Hepatic and peripheral responsiveness to a glucose infusion in pregnancy

To enhance glucose transfer to the fetus, the pregnant woman may evidence hyperglycemia after feeding. In order to evaluate whether hepatic responsiveness, in contrast to peripheral uptake, contributes to this response, the glucose production rate was measured in 15 pregnant nondiabetic patients, in 12 pregnant insulin-dependent diabetic patients, and in 12 nonpregnant nondiabetic patients (controls). Seventeen of the women were infused with 3.2 mg X kg-1 min-1 of glucose. All glucose-infused groups had an elevated plasma glucose concentration compared to their saline solution-infused counterparts. The glucose production rate was suppressed in the nondiabetic glucose-infused groups. The glucose production rate of the pregnant nondiabetic patients was similar to that of the pregnant insulin-dependent diabetic patients, but the glucose production rate of the latter group was more variable than that of nonpregnant nondiabetic controls (p less than 0.05). We conclude that in third trimester, pregnant nondiabetic and insulin-dependent diabetic subjects have parallel hepatic and peripheral responsiveness to glucose and insulin compared to their nonpregnant counterparts. Although the pregnant patient may exhibit relative insulin insensitivity, hepatic or peripheral responsiveness to insulin would not explain the persistence of the relative hyperglycemia noted clinically.     

Does intensive glycemic control in diabetic pregnancies result in normalization of other metabolic fuels?

Intensive treatment of insulin-dependent diabetes mellitus during pregnancy often normalizes plasma glucose levels. However, it is unclear whether this adversely affects other metabolic fuels that are essential to normal fetal growth and development. Metabolic studies were conducted after the subjects ingested a standardized mixed meal during each trimester in 7 normal and 15 insulin-dependent diabetic pregnant women. The latter were treated with continuous subcutaneous insulin infusion or multiple injections, which were adjusted to achieve strict glucose control throughout pregnancy. Insulin, alanine, branched-chain amino acids, triglycerides, free fatty acids, and ketones were measured every 15 to 30 minutes before a standardized breakfast and for 150 minutes after the breakfast. Patients with insulin-dependent diabetes mellitus were studied while they received their unusual insulin dosages. Fasting glucose levels (87 +/- 7 mg/dl) and glucose levels 150 minutes after the meal (112 +/- 11 mg/dl) were near normal. However, normoglycemia was achieved at the expense of increased plasma insulin levels (area under insulin response curves, p less than 0.01, vs nondiabetic curves). Nevertheless, fasting and post-prandial plasma branched-chain amino acids, alanine, and free fatty acids were similar in both groups. Fasting cholesterol, triglyceride, and ketone levels were also normalized. We conclude that normalization of circulating amino acids and lipids in conjunction with correction of hyperglycemia may contribute to favorable outcomes in infants of intensively treated diabetic mothers.     

Endocrine pancreatic sensitivity to glucose in women with gestational diabetes

To study whether gestational diabetes is the result of abnormal endocrine pancreatic adaptation to pregnancy, alpha- and beta-cell sensitivity to glucose was determined during pregnancy and post partum in seven women of normal weight who had gestational diabetes. Glucose was infused intravenously in quantities producing similar increases in plasma glucose in pregnancy and post partum, and the plasma glucose curves obtained closely resembled those found during an oral glucose tolerance test. The insulin response to the infusion was 3.5 times greater in pregnancy (P less than .02), whereas glucagon was suppressed similarly in pregnancy and post partum. These findings resemble previous ones in normal women. It is concluded that pancreatic alpha and beta cells adapt similarly to pregnancy in women with gestational diabetes and in normal women.     

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.

OBJECTIVES: The purpose of this study was to determine the incidence of diabetes in women with previous dietary-treated gestational diabetes mellitus and to identify predictive factors for development of diabetes. STUDY DESIGN: Two to 11 years post partum, glucose tolerance was investigated in 241 women with previous dietary-treated gestational diabetes mellitus and 57 women without previous gestational diabetes mellitus (control group). RESULTS: Diabetes developed in 42 (17.4%) women with previous gestational diabetes mellitus (3.7% insulin-dependent diabetes mellitus and 13.7% non-insulin-dependent diabetes mellitus). Diabetes did not develop in any of the controls. Predictive factors for diabetes development were fasting glucose level at diagnosis (high glucose, high risk), preterm delivery, and an oral glucose tolerance test result that showed diabetes 2 months post partum. In a subgroup of previous patients with gestational diabetes mellitus in whom plasma insulin was measured during an oral glucose tolerance test in late pregnancy a low insulin response at diagnosis was found to be an independent predictive factor for diabetes development. CONCLUSIONS: Women with previous dietary-treated gestational diabetes mellitus have a considerably increased risk of later having diabetes. Follow-up investigations are therefore important, especially in those women with previous gestational diabetes mellitus in whom the identified predictive factors are present.     

