Disorders in Glucidic Metabolism and Congenital Heart Diseases: Detection and Prevention

The identification of gestational diabetes (GDM) through appropriate screening and its subsequent treatment have not been demonstrated to limit neonatal malformations to date. This study aimed to detect congenital heart diseases in newborns of mothers with GDM by evaluating the existence of a correlation with maternal glycemic control. This observational prospective study investigated newborns of mothers with GDM enrolled during a period of 9 months. Four subgroups were considered according to the type of maternal glucidic alteration during pregnancy and the home treatment: impaired glucose tolerance, insulin-dependent gestational diabetes mellitus (IDDM), non-insulin-dependent gestational diabetes mellitus (NIDDM), and gestational diabetes not controlled (NC: untreated diabetes). Student’s t test was used to compare the subgroups. The study enrolled 65 newborns (30 boys) born to 82 of mothers with impaired glucidic metabolism. Patent ductus arteriosus was observed in 11 patients (16.9 %), pulmonary stenosis of mild grade in 4 patients ( 6.2 %), and hypertrophy of the ventricular septum in 22 patients (33.8 %). A total of 14 patients had increased thickness in the left ventricle posterior wall, and 17 patients had an abnormal electrocardiogram. Hyperglycemia can influence the development of the fetal heart, affecting both its structure and its function. A treatment with insulin for women with GDM is supported by the study data.     

Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born to mothers in the ACHOIS randomised controlled trial

Background  

Mild gestational diabetes is a common complication of pregnancy, affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries, such as shoulder dystocia, bone fractures and nerve palsies. This study aimed to compare the plasma glucose concentrations and serum insulin, leptin and adiponectin in cord blood of babies of women (a) without gestational diabetes mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with treatment.     

妊娠糖尿病母亲儿激素水平的变化

妊娠期糖尿病(gestational diabetes mellitus,GDM)的发病率逐年上升,既往认为糖尿病母亲儿的异常主要由宫内高血糖引起,越来越多的研究发现即使GDM孕妇血糖控制较好,仍易分娩巨大儿及出现围生期并发症,目前普遍认为与某些激素的异常分泌有关.大量研究表明妊娠期糖尿病母亲儿的多种激素水平均发生了改...     

Psychomotor development in the children of mothers with type 1 diabetes mellitus or gestational diabetes mellitus

The purpose of this study was to examine psychomotor development in children born to mothers with type 1 diabetes mellitus (DM1) or gestational diabetes mellitus (GDM). The influence of metabolic control in pregnant diabetic mothers and complications during labor on their children's psychological and physical development was evaluated. The analysis included 59 children, 20 of mothers with GDM, 19 of mothers with DM1, and 20 children of healthy mothers. Clinical observations and medical history were recorded and children were assessed using the Brunet-Lezine Psychomotor Development Scale. Abnormalities were found more often in the children of mothers with DM1 whose illness was insufficiently controlled during pregnancy and of mothers with serious hypoglycemia while pregnant. Speech, eye-movement coordination and social aspects were affected.     

Obesity, gestational diabetes and pregnancy outcome

The prevalence of both obesity and gestational diabetes mellitus (GDM) is rising worldwide. The complications of diabetes affecting the mother and fetus are well known. Maternal complications include preterm labor, pre-eclampsia, nephropathy, birth trauma, cesarean section, and postoperative wound complications, among others. Fetal complications include fetal wastage from early pregnancy loss or congenital anomalies, macrosomia, shoulder dystocia, stillbirth, growth restriction, and hypoglycemia, among others. The presence of obesity among diabetic patients compounds these complications. The above-mentioned short-term complications can be mediated by achieving the desired level of glycemic control during pregnancy. However, GDM during pregnancy is associated with increased risk of early obesity, type 2 diabetes during adolescence and the development of metabolic syndrome in early childhood. Additionally, GDM is a marker for the development of overt type 2 diabetes and metabolic syndrome for the mother in the early future.     

Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) mice

Infant macrosomia is a classic feature of a gestational diabetes mellitus (GDM) pregnancy and is associated with increased risk of adult obesity and type II diabetes mellitus, however mechanisms linking GDM and later disease remain poorly understood. The heterozygous leptin receptor-deficient (Lepr(db/+)) mouse develops spontaneous GDM and the fetuses display characteristics similar to infants of GDM mothers. We examined the effects of GDM on maternal insulin resistance, fetal growth, and postnatal development of hepatic insulin resistance. Fetal body weight on d 18 of gestation was 6.5% greater (p < 0.05) in pups from ad libitum-fed db/+ mothers compared with wild-type (WT) controls. Pair-feeding db/+ mothers to the intake of WT mothers normalized fetal weight despite less than normal maternal insulin sensitivity. More stringent caloric restriction reduced insulin and glucose levels below WT controls and resulted in fetal intrauterine growth restriction. The level of hepatic insulin receptor protein was decreased by 28% to 31% in both intrauterine growth restriction and fetuses from ad libitum-fed GDM mothers compared with offspring from WT mothers. In 24-wk-old adult offspring from GDM mothers, body weight was similar to WT offspring, however, the females from GDM mothers were fatter and hyperinsulinemic compared with offspring from WT mothers. Insulin-stimulated phosphorylation of Akt, a key intermediate in insulin signaling, was severely decreased in the livers of adult GDM offspring. Hepatic glucose-6-phosphatase activity was also inappropriately increased in the adult offspring from GDM mothers. These results suggest that spontaneous GDM in the pregnant Lepr(db/+) mouse is triggered by overfeeding, and this effect results in obesity and insulin resistance in the livers of the adult offspring. The specific decrease in Akt phosphorylation in livers of adult offspring suggests that this may be a mechanism for reduced insulin-dependent physiologic events, such as suppression of hepatic glucose production, a defect associated with susceptibility to type II diabetes mellitus.     

妊娠期糖耐量异常对新生儿的影响

目的：妊娠期糖代谢异常可引起新生儿多种并发症。该文通过回顾性分析,探讨妊娠期不同程度糖代谢异常对新生儿的影响。方法：根据孕妇在孕24～28周时50 g葡萄糖筛查试验(GCT)及75 g葡萄糖耐量试验(OGTT)的结果,将其所分娩新生儿分为4组：妊娠期糖尿病组(GDM,182例)、妊娠期糖耐量减低(GIGT)1 h组(57例)、GIGT (2~3 h)组(156例)、GCT异常而OGTT正常(仅GCT异常组, 38例),并以糖代谢正常孕妇所分娩新生儿1 025例作为对照,对妊娠期不同程度糖代谢异常孕母的围产儿结局进行比较。结果：GIGT（1 h）组巨大儿、大于胎龄儿及小于胎龄儿发生率,以及低血糖、早产发生率明显高于对照组,与GDM组类似。GIGT（2~3 h）组和仅GCT异常组巨大儿、小于胎龄儿以及低血糖和早产的发生率明显低于GDM组,差异均有显著性意义,与对照组比较差异无显著性意义。GIGT(1 h)组新生儿低血糖和早产发生率明显高于GIGT (2~3 h) 组和仅GCT异常组, 差异有显著性意义。结论：母亲妊娠期糖代谢异常程度不同对新生儿的影响不同。孕母OGTT 试验1 h 单项血糖升高的糖耐量减低与妊娠糖尿病一样对新生儿具有危险性,可导致巨大儿、大于胎龄儿、小于胎龄儿及低血糖、早产的发生率增加。［中国当代儿科杂志,2009,11（3）：177-180］     

Association between maternal pre-existing or gestational diabetes and health problems in children

There is general consensus that children of women with pre-existing diabetes mellitus (PDM) have an increased risk of malformations and neurodevelopmental problems. Whether this is also true for children of women with gestational diabetes mellitus (GDM) is a matter of debate. This study investigated inpatient hospital care up to 10 y of age of children born to GDM and PDM women as a rough estimate of child morbidity. Hospital care of children born to 82 684 GDM women, 3874 PDM women and 1213957 controls was compared by linking the Swedish Medical Birth Registry with the Hospital Discharge Registry. Similar comparisons were performed in a local well-controlled group of 326 children born to GDM women in the Lund area. Children of PDM women and to a lesser degree children of GDM women had a statistically significant increase in hospitalizations, evident at least up to 10 y of age. Significantly increased risks of hospitalization were found for neurological/developmental disorders [odds ratio (OR) 2.30 and 1.36 for PDM and GDM, respectively)], malformations (OR 2.05 and 1.23), infections (OR 1.56 and 1.20) and accidents (OR 1.32 and 1.14). Conclusion: The high hospitalization rates of these children indicate an increased morbidity, including neurodevelopmental disorders.     

