The changes in the humoral immune system during pregnancy with diabetes

Gestational diabetes (GDM) is a carbohydrate intolerance of different severity with the onset during the pregnancy. GDM is a complication observed in 1-3% of pregnancies and has an important negative influence on foetal development. However most women with GDM do develop diabetes type 2, gestational diabetes could also be the beginning of a slow-progress towards the clinical onset of diabetes type 1. It is now possible, on the basis of the presence of antibodies directed against pancreatic autoantigens (ICA, GADA, IA-2A, IAA) to detect in the early stage of the autoimmune process leading to development of insulin-dependent diabetes (IDDM). In the present review we have summarised actual studies concerning the immune humoral alterations directed against pancreatic B cells in pregnant women with diabetes. We have also discussed the potential clinical implications of the presence of pancreatic autoantibodies in pregnant women with diabetes for the future risk of IDDM.     

Nutritional intake and placental size in gestational diabetic pregnancies--a preliminary observation

A disproportionately large placenta may represent an adaptive response to adverse intrauterine conditions. Both maternal nutritional intake and presence of gestational diabetes (GDM) have been found to affect relative placental growth. As dietary modification is part of the standard management in GDM women, the observed increase in placental size in these women may be partly due to dietary modification. In this study, we set out to examine the relationship between dietary intake and placental size in GDM pregnancies. Food diaries for five consecutive days for 52 women diagnosed with GDM were obtained to assess their nutritional intake in terms of total calories, carbohydrate, protein and fat. Spearman's correlations were calculated for nutritional intake and various factors that may correlate with placental weight. There was a significant inverse relationship (P=0.021) between placental weight and protein intake. No correlations with the other two nutritional components could be demonstrated. Maternal nutritional intake was not correlated with infant birthweight. It is possible that dietary modulations improve GDM pregnancy outcome, not only by improving glycaemic controls but also by affecting placental growth by altering the proportion of protein intake.     

Could serum levels of irisin be used in gestational diabetes predicting?

ObjectiveGestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy leading to acute and chronic complications in both mother and newborn. The pathogenesis of GDM has not been fully understood, However, since the disease shares risk factors with type 2 diabetes mellitus (T2DM), a relationship between these two disease states is plausible. The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate the relationship between irisin levels and gestational diabetes mellitus and the possible benefits of the metabolic profile.Materials and methodsWe performed a cross-sectional analysis of circulating levels of irisin in 100 pregnant women similar for age and body mass index and the groups included 50 gestational diabetic patients and 50 healthy pregnant volunteers. Serum irisin levels were measured by ELISA kit.ResultsMean age and body mass index levels were similar in both groups. Median HbA1c, fasting blood glucose, Glucose 1 h, Glucose 2 h and fasting insülin levels were higher in with gestational diabetic patients compared to the control group. In gestational diabetic group, the median irisin level was lower than in the control group.ConclusionSerum irisin levels were lower in gestational diabetic patients. Further investigations are needed to explore the underlying biological effects of irisin on pregnant women.     

Adiponectin SNP45TG is associated with gestational diabetes mellitus

Introduction  

Diabetes and pregnancy can be associated in two ways: pregnancy that occurs in women who are already diabetic (diabetes of pre-gestational origin); and diabetes that occur in women who are already pregnant [gestational diabetes mellitus (GDM) (O’sullivan 1961)]. Patients with previous GDM history have higher risk of developing diabetes outside of pregnancy. Accumulating literature had suggested that adiponectin plays a role in the pathophysiology of this metabolic syndrome, and several of the common single nucleotide polymorphisms (SNP) in adiponectin gene have been identified in type 2 diabetes. Thus, one of the commonly found SNP was studied to determine its association with GDM.     

Physiopathology and nutritional care of patients with gestational diabetes

Maternal risks include the development of diabetes after pregnancy, as well as having an infant with macrosomia, with elevated risk of developing obesity and diabetes in childhood. The main goal of treatment is to maintain an adequate glycemic control during pregnancy and guarantee the recommended weight gain. The first treatment strategy is diet therapy, however, some women need insulin therapy to achieve adequate glycemic control. The risk of diabetic fetopathy decreases when maintaining postprandial glycemic levels within normal ranges. These levels are directly associated with the amount and type of carbohydrates consumed during meals. So, nutrition therapy should be an integral part of gestational diabetes treatment. Nutrition therapy includes a complete nutrition assessment, an individual food plan that meets energy and protein requirements for pregnancy (in obese women never lesser than 1,700 kcal/day), in which lipids and carbohydrates may provide lesser than 40 and between 40 and 45% of total energy intake. Education about food groups that provide carbohydrates, portion sizes and how to achieve an equal carbohydrate distribution throughout the day should be provided. Orientation about eating healthy fats and increasing the consumption of high-fiber foods should also be included. This approach requires that treatment of women with gestational diabetes should be provided by a multidisciplinary team, including nutrition specialists.     