Accelerated starvation in late pregnancy: a comparison between obese women with and without gestational diabetes mellitus

We compared the glucose, insulin, free fatty acid, and 3-hydroxybutyrate responses to a briefly extended overnight fast during the third trimester of pregnancy between two groups: obese women with normal glucose tolerance (n = 10) and age- and weight-matched women with gestational diabetes mellitus (n = 10). After a 12-hour overnight fast, plasma glucose (95 +/- 4 vs. 78 +/- 2 mg/dl; p less than 0.01), insulin (32 +/- 5 vs. 17 +/- 2 microU/ml; p less than 0.02), and free fatty acid (860 +/- 63 vs. 639 +/- 79 mmol/L; p less than 0.05) levels were higher in the patients with gestational diabetes mellitus. 3-Hydroxybutyrate levels were similar in the two groups at that time (0.23 +/- 0.04 vs. 0.18 +/- 0.03 mmol/L; p greater than 0.3). When the fast was extended to 18 hours by having the patients skip breakfast, glucose levels fell more rapidly in the group with gestational diabetes mellitus but remained elevated compared with the nondiabetic women. Insulin levels declined at a similar rate in the two groups. Free fatty acid levels did not increase significantly in the group with gestational diabetes mellitus during the extended fast. In contrast, free fatty acid levels increased by 44% in the normal pregnant women, reaching the level observed in the group with gestational diabetes mellitus after 18 hours. 3-Hydroxybutyrate levels remained virtually identical in the two groups throughout the brief fast. Thus, compared with that of normal pregnant women, the response of obese women with gestational diabetes mellitus to brief caloric deprivation during late pregnancy was characterized by a greater fall in plasma glucose values without a greater propensity to ketosis. Our findings may have important implications for the dietary management of obese patients with gestational diabetes mellitus.     

Glycohemoglobin in diabetic pregnancy: a sequential study

Glycohemoglobin (Hb Alc) was assayed sequentially during pregnancy and post partum in 53 women. In a group of nondiabetic women (N = 13) Hb Alc fell significantly (p less than 0.001) from the first to the third trimester and then rose to first-trimester levels by 12 weeks' post partum. Glycohemoglobin levels of insulin-dependent diabetic patients (N = 28) followed a similar pattern but at significantly elevated levels compared to nondiabetic patients (p less than 0.001). In contrast, patients with chemical diabetes (N = 12) did not manifest any change of Hb Alc with time, although they did have glycohemoglobin levels above those of the normal subjects during the third trimester (p less than 0.001) and before 12 weeks' post partum (p less than 0.02). It is speculated that these fluctuations in Hb Alc are most likely due to changes in long-term blood glucose control. Additionally, because Hb Alc increased in vitro oxygen affinity, some of these women were followed for parameters of oxygen transport as well. No significant changes of parameters of oxygen transport were found, with the exceptions of P50 in vivo and P50pH7.40 during the third trimester and of P50 in vivo before 12 weeks' post partum     

Maternal plasma leptin levels and their relationship to insulin and glucose in gestational-onset diabetes

To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation. We also correlated maternal plasma leptin levels in diabetic women with fasting plasma insulin levels and plasma glucose levels obtained 1 h after oral administration of 50 g of glucose. Maternal serum leptin levels in women with gestational diabetes (mean +/- SD 16.52 +/- 5.07 ng/ml, range 10.84-27.4 ng/ml) were significantly higher (p < 0.001) than those found in uncomplicated pregnancies (10.61 +/- 1.47 ng/ml, range 7.28-13.4 ng/ml). A positive correlation was found between maternal serum leptin levels and glycosylated haemoglobin values in diabetic pregnant women (r = 0.94, p < 0.001). A positive correlation was also found between maternal leptin concentrations and fasting serum insulin levels, as well as between leptin concentrations and plasma glucose levels obtained 1 h after the administration of 50 g of glucose in women with gestational diabetes (r = 0.84, p < 0.001, and r = 0.92, p < 0.001, respectively). We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.     