Gestational diabetes and offspring body disproportion

Aim:  It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants.
Methods:  Birth characteristics of 884 267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed.
Results:  The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41–4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus.
Conclusion:  Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.     

Gestational diabetes mellitus--implications of different treatment protocols

OBJECTIVE: To assess the impact of different management approaches to gestational diabetes mellitus (GDM) on perinatal outcome. PATIENTS AND METHODS: The study group consisted of 2,060 patients with GDM treated in our center from January 1980 through December 1999. Four time periods were defined on the basis of changes in treatment protocols. Perinatal complications were compared between the periods and with normal pregnancy controls. RESULTS: The last two periods (1993-1999) were characterized by lower mean glucose level, lower mean gestational age at delivery, and a decline in macrosomia, shoulder dystocia and perinatal mortality rates, but also by high rates of labor induction and Cesarean delivery. A significant difference was found between the GDM and normal control groups in rates of labor induction (38.6% vs 10.8%, p < 0.001) and Cesarean delivery (34% vs 20%, p < 0.001) for the last period. CONCLUSIONS: Perinatal complications are preventable with good glycemic control and early induction of labor, but at a cost of a higher Cesarean section rate.     

Long-term effects of diabetes during pregnancy on the offspring

Background: Many epidemiological and experimental studies have proven that some adult diseases might have their origin in fetal life. It has been also hypothesized that intra-uterine environment in pregnancy complicated with diabetes might influence the development of obesity, type 2 diabetes, and cardiovascular diseases in the offspring.
Objectives: To assess glucose metabolism, insulin secretion, and prevalence of obesity in the offspring of mothers with pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) and to evaluate the relationship between maternal metabolic control during pregnancy and metabolic disturbances in children.
Subjects: Children of mothers with PGDM (n = 43) and GDM (n = 34) were examined at 4–9 yr of age and compared with the control group (n = 108; metabolic parameters available for n = 29).
Methods: The incidence of overweight and obesity, impaired glucose tolerance, and insulin resistance were analyzed based on anthropometric and biochemical measurements. Statistical analysis was performed with statistica package.
Results: In children of GDM mothers, body mass index z-score (0.81 ± 1.01 vs. −0.04 ± 1.42 PGDM vs. 0.07 ± 1.28 control group) and insulin resistance indices (homeostasis model assessment index – insulin resistance 1.112 vs. 0.943 PGDM vs. 0.749 control group) were significantly higher than in other groups. Obesity and insulin resistance were also most frequent in GDM group [not significant (NS)]. In addition, we observed the relationship between maternal hemoglobin A1c and mean glycemia in perinatal period and insulin resistance in children. There was not such correlation for the class of maternal diabetes.
Conclusion: Children born to mothers with gestational diabetes seem to be at risk for obesity and metabolic disturbances.     

Father's weight could contribute to large babies in overweight and obese mothers with and without gestational diabetes

We evaluated whether there was an association between fathers’ nutritional status and children's birth weight (BW) considering weight-matched mothers with and without gestational diabetes mellitus (GDM). In total, 86 trios of women, infants, and fathers were evaluated. BW was not different between the groups of obese and non-obese parents, frequency of maternal obesity, or GDM. The percentage of infants who were large for gestational age (LGA) was 25% in the obese group and 14% in the non-obese group (p = 0.44). There was a borderline significance for higher body mass index (p = 0.09) of the father in the LGA group compared with the adequate for gestational age group. These results corroborate the hypothesis that the father's weight can also be relevant for the occurrence of LGA.     