Type 1 diabetes and pregnancy

Type 1 diabetes in pregnancy presents multiple challenges to healthcare groups. Although there are debates regarding the precise pathophysiology of the different complications of type 1 diabetes during pregnancy, there is increasing evidence that good periconception and early pregnancy glycaemic control will reduce the rate of all complications, including macrosomia. The provision of organized prepregnancy care for this group allows an opportunity to reinforce the need for tight glycaemic control, to commence vitamin supplementation, to identify those with complications of diabetes who require more specialist evaluation and preparation, and to inform women of pregnancy risks. How this type of detailed care is provided is a major organizational issue for all healthcare systems. Optimal outcome during pregnancy is achieved by intense management by both obstetric and diabetic services. Many interventions and strategies during pregnancy, including the degree of glycaemic control, have a poor evidence base. The demands on pregnant women with type 1 diabetes should not be underestimated.     

Pregnancy resolutions among pregnant teens: termination,parenting or adoption?

Women with gestational diabetes mellitus (GDM) and their offsprings are at increased risk of future type 2 diabetes and metabolic abnormalities. Early diagnosis and proper management of GDM, as well as, postpartum follow-up and preventive care is expected to reduce this risk. However, no large scale prospective studies have been done particularly from the developing world on this aspect. The objective of this study is to identify and follow a cohort of pregnant women with and without GDM and their offspring to identify determinants and risk factors for GDM, for various pregnancy outcomes, as well as, for the development of future diabetes and metabolic abnormalities. This is a prospective cohort study involving pregnant women attending prenatal clinics from urban, semi-urban and rural areas in the greater Chennai region in South India. Around 9850 pregnant women will be screened for GDM. Socio-economic status, demographic data, obstetric history, delivery and birth outcomes, perinatal and postnatal complications, neonatal morbidity, maternal postpartum and offsprings follow-up data will be collected. Those diagnosed with GDM will initially be advised routine care. Those unable to reach glycaemic control with diet alone will be advised to take insulin. Postpartum screening for glucose abnormalities will be performed at months 3 and 6 and then every year for 10 years. The offsprings will be followed up every year for anthropometric measurements and growth velocity, as well as, plasma glucose, insulin and lipid profile. In addition, qualitative research will be carried out to identify barriers and facilitators for early GDM screening, treatment compliance and postpartum follow-up and testing, as well as, for continued adherence to lifestyle modifications. The study will demonstrate whether measures to improve diagnosis and care of GDM mothers followed by preventive postpartum care are possible in the routine care setting. It will also map out the barriers and facilitators for such initiatives and provide new evidence on the determinants and risk factors for both GDM development and occurrence of adverse pregnancy outcomes and development of future diabetes and metabolic abnormalities in the GDM mother and her offspring.     

妊娠期糖尿病孕妇体重指数变化与围产结局的关系

目的探讨妊娠期糖尿病(GDM)孕妇妊娠前体重指数(BMI)及妊娠期体重指数增幅与围产结局的关系。方法2006年1月至2007年12月间在浙江大学医学院附属妇产科医院产科门诊行常规检查并确诊为GDM的238例患者,按妊娠前体重指数分为正常组(18.5≤BMI<23)、超重组(23≤BMI<25)、肥胖组(BMI≥25),按早孕至终止妊娠前BMI的总增幅,分为A组(BMI总增幅<4),B组(4≤BMI总增幅≤6),C组(BMI总增幅>6),比较分析各组间围产结局的差异。结果肥胖组子痫前期、早产发生率均(26.0%,32.7%)显著高于正常组(11.9%,8.3%)及超重组(10.8%,13.7%),差异均有统计学意义(P<0.05)。正常组孕妇胎儿窘迫发生率(8.3%)显著低于超重组(23.5%)和肥胖组(23.1%),差异有统计学意义(P<0.05)。B组子痫前期(10.4%)、羊水过多(10.4%)、胎膜早破(10.4%)、胎儿窘迫(11.3%)和早产(8.0%)的发生率均明显低于C组(22.2%,23.8%,25.3%,30.2%,30.2%),差异均有统计学意义(P均<0.05)。C组胎膜早破发生率明显高...     