Insulin-induced hypoglycaemia in diabetic women during late pregnancy and one year post partum

Insulin (0.1 IW/kg) later followed by glucose was injected intravenously in nine diabetic women in the supine position both during pregnancy and one year post partum. C-peptide was present in five subjects, indicating some residual beta-cell function. Their mean basal C-peptide level, before insulin, was twice as high in the pregnant as inthe non-pregnant state. C-peptide decreased progressively after insulin. The mean basal plasma glucose level was lower during pregnancy (4.8 mmol/l) than after it (9.6 mmol/l), but decreased to the same level (2.2 mmol/l) after insulin. The rate of fall in glucose was thus lower during pregnancy (kt = 2.54) than after (kt = 4.08), but was unrelated to the basal glucose levels. Basal levels of free fatty acids (FFA), 3-hydroxybutyrate (3-HB), cyclic AMP, and lactate were similar, while glycerol was lower during pregnancy. Insulin-induced changes in FFA, glycerol, 3-HB, cyclic AMP, and lactate were similar during and after pregnancy. Plasma amino acid concentrations were generally lower in pregnancy, significantly so only for arginine and glycine. Amino acid levels were unaffected by insulin in pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy state. We conclude that there are differences in metabolic responses to insulin in diabetic women during and after pregnancy, indicating a decreased sensitivity to insulin during pregnancy in some tissues.     

Randomized trial of human versus animal species insulin in diabetic pregnant women: improved glycemic control, not fewer antibodies to insulin, influences birth weight.

OBJECTIVE: Macrosomia occurs in infants of diabetic mothers in spite of "nearly normal maternal blood glucose levels" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin. STUDY DESIGN: Forty-three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge. RESULTS: Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01). CONCLUSION: Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight.     

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.     

Serum levels of 1,5-anhydro-D-glucitol during the normal and diabetic pregnancy and puerperium

In 25 normally non-pregnant women, 543 normally pregnant women and 75 pregnant women with diabetes mellitus or gestational diabetes mellitus, the relationship between the serum concentration of 1,5-anhydro-D-glucitol (1-deoxy-glucose) and carbohydrate metabolism was studied. The concentration of 1,5-anhydro-D-glucitol was estimated by means of gas-liquid chromatography. In normally non-pregnant women the concentration was found to be 18.6 +/- 5.2 mg/l (mean +/- SD). During the normal pregnancy, from 9 weeks of gestation, a steadily decreasing concentration was observed as the pregnancy progressed and the lowest value (10.2 +/- 4.6 mg/l) was found in the third trimester. After 5 days of puerperium the concentrations were found to be 10.8 +/- 3.7 mg/l. On the 30th day postpartum, the level was within the range for non-pregnant subjects. The values in pregnant women with diabetes mellitus and gestational diabetes mellitus were mostly below 10 mg/l throughout the entire pregnant period. The 1,5-anhydro-D-glucitol concentration was not affected by meals or oral glucose loading. A concentration below 10 mg/l was found in 36% of the normally pregnant women, where oral glucose tolerance tests and measurement of glycohemoglobin were shown to be within the normal range. The present study suggests that a change of 1,5-anhydro-D-glucitol level during pregnancy may reflect a mild alteration of carbohydrate metabolism that goes undetected by all the other diabetic indicators.     

