Gestational age alters fetal breathing response to intravenous insulin and intravenous glucose administration

An upward change in human maternal plasma glucose concentration is known to increase the percent of time spent in fetal breathing during the late third trimester of human pregnancy. We examined the fetal breathing effects of upward change in plasma glucose (after intravenous glucose administration) and downward change (after intravenous insulin administration) at two different times of day (8 AM and 4 PM) at both 24 and 36 weeks of gestation. No change in the percent of time spent in fetal breathing was seen after insulin infusion. Fetal breathing increased after glucose infusion at 36 weeks of gestation but not at 24 weeks. Responses did not differ between tests performed at 8 AM and 4 PM.     

Human fetal breathing response to intravenous glucose is directly related to gestational age

This prospective longitudinal study examined human fetal breathing activity over the second half of pregnancy both in the fasting state and after intravenous glucose administration. There was a linear relationship between gestational age and percent time spent breathing after glucose between 19 and 38 weeks' gestation. However, no such correlation could be demonstrated between gestational age and fetal breathing activity in the fasting state.     

Homeostatic indices of insulin resistance among gestational diabetics in anticipating pregnancy complications

Abstract

Objective: This was to determine HOMA-IR score as well as to assess its association in fetal and maternal outcomes among pregnant women with diabetes risks.

Methods: A prospective cohort study of pregnant women with diabetes risks was done. GDM was diagnosed using modified glucose tolerance test. Serum insulin was taken and measured by an electrochemiluminescence immunoassay method. Plasma glucose was measured by enzymatic reference method with hexokinase. HOMA-IR score was calculated for each patient. Maternal and fetal outcomes were analyzed.

Results: From 279 women recruited, 22.6% had GDM with higher HOMA-IR score (4.07?±?2.44 versus 2.08?±?1.12; p?=?0.001) and fasting insulin (16.76?±?8.63?µIU/L versus 10.15?±?5.07?µIU/L; p?=?0.001). Area under ROC curve for HOMA-IR score was 0.79 (95% confidence interval, 0.74–0.84) with optimum cut-off value of 2.92 (sensitivity?=?63.5%; specificity?=?89.8%), higher than recommended by IDF (2.38). This point showed significant association with neonatal hypoglycemia (p?=?0.02) and Cesarean section (p?=?0.04) in GDM mothers.

Conclusions: HOMA-IR score and insulin resistance levels were higher in GDM women in our population. With the cut-off HOMA-IR value of 2.92, neonatal hypoglycemia and Cesarean section were significant complications in GDM mothers. This can be used in anticipation of maternal and fetal morbidities.     

Gestational diabetes reverses the circadian variation of plasma insulin response to intravenous glucose

Both healthy third-trimester pregnant women and a group of women with gestational diabetes failed to show a difference in glucose clearance rates when given an intravenous glucose bolus at 8 AM compared with 4 PM. The plasma insulin response in the healthy pregnant women was greater at 8 AM. In the diabetic group, the peak insulin response was greater at 4 PM, but it was more prolonged after the 8 AM tests. These alterations in plasma insulin response were especially striking in the subgroup of obese women with gestational diabetes, who demonstrated metabolic differences compared with their nonobese counterparts.     

Continuous subcutaneous insulin infusion. Improved blood glucose in pregnant diabetics

The effect of continuous subcutaneous insulin infusion (c.s.i.i.) on the control of blood-glucose concentration and outcome of pregnancy was assessed in two pregnant diabetics (class B and class C White classification) who were poorly controlled with conventional insulin therapy. The insulin pump was carried in a holster and enabled the patients to ambulate freely. The patients were able to refill the syringe, to augment the infusion rate at mealtime and to change the implantation site of the needle weekly, and thus, were able to leave the hospital. Daily glucose profiles were assessed 1-3 times a week, and the infusion rate was readjusted accordingly. Twenty-four hours glucose profiles were obtained from both patients during inpatient conventional insulin regimens, and then, during c.s.i.i. which was maintained for 41 and 145 days, respectively. Mean 24 hours glucose concentrations were reduced from 156 to 113 mg/100 ml, mean fasting glucose from 152 to 106 mg/100 ml, and mean diurnal variation (maximal excursion) from 75 to 65 mg/100 ml. The favourable results achieved with the c.s.i.i. enabled both patients to reach the 18th week of gestation and to deliver healthy non-macrosomic infants, who had uneventful and morbid-free neonatal periods. Since the c.s.i.i. supplies insulin in a more physiological manner than twice daily regimens, better control of blood sugar and body fuel metabolism may be achieved. By extending the therapy to the early stages of pregnancy, or if possible to pre-conceptional period, reduced perinatal mortality and morbidity may be anticipated.     

