI and the fetal biometric parameters. METHODS: Real-time ultrasound was performed to evaluate the AFI (four-quadrant technique), and to measure the biparietal diameter, head circumference, abdominal circumference, and femur length in 225 normal and 120 diabetic pregnant women from 27 to 42 weeks of gestation. Each patient was studied only once. RESULTS: AFI in normal pregnancies was less than that in diabetic pregnancies throughout the gestational ages studied (27-42 weeks). In normal pregnancy, the mean AFI was 14.0 cm at 27 weeks and decreased to 11.4 cm at 42 weeks (r = 0.25, p = 0.0005), whereas in diabetic pregnancies, the values remained stable throughout the gestational ages studied. There exist significant differences in AFI, estimated fetal weight, estimated fetal weight %, abdominal circumference, abdominal circumference %, and head circumference to abdominal circumference ratio between the two groups. In both normal and diabetic pregnancies, there is a positive correlation between the AFI and the percentile of abdominal circumference (p < 0.0001), and between the AFI and the percentile of estimated fetal weight (p < 0.0001). CONCLUSION: This study provides gestational age-specific values of the AFI in normal and diabetic pregnancies. Diabetic pregnancy has greater AFI values than normal pregnancy between 27 and 42 weeks. The AFI correlates to the percentile of the estimated fetal weight and the abdominal circumference in both groups, suggesting that there may be a relationship between increased AFI and large for gestational age fetus independent of diabetes.     

Fetal malformation and serum alpha-fetoprotein concentration of diabetic mothers

Diabetic pregnant patients belong to a high-risk group from a genetic counselling point of view. Therefore serum AFP estimation and ultrasound examination was carried out in 36 diabetic pregnancies, between the 16-20 gestational weeks. Healthy infants were delivered in 28 cases, fetal malformations or diseases were diagnosed in 3 cases (2 exencephaly and 1 polycystic kidney disease), 5 pregnancies ended up with stillbirth and/or severe fetopathy. According to our findings, the feto-maternal AFP balance is altered in poorly controlled diabetic pregnant patients. Therefore the maternal serum AFP concentration does not always reflect the AFP content of amniotic fluid. It is supposed that the low serum AFP concentration in diabetic patients is due to the disturbed AFP balance, which cannot be observed in well controlled pregnant diabetics. In the pregnancy of diabetic mothers both serum AFP and ultrasound examination should be carried out. With further improvement in the preconceptional treatment of diabetic patients not only the number of malformations caused by hyperglycaemia should diminish, but the problems of false negative and false positive serum AFP values caused by the disturbance in carbohydrate metabolism should also become less frequent.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

Amino acid concentrations in maternal plasma and amniotic fluid in relation to fetal insulin secretion during the last trimester of pregnancy in gestational and type I diabetic women and women with small-for-gestational-age infants

Free amino acid concentrations were determined in maternal plasma and amniotic fluid (AF) under standardized and unstressed conditions in four groups of women comprising 6 gestational and 13 type I diabetics, 10 women with small-for-gestational-age (SGA) infants, and 18 healthy control women between 36 and 39 weeks of gestation. Plasma values for branched chain amino acids (the sum of leucine, isoleucine and valine) did not differ significantly between the four groups. The corresponding values in AF were significantly higher (P less than 0.05) in the type I diabetic group and significantly lower (P less than 0.05) in the gestational diabetic group as compared to the control group. The mean AF C-peptide concentration was elevated but not significantly so in gestational (0.69 nmol/l) or type I diabetic (0.54 nmol/l) pregnancies and significantly lower (P less than 0.05) in women with SGA infants (0.28 nmol/l) as compared to the control group (0.38 nmol/l). There was a significant correlation between C-peptide in AF and branched chain amino acids in maternal plasma (r = 0.63; P less than 0.05) as well as to maternal blood glucose (r = 0.79; P less than 0.01) in the type I diabetic group, which merely suggests a greater beta cell reactivity to insulin secretagogues in offspring of diabetic mothers. The correlation between AF C-peptide and branched chain amino acids in maternal plasma was significantly inverse in women with SGA infants (r = -0.75; P less than 0.05). Both individual, branched chain, or total amino acid concentration in AF were unrelated to AF C-peptide.     

Gestational diabetes and screening during pregnancy

The oral glucose tolerance test is an unreliable test in screening for diabetogenic fetal disease. In diabetogenic fetopathy due to gestational diabetes (White class A diabetes), the insulin content in the umbilical cord blood as well as in the fetal urine is considerably raised. As increased amounts of insulin pass into the amniotic fluid via the fetal urine, the fetal disease can be diagnosed from the amniotic fluid insulin content. In 75 pregnant women with potential diabetes, the blood sugar value was below 160 mg/dL at maximum under glucose loading in 28 patients; it was over 200 mg/dL in 25 patients. However, diabetogenic fetopathy was present in only 14 patients. The endangered and the healthy fetus could be distinguished in each case by amniotic fluid insulin content. The mean amniotic fluid insulin values in diabetogenic fetopathy were about seven times the normal.     

Decreased amniotic fluid magnesium concentration in diabetic pregnancy

Amniotic fluid samples from 21 diabetic pregnant women were pair-matched for gestational age with 21 samples obtained from nondiabetic women, and analyzed for magnesium concentration. Mean +/- standard deviation amniotic fluid magnesium concentration (mg/dL) was 0.86 +/- 0.21 in the diabetic group and 1.06 +/- 0.22 in the control group (P less than .001). It is concluded that in the diabetic pregnancy, a state of fetal magnesium deficiency exists. This deficient state may contribute to neonatal hypocalcemia in infants of diabetic mothers.     

Amniotic fluid phosphatidylglycerol in diabetic pregnancies

Despite L/S ratios indicating fetal lung maturity, respiratory distress continues to occur more frequently in infants of diabetic mothers. Amniotic fluid pulmonary phospholipids were studied in an attempt to understand the occurrence of false-positive L/S ratios in preterm diabetic pregnancies. Qualitative chromatographic assays of surfactant phosphatides revealed reduced or absent phosphatidylglycerol in diabetic amniotic fluid specimens between 34 and 37 weeks' gestation. Mean phosphatidylglycerol in 15 nondiabetic and 29 diabetic specimens was 16 and 4 per cent of total extracted pulmonary phospholipids (P < 0.001). Non-insulin-dependent diabetic pregnancies had lowest mean per cent phosphatidylglycerol. Respiratory distress occurred in six infants of diabetic mothers delivered preterm with L/S ratios of 2:1 or greater; phosphatidylglycerol was absent in five. The inclusion of phosphatidylglycerol in amniotic fluid phospholipid assessment may be an adjunctive index for fetal lung maturation in diabetic pregnancies.