Sex hormone-binding globulin in gestational diabetes

BACKGROUND: Insulin is an important regulator of serum sex hormone-binding globulin (SHBG) concentration which works by inhibiting its production in hepatocytes. Low SHBG level is associated with increased insulin resistance and hyperinsulinemia. Our purpose was to compare maternal serum SHBG level between normal and gestational diabetic pregnant women and to study the relationships between SHBG, SHBG/insulin and SHBG/glucose ratio and several endocrine, metabolic and clinical parameters. METHODS: Serum SHBG concentrations were measured in 34 women with gestational diabetes and in 32 matched controls. Glucose, insulin, C-peptide, fructosamine, beta-HCG, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A, apolipoprotein B, total and free T4, total and free estriol, T3 and IGF-1 were measured. Insulin sensitivity was estimated using the short insulin tolerance test. RESULTS: SHBG, SHBG/insulinemia ratio and SHBG/glucose ratio were significantly lower in the diabetic group (309.54 +/- 112.22 vs 460.54 +/- 144.54, p = 0.00001), (33.55 +/- 16.62 vs 72.56 +/- 66.50, p = 0.0006 using log-transformed values), (5.88 +/- 1.87 vs 3.39 +/- 1.23, p < 0.00001). SHBG was negatively correlated with insulinemia (r = -0.40, p = 0.001), C-peptide (r = -0.41, p = 0.001), glycemia (r = -0.27, p = 0.02), diastolic blood pressure (r = -0.41, p = 0.001) and beta-HCG (r = -0.41, p = 0.001) and positively correlated with LDL-c (r = 0.25, p = 0.04) and apolipoprotein B (r = 0.33, p = 0.007). CONCLUSIONS: SHBG concentrations are lower in gestational diabetic pregnant women and are related to insulin levels but not to peripheral insulin sensitivity. Since insulinemia was similar in normal and gestational diabetic pregnant women, we speculate that gestational diabetes is characterized by a higher peripheral insulin resistance, a fasting normal insulinemia and a higher hepatic insulin sensitivity, at least in other actions than on carbohydrate metabolism. The role of sex steroids, T4 and IGF-1 in regulating SHBG appears to be limited during pregnancy.     

Placental function test, clinical and biochemical parameters in diabetic pregnancy complicated by retinopathy

The pregnancy in specific-beta 1-glycoprotein (SP1) has been characterized as a beta 1 electrophoretic mobile glycoprotein with a molecular weight of 90,000 daltons. SP1 is known to be synthesized by the trophoblast. The measurement of this protein has been shown to be useful as a placental function test. At present, we have compared maternal SP1 serum levels in diabetic pregnancies between White classes A to D on the one hand and R, F on the other. A total of 37 uncomplicated pregnancies in healthy women and 32 of insulin-dependent pregnant diabetic women were examined between completed gestational weeks 8 and 41. In the diabetic group there were eleven women with diabetic retinopathy. Maternal SP1 serum levels were estimated by single radial immunodiffusion using a monospecific antiserum. In the results were integrated maternal and neonatal data such as glycemic control, glycosylated hemoglobin and insulin requirements. In each group there was a significant rise in maternal SP1 serum values in the second and the third trimester, when compared with values in the first trimester (p less than 0.01). Between the 34th and the 37th gestational week we found significantly lower SP1 values (p less than 0.05) in the retinopathic group (104.2 +/- 28.7 mg/l) in comparison with the control group (149.9 +/- 61.0 mg/l) and non-retinopathic group (139.1 +/- 41.7 mg/l).     

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.     

Metabolic control in diabetic pregnancy. Variations in plasma concentrations of glucose, free fatty acids, glycerol, ketone bodies, insulin, and human chorionic somatomammotropin during the last trimester.

Metabolic control was evaluated under standard conditions in pregnant gestational and insulin-dependent diabetic patients and control subjects from: (1) changes during an 8 hour period in blood glucose, free fatty acids (FFA), glycerol, ketone bodies, chorionic somatomammotropin (HCS), and insulin during the last trimester and (2) changes from weeks 32 to 40 in fasting blood glucose, FFA, glycerol, and ketone bodies. Mean glucose levels calculated from five daily analysis 28 days before delivery were determined in insulin-dependent and gestational diabetic patients (pregnancy glucose level). Group mean 8 hour glucose levels were similar in diabetic patients and control subjects, but glucose swings were greater in diabetic patients. Gestational diabetic patients had delayed insulin response following meals. FFA, glycerol, and ketone bodies varied in parallel with a simmilar pattern in diabetic patients and control subjects. Insulin-dependent diabetic patients had suppressed lipid mobilization in the afternoon when glucose levels were almost normal. In control subjects, FFA, glycerol, and ketone bodies were not above normal nonpregnant values. Diabetic patients showed great individual variations in all parameters measured. FFA and ketone bodies were significantly above normal; glycerol and glucose were normal. Pregnancy glucose levels were significantly correlated to a mean amplitude of glycemic swings (MAGE) determined from the 8 hour glucose profiles. The glucose value 2 hours after breakfast correlated best to the MAGE value.     