Comparison of glyburide and insulin for the management of gestational diabetics with markedly elevated oral glucose challenge test and fasting hyperglycemia.

OBJECTIVE: To compare the effectiveness of glyburide and insulin for the treatment of Gestational diabetes mellitus (GDM) in women who had OGCT >or=200 mg/dl and fasting hyperglycemia. STUDY DESIGN: A retrospective study was performed among a subset of women treated with glyburide or insulin for GDM from 1999 to 2002 with an OGCT >or=200 mg/dl and pretreatment fasting plasma glucose >or=105 mg/dl. Exclusion criteria included pretreatment fasting >or=140 mg/dl, gestational age >or=34 weeks and multiple gestation. Maternal and neonatal outcomes were assessed. Statistical methods included bivariate and multivariable logistic regression analyses. RESULTS: In 1999 to 2000, 78 women were treated with insulin; in 2001 to 2002, 44 of 69 (64%) received glyburide. There were no statistically significant differences between the two groups with regards to mean OGCT (230+/-25 vs 223+/-23 mg/dl, P=0.07) and mean pretreatment fasting (120+/-10 vs 119+/-11 mg/dl, P=0.45). Seven women (16%) failed glyburide. Women in the insulin group were younger (31.5+/-5.8 vs 35.2+/-4.7 years, P<0.001) and had a higher mean BMI (32.4+/-6.4 vs 29.1+/-5.8 kg/m(2), P=0.003) compared to glyburide group. There were no significant differences in birth weight (3524+/-548 vs 3420+/-786 g, P=0.65), macrosomia (19 vs 23%, P=0.65), pre-eclampsia (12 vs 11%, P=0.98) or cesarean delivery (39 vs 46%, P=0.45). Neonates in the glyburide group were diagnosed more frequently with hypoglycemia (34 vs 14%, P=0.01). When controlled for confounders, macrosomia was found to be associated with glyburide treatment (OR 3.5, 95% CI 1.1 to 11.4). CONCLUSION: In women with GDM who had a markedly elevated OGCT and fasting hyperglycemia, glyburide achieved similar birth weights and delivery outcomes but was associated with an increased risk of macrosomia. The possible increased risk of neonatal hypoglycemia in the glyburide group warrants further investigation.     

Fructosamine in relation to maternofetal glucose and insulin homeostasis in gestational diabetes

Summary The problem in screening for gestational diabetes is recognizing fetuses endangered by hyperinsulinism. 21.8% of patients with gestational diabetes (defined as a glucose peak exceeding 160 mg/dl after an oral glucose load of 1 g per kg body weight) develop fetal hyperinsulinism. Thus, is indicated by an elevated amniotic fluid insulin (AFI) concentration and requires insulin treatment. Since fetal hyperinsulinism can be neither predicted nor ruled out by single parameters of materal metabolism, every patient with gestational diabetes had to undergo amniocentesis for amniotic fluid analysis. In 110 gestational diabetics and 822 controls, fetal hyperinsulinism was predicted by the combination of the oGTT (≥160 mg/dl) and maternal serum fructosamine (≥2.6 mmol/l) with a sensitivity of 95.8% and a specificity of 91.8%. Thus, 73% of gestational diabetics need not undergo amniocentesis. With a sensitivity of 20.8%, the combination of the oGTT and HbA1c is not useful in identifying hyperinsulinemic fetuses.     

妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖关系的研究

目的　探讨妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖的关系。方法　采用放射免疫法 ,测定 36例妊娠期糖代谢异常孕妇 (糖代谢异常组 )和 2 4例正常孕妇 (正常妊娠组 )的空腹及口服 50g葡萄糖后 3h的血清瘦素水平 ;采用电化学发光法测定两组孕妇的空腹血清胰岛素水平 ;采用低压液相色谱分析法测定两组孕妇的糖化血红蛋白 ;采用葡萄糖氧化酶法测定两组孕妇的口服 50g葡萄糖后 1h的血糖水平。结果　 (1 )糖代谢异常组孕妇血清瘦素水平为 (1 4 9± 4 3) μg/L ,正常妊娠组为 (1 0 0± 1 8) μg/L ,两组比较 ,差异有极显著性 (P <0 0 1 ) ;(2 )糖代谢异常组孕妇空腹血清胰岛素、糖化血红蛋白、服糖后 1h血糖水平分别为 (1 2 9± 4 3)mU/L、 (6 1± 1 1 ) %、(1 1 0±1 4)mmol/L ;正常妊娠组孕妇分别为 (8 6± 3 2 )mU/L、(4 5± 1 0 ) %、(7 8± 1 2 )mmol/L。糖代谢异常组孕妇血清瘦素水平与空腹血清胰岛素、糖化血红蛋白、服糖后 1h的血糖水平呈明显的正相关关系 ,相关系数 (r)分别为 0 835、0 758、0 561。结论　妊娠期糖代谢异常孕妇空腹血清瘦素水平升高 ,其瘦素水平的高低与空腹血清胰岛素及血糖水平相关     