Beta Testing of a Gestational Diabetes Risk Reduction Intervention for American Indian and Alaska Native Teens

IntroductionAmerican Indian and Alaska Native (AIAN) girls have double the risk of obesity, pregnancy, and gestational diabetes mellitus (GDM) than the general U.S. population. The purpose of this study was to beta test Stopping GDM (SGDM), a GDM risk reduction intervention for at-risk AIAN teens, before beginning a randomized controlled trial.MethodA sample of 11 AIAN mothers and daughters were recruited through an urban Indian health program. Daughters were at risk of GDM as assessed by a BMI ≥ 85th percentile. Pre- and posttest online questionnaires evaluated the online intervention (e-book and video).ResultsMean pre- to posttest knowledge increased for mothers and daughters on diabetes prevention, reproductive health, and GDM knowledge. Daughters demonstrated an increased self-efficacy for healthy living and pregnancy planning. Satisfaction for the e-book, video, and online survey was moderately high to very high.DiscussionThe SGDM intervention is feasible and acceptable in AIAN mother–daughter dyads. These findings informed the SGDM intervention and the randomized controlled trial evaluation protocol.     

Maternal nutritional status, diabetes and risk of macrosomia among Native Canadian women

Multivariate methods were used to identify risk factors for macrosomia (birth weight >4000 g) among 741 singleton births to Native Canadian women from Sioux Lookout Zone, Ontario, Canada, in 1990–1993. The average birth weight was 3691±577 g, and 29.2% of infants weighed more than 4000 g at birth. Macrosomic infants were born at later gestational ages and were more likely to be male. Women delivering macrosomic infants were taller, entered pregnancy with higher body mass indexes (BMI) and gained more weight during pregnancy, but were less likely to smoke cigarettes. They were more likely to have previously delivered a macrosomic infant and to have had gestational diabetes mellitus (GDM). Risk of macrosomia was associated with maternal glycemic status; women with pre-existing diabetes were at greatest risk, followed by those with GDM A₂ (fasting glucose ≥6 mmol/l). Women with GDM A₁ (fasting glucose <6 mmol/l) were not at increased risk for delivering a macrosomic infant, but glucose-tolerant women with high glucose concentrations 1 h after the 50 g challenge were at somewhat increased risk. Maternal glycemic status and maternal nutritional status before and during pregnancy are important determinants of macrosomia in this native population.     

Accelerated starvation in pregnancy: implications for dietary treatment of obesity and gestational diabetes mellitus

The biological significance of ketonemia of brief duration and moderate proportions during pregnancy remains uncertain. Thus, controversy persists about whether caloric restriction for obese women during pregnancy, particularly when the obesity is complicated by gestational diabetes mellitus (GDM), constitutes appropriate therapy. We have demonstrated, in a rigorously controlled setting using a Clinical Research Center, that all of the features of 'accelerated starvation' become manifest after 14 h and before 18 h of dietary deprivation. Women with GDM exhibit the same capacity for early 'accelerated starvation' as in normal pregnancy; thus, their insulin deficiency and insulin resistance do not appear to be sufficient to render them increasedly at risk for uncontrolled catabolism. Some cautious exploration of the use of hypocaloric diets as a therapeutic approach to the metabolic disturbances of GDM may be justified.     

Neonatal Macrosomia and Hypoglycaemia in Children of Mothers with Insulin-Treated Gestational Diabetes Mellitus

ABSTRACT. All newborn children to mothers with gestational diabetes mellitus (GDM) in the county of Örebro were investigated during a one year prospective study. Neonatal macrosomia (birthweight > 3 SD) was observed in 27% of children of mothers with GDM and was significantly correlated to the cord C-peptide concentration. Hypoglycaemia (B-glucose <1.5 mmol/l) was observed in 38% of the children, most frequently two hours after delivery. Hypoglycaemia was not more common in macrosomic children and could not be predicted by the blood glucose concentration of the mother at delivery or by the cord C-peptide level. It is concluded that mothers with GDM must be intensively treated in order to avoid the occurrence of macrosomia in their infants and that the newborn child must be carefully observed and treated in order to avoid neonatal hypoglycaemia.     

Neonatal macrosomia and hypoglycaemia in children of mothers with insulin-treated gestational diabetes mellitus.