Gestational diabetes exhibits lack of carnitine deficiency despite relatively low carnitine levels and alterations in ketogenesis.

OBJECTIVE: Previous studies have underlined the importance of the carnitine shuttle system and its dysfunction both in normal pregnancy and in type 1 and 2 diabetes. The objective of this paper was to delineate more systematically the role of the carnitine shuttle system in normal pregnancy and in gestational diabetes. METHODS: A total of 119 women matched for age comprised three groups: 40 normal adult non-pregnant women (NNP), 46 normal pregnant women with uncomplicated pregnancy (NP) and 33 women with gestational diabetes (GDM). The latter group was further subdivided into those being managed either by diet alone (25 women, GDM-D) or by insulin (8 women,GDM-I). The following biochemical parameters were assayed: fasting plasma total, free and acyl-carnitine, FFA and beta-OH-butyrate, together with several essential anthropometric parameters. RESULTS: Women with GDM, in contrast to the control groups, displayed the biochemical features characteristic of insulin resistance: higher body weight, higher BMI, higher skinfold and higher HbAlc levels. No differences on any parameters were found between the two GDM subgroups. Both NP and GDM groups had low levels of total carnitine compared to NNP control group, but surprisingly, the GDM group did not exhibit any further decrease of carnitine levels, as would have been expected by the combination of pregnancy and diabetes. Both groups, despite these low carnitine levels, had no clinical symptoms of carnitine deficiency. Furthermore, the GDM group displayed higher levels of FFA and beta-hydroxybutyrate, which were statistically significant compared to the other two control groups. CONCLUSIONS: The data corroborate the negative effect of normal gestation on the carnitine shuttle system, while they document for the first time that GDM does not further affect the efficiency of the carnitine system. The mild effect of GDMon carnitine status could be explained by the concurrent increased gluconeogenesis, a process which does not affect directly carnitine metabolism.     

Perinatal complications in women with gestational diabetes mellitus

BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non-diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus. METHODS: Included were 327 women with gestational diabetes mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose tolerance test because of risk factors for gestational diabetes. Women with gestational diabetes mellitus were treated with low-caloric diet and insulin when appropriate, while women in the control group received routine antenatal care. RESULTS: Gestational age at delivery was significantly lower in the group with gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7 weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of macrosomia was increased, although not statistically significant (8% vs. 2%, p=0.07), and the rate of admission to the neonatal ward was significantly increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with early diagnosis of gestational diabetes mellitus had a significantly increased need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a significantly higher occurrence of diabetes mellitus at follow-up from two months until three years postpartum. CONCLUSIONS: This study of women with gestational diabetes mellitus and non-diabetic pregnant women showed that gestational diabetes mellitus was associated with a significantly lower gestational age at delivery and an increased rate of admission to the neonatal ward. Women diagnosed with GDM before 20 weeks of gestation had an increased need for insulin treatment during pregnancy and a high risk of subsequent overt DM, compared with women diagnosed with GDM later in pregnancy.     

妊娠合并自身免疫性1型糖尿病对母胎的影响及诊治

妊娠合并自身免疫性1型糖尿病是孕期常见的合并症之一,可导致母儿并发症增加。文章介绍了妊娠合并自身免疫性1型糖尿病的筛查和诊断标准,提出做好充足的孕前准备,加强孕期监护,应用饮食控制以及胰岛素注射使血糖降至理想状态可降低母儿并发症,改善妊娠结局。     

妊娠期糖代谢异常相关因素的研究

目的 探讨妊娠期糖尿病（GDM）及妊娠期糖耐量低减（GIGT）发病的高危因素。方法 采用前瞻性对照研究的方法,对2004年2月至8月,在北京大学第一医院妇产科门诊行产前检查诊断的糖代谢异常孕妇[其中GDM85例（GDM组）、GIGT63例（GIGT组）]和125例糖代谢正常孕妇（对照组）的临床资料进行单因素及多因素logistic回归分析,探讨各因素对GDM和GIGT发病的影响。结果 （1）GDM组及GIGT组孕妇平均年龄、孕前体重指数、确诊前孕妇平均每周体重增长均明显高于对照组（P〈0．05）。（2）GDM组及GIGT组孕妇每日主食及水果摄人量也明显高于对照组（P〈0．05）,而且GDM组与GIGT组比较,差异有统计学意义（P〈0．05）。（3）GDM组、GIGT组及对照组糖尿病遗传家族史发生率分别为42．4％、36．5％及19．2％;孕前月经不调发生率分别为16．5％、23．8％及6．4％;多囊卵巢综合征（PCOS）发生率分别为5．9％、3．2％及0;妊娠期外阴阴道念珠菌病（VVC）发生率分别为15．3％、17．4％及7．2％。GDM组及GIGT组以上各指标与对照组比较,差异均有统计学意义（P〈0．05）。（4）多因素logistic回归分析显示,孕妇年龄、月经不调、孕前体重指数、确诊前孕妇平均体重增加、自然流产史、VVC均为妊娠期糖代谢异常的高危因素。结论 孕妇年龄、月经不调、自然流产史、孕前肥胖、孕期体重增加过快、VVC,为GDM和GIGT发病的独立高危因素。PCOS、糖尿病家族遗传史对GDM发病有一定影响,但不是独立高危因素。     