Prophylactic insulin in gestational diabetes

Patients with gestational diabetes were divided into two groups according to the results of three-hour oral glucose tolerance tests. Those with fasting euglycemia (serum glucose 95 mg/dL or lower) on oral glucose tolerance test (class A) were treated with diet alone, whereas those with fasting hyperglycemia on oral glucose tolerance test (class A/B) were treated with both diet and insulin (15 U neutral protamine Hagedorn insulin before breakfast). The frequency of macrosomia (birth weight more than 4000 g) among class A/B gestational diabetics was 16.2%, which was significantly greater than the 5.6% incidence in class A diabetics and the 6.4% incidence in controls. After controlling for potential confounding risk factors, it was determined that class A diabetics had a frequency of macrosomia no different from that of nondiabetics. Nonobese gestational diabetics with fasting hyperglycemia (class A/Bs), who were treated with diet and prophylactic insulin, also had a frequency of macrosomia no different from that of nondiabetics or class A diabetics. However, the diet and insulin regimen did not prevent excess macrosomia in class A/B diabetics who were obese.     

Acute effect of exercise on blood glucose and insulin levels in women with gestational diabetes

OBJECTIVE: To evaluate the effect of a single session of exercise (cycling), at rest (control condition) and at two intensity levels (low- and moderate-intensity exercise conditions), on blood glucose and insulin in pregnancy complicated by gestational diabetes mellitus (GDM). METHODS: A one-group repeated measures design was used. Women aged 18-38 with GDM, no other complications, not on insulin, and not exercising regularly were recruited. The women rested or exercised at the two intensities for 30 min and rested for 2 h after each session. Blood was sampled for blood glucose, insulin and hematocrit at baseline and every 15 min. RESULTS: There was no difference at baseline in blood glucose levels. The blood glucose level was significantly lower for each exercise condition compared to rest, and for moderate compared to low-intensity exercise (5.2 vs. 4.3 vs 3.9 mmol/l) at the end of exercise (30 min), and for the two exercise conditions compared to rest at 15 min after exercise (4.9 vs 4.4 vs. 4.0 mmol/l). By 45 min after exercise, the blood glucose values were nearly identical. The area under the curve for blood glucose was significantly lower for low- and moderate-intensity exercise than for rest (p = 0.01). The slope of change in insulin among the three conditions, from baseline to the 30-min session, approached significance (p = 0.065). The power for that analysis was 0.51. A sample of 23 would have been required to increase the power to 0.80. CONCLUSIONS: Significant declines in blood glucose level were observed during low- and moderate-intensity exercise compared to rest. These differences were gone by 45 min after exercise. Continued research should examine those with high body mass index and more pronounced hyperglycemia for further evaluation of the effect of exercise on blood glucose and insulin levels in women with GDM.     

Acute effect of exercise on blood glucose and insulin levels in women with gestational diabetes

Objective : To evaluate the effect of a single session of exercise (cycling), at rest (control condition) and at two intensity levels (low- and moderate-intensity exercise conditions), on blood glucose and insulin in pregnancy complicated by gestational diabetes mellitus (GDM). Methods : A one-group repeated measures design was used. Women aged 18-38 with GDM, no other complications, not on insulin, and not exercising regularly were recruited. The women rested or exercised at the two intensities for 30 min and rested for 2 h after each session. Blood was sampled for blood glucose, insulin and hematocrit at baseline and every 15 min. Results : There was no difference at baseline in blood glucose levels. The blood glucose level was significantly lower for each exercise condition compared to rest, and for moderate compared to low-intensity exercise (5.2 vs. 4.3 vs 3.9 mmol/l) at the end of exercise (30 min), and for the two exercise conditions compared to rest at 15 min after exercise (4.9 vs 4.4 vs. 4.0 mmol/l). By 45 min after exercise, the blood glucose values were nearly identical. The area under the curve for blood glucose was significantly lower for low- and moderate-intensity exercise than for rest ( p = 0.01). The slope of change in insulin among the three conditions, from baseline to the 30-min session, approached significance ( p = 0.065). The power for that analysis was 0.51. A sample of 23 would have been required to increase the power to 0.80. Conclusions : Significant declines in blood glucose level were observed during low- and moderate-intensity exercise compared to rest. These differences were gone by 45 min after exercise. Continued research should examine those with high body mass index and more pronounced hyperglycemia for further evaluation of the effect of exercise on blood glucose and insulin levels in women with GDM.     