All newborn children to mothers with gestational diabetes mellitus (GDM) in the county of Orebro were investigated during a one year prospective study. Neonatal macrosomia (birthweight greater than 3 SD) was observed in 27% of children of mothers with GDM and was significantly correlated to the cord C-peptide concentration. Hypoglycaemia (B-glucose less than 1.5 mmol/l) was observed in 38% of the children, most frequently two hours after delivery. Hypoglycaemia was not more common in macrosomic children and could not be predicted by the blood glucose concentration of the mother at delivery or by the cord C-peptide level. It is concluded that mothers with GDM must be intensively treated in order to avoid the occurrence of macrosomia in their infants and that the newborn child must be carefully observed and treated in order to avoid neonatal hypoglycaemia.     

Postnatal changes in concentrations of free and bound leptin

AIM: To evaluate the effect of maternal diabetes on the concentrations of free and bound leptin at birth and during postnatal adaptation. METHODS: Total, bound, and free leptin concentrations and the percentage of free leptin were measured in cord plasma and plasma at 3 days of age of 13 term infants of mothers with gestational diabetes mellitus (GDM) and 13 term infants of healthy mothers. Gestational age was 40.2 (1.4) weeks, and birth weight was 3693 (549) g (means (SD)). RESULTS: At birth, infants of mothers with GDM had significantly higher concentrations of total, bound, and free leptin and a higher percentage of free leptin (all p < 0.05). In all infants, these concentrations were significantly lower at 3 days of age than at birth (all p < 0.003), and the differences in concentrations of total, bound, and free leptin between the two groups were no longer significant. In infants of mothers with GDM, the percentage of free leptin remained unchanged, and was higher (p<0.05) than in infants of healthy mothers; in the latter group the percentage of free leptin significantly declined (p = 0.02). CONCLUSIONS: GDM appears to influence fetoplacental leptin metabolism. This effect may be mediated through altered maternal glucose metabolism, or insulinaemia, or both.     

母亲妊娠期糖尿病对新生儿左心功能的影响

目的：评估妊娠期糖尿病（GDM）母亲的新生儿左心功能状况。方法：GDM母亲娩出的新生儿40例（GDM组）及正常新生儿40例（对照组）作为研究对象,应用超声二维斑点追踪成像技术检测室间隔厚度、左室后壁厚度、射血分数,并计算左室旋转和扭转参数。结果：GDM组新生儿室间隔舒张厚度（0.45±0.06 mm）较对照组（0.34±0.05 mm）增大;GDM组左室后壁舒张厚度（0.45±0.17 mm）亦较对照组（0.31±0.02 mm）增大,差异均有统计学意义（P0.05）。GDM组新生儿内膜旋转峰值、外膜旋转峰值、平面旋转峰值、跨壁扭转峰值均较对照组升高,差异有统计学意义（P<0.05）。结论：GDM母亲的新生儿左心室的形态和旋转及扭转运动发生变化,心功能虽受到损害,但处于代偿状态,能维持正常的射血功能。超声二维斑点追踪成像技术可作为早期检测新生儿左心功能的良好手段。     

Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age

Background: It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non‐exposed offspring. Subjects: Offspring of T1DM (n = 16), GDM (n = 22) and mothers without diabetes (n = 25) born at Oulu University Hospital. Aim: To assess insulin secretion and insulin resistance in the offspring of T1DM and GDM at preschool age in comparison with offspring of non‐diabetic mothers. Methods: Anthropometric measurements and intravenous glucose tolerance testing were performed. First‐phase insulin response (FPIR) and homoeostasis model assessment (HOMA) values were calculated. Pregnancy and birth data were analysed in relation to later metabolic parameters in all three groups using one‐way analysis of variance (anova ) and analysis of covariance (ancova ). Results: At a mean age of 4.9 yr, offspring of T1DM had increased fasting serum insulin concentrations (p = 0.044), FPIR (p = 0.034) and HOMA‐B values (p = 0.008) compared with offspring of GDM or with offspring of healthy controls (statistically non‐significant). The GDM gained least weight during pregnancy, and when adjusted for maternal weight gain during pregnancy, there were no statistically significant differences between study groups. Conclusions: Prenatal exposures to maternal type 1 and gestational diabetes may have different effects on postnatal glucose metabolism in the offspring assessed at a mean age close to 5 yr. Maternal weight gain in pregnancy may affect the postnatal glucose metabolism in the offspring.