Diabetic patient and reproduction

Current views and opinions on pregnancy in diabetic mothers are presented. Special attention is paid to carbohydrate metabolism, pregestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM) and unclear heterogenous etiology of gestational diabetes mellitus (GDM). Suggestions for identification, diagnosis and treatment of GDM with an emphasis on early screening strategy are given. Obstetrical management and possible perinatal complications are discussed.     

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］     

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.     

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.     

Leptin and metabolic hormones in infants of diabetic mothers

AIMS: To investigate the effect of maternal diabetes on leptin in term newborns and to determine whether leptin correlates with insulin and its associated biochemical parameters in support of the hypothesis that a functional "adipoinsular axis" might exist at this stage of development. METHODS: A total of 116 term newborns were prospectively enrolled and categorised into three groups: 44 were infants of non-diabetic mothers (control group C); 41 were infants born to mothers with gestational diabetes on dietary treatment (group D); and 31 were infants born to mothers with gestational or pregestational diabetes on insulin treatment (group I). RESULTS: No significant difference in serum leptin was observed between the three groups; the results of the study population were therefore pooled and analysed. Serum leptin correlated significantly with serum insulin, insulin:glucose ratio, birth weight, body length, body mass index, placenta weight, and maternal HbA(1c). Female infants had significantly higher serum leptin than male infants. All parameters except placenta weight and body length remained significantly associated with serum leptin when multivariate stepwise regression analysis was applied. Subgroup analysis revealed a significant correlation between serum leptin and cortisol in group D. CONCLUSIONS: There was no significant difference in serum leptin between infants born to diabetic and non-diabetic mothers, though infants born to mothers requiring insulin treatment had the highest median serum leptin concentrations. The significant association between serum leptin and insulin or insulin:glucose ratio supports the hypothesis that a functional adipoinsular axis might exist in term newborns. Furthermore, the significant correlation between maternal HbA(1c) and circulating leptin of the studied infants suggests that the clinical control of maternal diabetes could affect the regulation of serum leptin in these infants.     

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...     

Erythrocyte indicators of oxidative stress in gestational diabetes

Foetuses born to mothers with gestational diabetes are at increased risk of developing respiratory distress, foetal macrosomia, foetal anomalies and platelet hyperaggregability. High blood glucose level induces oxidative stress and decreases antioxidant defences. The present study discusses the possibility of lipid peroxidation and protein oxidation in both maternal and foetal erythrocytes as an indicator of oxygen radical activity. The level of lipid peroxidation and protein oxidation in erythrocytes was estimated in 20 mothers with gestational diabetes and their newborns. The maternal age varied between 19 and 42 y and foetal age ranged between 34 and 39 weeks. The proteolytic activities in the erythrocyte lysates obtained from mothers with gestational diabetes and their newborns were significantly greater [(mean ± SD) 24.41 ± 9.05 and 16.70 ± 3.36μM of amino groups/g haemoglobin, n = 20, respectively] than those from control group (10.18 ± 4.84 and 14.64 ± 6.21 μM amino groups/g haemoglobin, n = 15, respectively; p < 0:05 in both cases). Similarly erythrocyte malondialdehyde levels were significantly elevated in babies born to mothers with gestational diabetes (10.11 ±2.21 nM/g haemoglobin) when compared to controls (6.8 ± 3.75 nM/g haemoglobin) (p < 0:05). In the erythrocytes of mothers with gestational diabetes, malondialdehyde levels correlated significantly with glycated haemoglobin levels (p < 0:01). The results of this study indicate that the oxidative stress induced by gestational diabetes manifests as increased lipid peroxidation and protein oxidative damage in the erythrocytes of both mothers with gestational diabetes and their newborn infants.     

Macrosomia,top of the iceberg: The charm of underlying factors

Background: Macrosomia is associated with childhood obesity. Gestational diabetes mellitus (GDM) is a risk factor for macrosomia. The aim of this large‐scale investigation was to determine the incidence, risk factors, characteristic features, and perinatal outcome of macrosomic infants. Methods: This prospective study was carried out on 6385 newborns. Demographic data included maternal age, paternal age, type of delivery, sex, parity and gestational age at delivery. Anthropometric measurements were recorded. ABO/Rh typing was performed and GDM was diagnosed. Results: Out of 6385 term deliveries, 477 infants (7.47%) were macrosomic. Incidence of GDM was 0.6% and 4.8% in the control group and in macrosomic births, respectively. Incidence of GDM(+) cases was 4% among macrosomic infants weighing 4000–4500 g. GDM(+) cases were densely populated (11%) in macrosomic infants weighing ≥ 4500 g (P≤ 0.05). Male/female ratio was significantly higher in macrosomic infants weighing ≥ 4500 g than those weighing 4000–4500 g (P≤ 0.05). High parental age was the risk factor for GDM. Blood group A was the most frequently observed type among mothers with macrosomic infants, however, blood group O was dominant in cases with GDM. In multivariate logistic regression analysis, the male infant was the most striking infant characteristic and GDM was the most striking maternal characteristic that were significantly associated with increased odds of macrosomic birth. Conclusions: This research reports the association between blood group system and macrosomia as well as parental age and GDM simultaneously. Our study reports a prevalence of GDM in both infants with normal birth weight and macrosomic newborns at the same time.     

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。     

Level of maternal triglycerides is a predictor of fetal macrosomia in non-obese pregnant women with gestational diabetes mellitus

Background

The role of maternal serum triglycerides (TGs) in the development of fetal macrosomia in different subgroups of body mass index (BMI) has received little attention. The aim of this study was to determine the association between the level of maternal TGs and fetal macrosomia in Iranian pregnant women of different BMI subgroups with gestational diabetes mellitus (GDM).