Glucose and free fatty acid response to intravenous glucose during pregnancy

Intravenous glucose tolerance tests were performed in undernourished and well-nourished normal pregnant women and for toxemic women near term. Both blood glucose and free fatty acid levels were analyzed, till 90 min after glucose load. The results suggested that glucose response to intravenous load was poor both in normal undernourished and toxemic women as compared to well-nourished women. However, the free fatty acid pattern was abnormal only in toxemic women in that the levels free fatty acid levels were analyzed, till 90 min after glucose load. The results suggested that glucose response to intravenous load was poor both in normal undernourished and toxemic women as compared to well-nourished women. However, the free fatty acid pattern was abnormal only in toxemic women in that the levels free fatty acid levels were analyzed, till 90 min after glucose load. The results suggested that glucose response to intravenous load was poor both in normal undernourished and toxemic women as compared to well-nourished women. However, the free fatty acid pattern was abnormal only in toxemic women in that the levels did not return to basal value even after 90 min of glucose load. Since human placental lactogen in pregnancy is known to regulate free fatty acid release for energy utilization, its deficiency in toxemia (commonly known to occur) could be implicated in the abnormal free fatty acid response seen in this investigation.     

Glyburide metabolism by placentas of healthy and gestational diabetics

The aim of this investigation was to determine the metabolism of glyburide (GL) by microsomes prepared from placentas obtained from uncomplicated pregnancies (UP), women with gestational diabetics (GD) on a diabetic diet, and those on a diet and GL. Term placentas were obtained from UP and GD. Crude microsomal fractions were prepared by differential centrifugation and stored at -80 degrees C. The activity of the microsomes in metabolizing glyburide to the trans-4-hydroxycyclohexyl glyburide (THCGL) and cis-3-hydroxycyclohexyl glyburide (CHCGL) was determined and quantified using high-performance liquid chromatography-mass spectrometer (HPLC-MS). The activity of the placental microsomes varied widely between individual placentas in each group. The median values (pmol.mg (-1) P.min (-1)) for the rates of THCGL formation were 0.34, 0.3, and 0.23 for placentas of UP, GD on diet, and GD on GL and a diet, respectively. The median values for CHCGL formation were 0.13 for UP, 0.11 for GD on a diet, and 0.10 (pmol.mg (-1) P.min (-1)) for GD on GL and a diet. A pool of individual microsomal fractions from each group was prepared and its activity revealed the following: greater formation of THCGL in the UP (0.36 +/- 0.10) than GD (0.22 +/- 0.03) ( P = 0.058 for GD on a diet, 0.04 for GD on GL). There was greater formation of CHCGL in UP (0.26 +/- 0.04) than GD (0.12 +/- 0.003) ( P < 0.006). There was no difference in GD on a diet and GD on GL plus diet. We concluded that the apparent differences in the formation of metabolites may be statistically significant, but it is unlikely to be of physiological importance, given the sample size and other experimental factors. Therefore, a more comprehensive investigation is underway.     

Androgen and insulin response to an oral glucose challenge in hyperandrogenic women

To further investigate the relationship between insulin and androgen secretion in hyperandrogenic women, the authors measured the response of serum insulin and androgen concentrations to an 8 A.M. oral glucose tolerance test (OGTT) in ten hyperandrogenic (HA) women and seven midfollicular phase control subjects. Significant positive correlations were demonstrated between fasting serum insulin concentration and both androstenedione (delta 4A) and testosterone (T) concentrations, which were independent of body mass index (kg/m2). A strong negative correlation was demonstrated between fasting insulin and dehydroepiandrosterone sulfate (DHEAS) levels within the HA group (r = -0.84, P = 0.003). Significant positive correlations were also demonstrated between the cumulative sum insulin response during OGTT and the percent change from fasting baseline to 3 hours in serum delta 4A (r = 0.65, P = 0.006), T (r = 0.51, P = 0.033), and dihydrotestosterone (DHT) concentrations (r = 0.75, P less than 0.001). Our data suggests that abnormalities in insulin secretion are common in HA women and that there is a strong correlation between changes in serum concentrations of insulin and androgens during an OGTT.     