Continuous subcutaneous insulin therapy during early pregnancy

Intensive metabolic control of diabetes is probably important during formation of the embryo early in pregnancy. The purpose of this study was to determine the efficacy and complications of continuous subcutaneous insulin infusion therapy during the fifth to the tenth week of gestation. Twenty-four insulin-dependent subjects were trained to use blood glucose self-monitoring and the Auto Syringe portable insulin infusion pump (AS6C). Regular insulin was administered as a basal infusion of 18 +/- 8 U/24 hours (+/- SD) (12.2 +/- 3.9 mU . kg-1 . h-1) and as bolus injections of 6 +/- 3 U before meals and 1.2 +/- 1 U before snacks. Reasonable control of fasting (119 +/- 30 mg/dL) and postprandial (133 +/- 34 mg/dL) hyperglycemia was achieved, accompanied by an average of 2.2 +/- 1.5 symptomatic hypoglycemic episodes per week. The frequency of complications with this new therapy declined as the authors gained experience in teaching the system. The persistence of good diabetic control in many of the subjects after they returned to conventional insulin therapy points to the need for a controlled trial of continuous subcutaneous insulin infusion therapy versus intensive conventional therapy in pregnancy.     

Human placental insulin binding in normal and well-controlled diabetic patients

Previous studies of insulin binding to placentas of both insulin-dependent and untreated gestational diabetic patients have described placentas from diabetics to contain fewer insulin receptors than placentas from nondiabetic gravidas. However, these studies were done using membrane fractions prepared from the placentas and at a time when adequacy of antepartum glycemic control in the diabetic patients was not routinely evaluated by self blood sugar measurement or hemoglobin A1 assay. The current study compares specific 125I-insulin binding in vitro to intact placental villi from 15 normal patients with insulin binding to intact villi obtained from 15 insulin-dependent diabetic mothers whose fasting and postprandial blood sugars and hemoglobin A1 levels were maintained in a range normal for term pregnancy. We demonstrate that insulin binding to intact placental villi is the same in this group of diabetic patients as in the nondiabetic patients.     

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.     

Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes

We used the minimal model technique to obtain concurrent measurements of whole-body insulin sensitivity and pancreatic B-cell responsiveness to glucose during the third trimester of pregnancy. Insulin sensitivity in normal pregnant women (n = 8) was reduced to only one third that of a group of nonpregnant women (n = 7) of similar age and relative weight. This marked insulin resistance was compensated by reciprocal enhancement of the first and second-phase insulin responses to intravenous glucose, which were increased threefold as compared with the nonpregnant women. Women with gestational diabetes mellitus (n = 16) had mean insulin sensitivity that was similar to that of the normal pregnant group, which indicates that insulin action was appropriate for the late phase of pregnancy in the gestational diabetic group. By contrast, the mean first-phase insulin response was significantly reduced in women with gestational diabetes mellitus, as compared with that of normal pregnant women (p less than 0.001). However, approximately one fifth of the group with gestational diabetes mellitus had first-phase responses that did not fall below the 95% confidence interval for the mean in normal pregnant women. The mean second-phase response was also lower in the group with gestational diabetes, although the difference was of borderline statistical significance (p less than 0.09). Our findings reveal the quantitative nature of the reciprocal changes in insulin sensitivity and B-cell function that normally accompany late pregnancy. They further indicate that during the third trimester, mild gestational diabetes is characterized by an impairment of pancreatic B-cell function rather than an exaggeration of the normal insulin resistance of late pregnancy.     

Does impaired glucose tolerance imply a risk in pregnancy?

Of 218 pregnant women with abnormal glucose tolerance by the criteria of the World Health Organization (1985) 81.2% had impaired glucose tolerance and 18.8% gestational diabetes. Gestational diabetic women were of higher parity, more obese, required insulin therapy more often, had more babies weighing greater than 4 kg and had higher fasting plasma glucose than women with impaired glucose tolerance. Women with gestational impaired glucose tolerance were older, of higher parity, more obese and had heavier babies than pregnant women with a normal screening plasma glucose. Compared with women with impaired glucose tolerance, gestational diabetic women were more likely to have abnormality, and more severe impairment of their glucose tolerance test in the puerperium.