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.     

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.     

Plasma protein Z levels in healthy and high-risk newborn infants

AIM: To evaluate plasma protein Z (PZ) levels in healthy and high-risk newborn infants. METHODS: A longitudinal observational study was conducted. Inclusion criteria were: healthy term and preterm newborns normal for gestational age and newborns belonging to one of the following groups: newborns small for gestational age (SGA), newborns affected by respiratory distress syndrome (RDS), newborns from mothers with pre-eclampsia. Newborns with sepsis, congenital malformation or haemorrhagic disorders were excluded. Plasma PZ levels, protein C (PC) concentration, PC activity and protein-induced vitamin K absence levels were measured. RESULTS: 53 newborns were enrolled into the study. PZ and PC antigen levels varied significantly among analysed subgroups on day 1 (p < 0.01): lower levels of these inhibitors were found in RDS newborns (group C), newborns from mothers affected by pre-eclampsia (group D) and SGA newborns (group E) than in healthy term and preterm newborns (groups A and B). CONCLUSION: PZ deficiency occurs in newborns affected by severe RDS, in newborns from pre-eclamptic mothers and in SGA newborns, probably owing to activated coagulation in the first two conditions and to reduced PZ synthesis in the last condition.     

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.     

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.     

测定脐血脑钠肽对血糖异常孕妇的胎儿心功能评价

目的：探讨脐血脑钠肽（BNP）评价血糖异常孕妇胎儿心功能的可行性及高血糖对胎儿心功能的影响。方法：妊娠期血糖异常孕妇24例,包括妊娠期糖尿病18例和糖耐量受损6例,按分娩前血糖值的高低分为控制欠佳组（7例）和控制较好组（17例）,孕末期行胎儿超声心动图测量心脏相关指标;正常妊娠孕妇25例为对照组。于胎儿分娩时留脐血,测定BNP浓度。结果：血糖异常组胎儿脐血BNP值明显高于对照组,分别为（114.0±39.0）和（80.6±13.7） pg/mL（P<0.01）,其中血糖控制欠佳组高于控制较好组（142.1±44.1 pg/mL vs 102.4±31.2 pg/mL;P<0.01）。脐血BNP在妊娠期糖尿病和糖耐量受损两组间差异无显著性,与孕末期胎儿左室壁厚度呈正相关,与二尖瓣A峰、E/A比值分别呈正、负相关（r值分别为0.715,0.491和-0.507,P<0.05）。结论：妊娠期高血糖时脐血BNP水平明显升高,与孕妇血糖控制情况及胎儿心功能变化相关联,可反映胎儿心功能的潜在损害。良好血糖控制可能减轻这一影响。［中国当代儿科杂志,2009,11（10）：805-808］     

Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes

Diabetes during pregnancy may be associated with a high rate of congenital anomalies, disturbances of intrauterine growth and often post-natal neurobehavioral abnormalities in the offspring. The latter are associated with pregestational (PGD) as well as with gestational diabetes (GD). In this review we discuss the effects of maternal glucose intolerance on the long-term growth and development of the offspring. In well-controlled diabetes, birth weight is often within normal limits while in partially controlled diabetes newborns are often macrosomic. In PGD mothers with nephropathy, newborns tend to be born prematurely and small for gestational age (SGA). Offspring of diabetic mothers are often large and overweight in comparison to controls. Their long-term development is sometimes impaired. Delayed brain maturity is often observed in newborns of diabetic mothers compared to controls. The IQ scores of the children born to well controlled diabetic mothers are generally similar to that of control children. However, these children perform less well than controls in fine and gross motor functions. They also seem to have a higher rate of inattention and/or hyperactivity as observed by various tests and questionnaires. In our studies we found, in accordance with published literature, a negative correlation between the performance of the children born to mothers with PGD or GD on various neurodevelopmental and behavioral tests and the severity of maternal hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. In conclusion: PGD or GD may adversely affect intrauterine and postnatal growth, attention span and motor functions of the offspring, but not their cognitive ability unless complicated by nephropathy or hypertension. These effects are negatively correlated with the degree of maternal glycemic control.     

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.     

Congenital abnormalities in the offspring of pregnant women with type 1, type 2 and gestational diabetes mellitus: A population‐based case‐control study

To estimate the risk of structural birth defects (i.e. congenital abnormalities [CA]) in the offspring of pregnant women with type 1 (DM‐1), type 2 (DM‐2) and gestational diabetes mellitus (GDM) and to check the efficacy of recent specific care of diabetic pregnant women in the reduction of DM‐related CA. Comparison was made of the occurrence of medically recorded types of diabetes mellitus in pregnant women who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996. In the case group, which included 22 843 offspring, there were 79 (0.35%) pregnant women with DM‐1, 77 (0.34%) pregnant women with DM‐2 and 120 (0.53%) pregnant women with GDM. The control group comprised 38 151 newborns, and 88 (0.23%), 141 (0.37%) and 229 (0.60%) pregnant women with DM‐1, DM‐2 and GDM, respectively. The total rate of cases with CA was higher only in the DM‐1 group (adjusted OR with 95% CI: 1.5, 1.1–2.0) and within four specific types/groups: isolated renal a/dysgenesis, obstructive CA of the urinary tract, cardiovascular CA and multiple CA; namely, caudal dysplasia sequence. The risk of total CA was lower in the present study compared to the risk in previous studies and the DM‐1‐related spectrum of CA was also different. There was no higher risk of total CA in the offspring of pregnant women with DM‐2 and GDM. The certain part of maternal teratogenic effect of DM‐1 is preventable with appropriate periconceptional and prenatal care of diabetic women.