Plasma visfatin levels in pregnant women with normal glucose tolerance,gestational diabetes and pre-gestational diabetes mellitus

Objective.?Visfatin, an adipocytokine, is a peptide predominantly expressed in and secreted from visceral adipose. In this study, we aimed to compare visfatin levels in gestational (GDM) and pre-gestational diabetic (pre-GDM) women with healthy pregnant women. We also sought to determine whether there was a correlation between visfatin levels and serum glucose levels at 1?h after the 50-g oral glucose challenge test in pregnant women with GDM and normal glucose tolerance.

Methods.?The study consisted of 65 pregnant women: 21 patients with GDM (Group 1), 20 patients with pre-GDM (Group 2) and 24 gestational age and BMI-matched healthy pregnant women (Group 3) were enrolled.

Results.?Plasma visfatin levels in Groups 1 and 2 were significantly higher than in Group 3 (P?<?0.001). Plasma visfatin levels in Groups 1 and 2 were similar (P?>?0.05). There was no significant correlation between visfatin levels and serum glucose levels at 1?h after the glucose tolerance test in both Groups 1 and 3 (P?>?0.05).

Conclusions.?Our results support the literature indicating higher visfatin levels in women with GDM compared to women with normal glucose tolerance. Interestingly, we found similarly high visfatin levels in women with pre-GDM.     

Placental glucose transport in gestational diabetes mellitus

OBJECTIVE: We have previously reported that type 1 diabetes mellitus with hyperglycemia during the first trimester is associated with an up-regulation of placental glucose transport at term. We speculated that glucose concentrations regulate placental glucose transporters only during early pregnancy. To test this hypothesis we studied placental glucose transport in gestational diabetes mellitus, which is associated with hyperglycemia mainly during the second half of pregnancy. STUDY DESIGN: Syncytiotrophoblast microvillous membrane vesicles and basal membrane vesicles were isolated from uneventful pregnancies (control group, n = 32) and pregnancies complicated by gestational diabetes mellitus (n = 18). Glucose uptake and glucose transporter 1 expression were studied by means of radiolabeled tracers and Western blotting, respectively. RESULTS: Gestational diabetes mellitus was not associated with alterations in placental glucose transport. Separate analysis of 6 patients in the gestational diabetes mellitus group with large-for-gestational-age babies did not affect these results. CONCLUSION: These findings are consistent with the hypothesis that the sensitivity of placental glucose transporters to regulation by nutrient availability is limited to early pregnancy.     

Fetal and maternal blood glucose, insulin and acid base observations following maternal glucose infusion.

The aim of the present investigation was to examine the fetal and maternal blood glucose and insulin response following glucose infusion to the mother. The studies were performed on 11 primigravid patients with a gestational age of 38-40 weeks during the first stage of labor. Glucose was given intravenously by a bolus injection of 330 mg/kg body weight, followed by a glucose infusion of 27.5 mg/kg/min for 60 min. Glucose concentration, immuno-reactive insulin (IRI), pH and base excess of the maternal and fetal blood were measured before and during maternal glucose load. Maternal blood glucose rose within 10 min. up to 280.0 mg% (SD 25.9). This level could be fairly maintained throughout the experiment. The maternal glucose was after 60 min. infusion 326.5 mg% (SD 46.9). Fetal glucose concentration rose continuously from 65.8 mg% (SD 5.8) at control to 249.2 mg% (SD 23.3) after 60 min. The increase of maternal and fetal glucose was associated with an elevation of immuno-reactive insulin (IRI). The maternal insulin was 24.0 micronU/ml (SD 8.0). It was scattered over a wide range (55.4 micronU/ml-217.1 micronU/ml) after 60 min. glucose infusion. The fetal insulin was 17.0 micronU/ml (SD 5.2) at control and rose by 86.5% (SD 80.5) after 60 min. glucose load. One case of a mother with a subclinical diabetes mellitus deviated where the fetal insulin rose from 26.0 micronU/ml at control to 215.6 micronU/ml after 60 min. infusion. The increase of insulin per glucose rise was correlated to fetal body weight. During glucose infusion to the mother of both, fetal and maternal, acid base parameters remained unchanged. From these observations it may be concluded that in the human fetus insulin secretion following a single glucose load is generally low, however, it increases in cases where the maternal insulin response to glucose load is abnormal. This might be related to a chronic stimulation by glucose of the fetal pancreatic islet cells in poorly controlled diabetic and possibly prediabetic patients.