Pre-existing type I and type II diabetes in pregnancy

Diabetes mellitus is a long term chronic condition. The prevalence of diabetes in pregnancy is 2–5% in the UK of both gestational diabetes and pre-existing diabetes. The pregnancy outcomes for pre-existing type I and type II diabetic women are worse than for non-diabetic mothers. There is a higher incidence of stillbirth, macrosomia and congenital malformations. Pre-pregnancy counselling is essential to prepare for pregnancy, to tighten glycaemic control and review medication prior to pregnancy. Multi-disciplinary care is required throughout the antenatal period, to optimise blood glucose monitoring and control. Screening for diabetic complications such as nephropathy and retinopathy is necessary at every trimester to detect progression of disease. The timing, mode and management of delivery with a plan to maintain glycaemic control during this time should be discussed by 36 weeks. After completion of 38 weeks' gestation, induction of labour may be considered. This review will discuss the management of pre-existing type I and type II diabetic women from the preconception period to the postpartum period.     

Determinants of Birth-weight in Women with Established and Gestational Diabetes

Summary: Increased birth-weight (macrosomia) can complicate the diabetic pregnancy, but many factors other than hyperglycaemia can influence birth-weight, in particular maternal obesity. In a mixed population (European, Maori and Pacific Islander) with a high prevalence of glucose intolerance and obesity we have examined the relative impact of various maternal factors on birth-weight in women with both established and gestational diabetes. Mean birth-weight was significantly greater in women with established or gestational diabetes than in controls (p < 0.0001), but was similar in women with gestational and established diabetes, despite glycaemic control being significantly poorer (p < 0.0001) in the latter. Birth-weight closely paralleled prepregnancy body mass index rather than glycaemic control, but in Maori women it was lower than expected, probably because of their high prevalence of smoking. Daily cigarette consumption was negatively correlated with birth-weight (p<0.01) despite the smokers having significantly poorer glycaemic control (p<0.001). The most significant variables influencing birth-weight in the diabetic pregnancy were gestational age at delivery, prepregnancy body mass index, maternal height, estimated weight gain during pregnancy, the presence of hypertension and cigarette smoking (the latter 2 having negative effects on birth-weight). Glycaemic control in the last half of pregnancy was not significant in this analysis. We conclude that within the limits of glycaemic control which we obtained, birth-weight was largely determined by maternal factors other than hyperglycaemia. Birth-weight thus has severe limitations as an outcome measure of the diabetic pregnancy.     

Diabetic pregnancy outcomes in mothers treated with basal insulin lispro protamine suspension or NPH insulin: a multicenter retrospective Italian study

Objective: The aim of this study was to study the efficacy and safety of long-acting insulin analog insulin lispro protamine suspension (ILPS) in diabetic pregnant women.

Methods: In a multicenter observational retrospective study, we evaluated pregnancy outcome in 119 women affected by type 1 diabetes and 814 with gestational diabetes (GDM) treated during pregnancy with ILPS, compared with a control group treated with neutral protamine hagedorn (NPH) insulin.

Results: Among type 1 diabetic patients, fasting blood glucose at the end of pregnancy was significantly lower in ILPS-treated than in NPH-treated patients. HbA1c levels across pregnancy did not differ between groups. Caesarean section and preterm delivery rates were significantly lower in the ILPS-women. Fetal outcomes were similar in the ILPS and NPH groups. Among GDM women, fasting blood glucose at the end of pregnancy was significantly lower in ILPS-treated than in NPH-treated patients. Duration of gestation was significantly longer, caesarian section and preterm delivery rates were lower in the ILPS-treated group. In addition, there were significantly fewer babies with an excessive ponderal index or neonatal hypoglycemic episodes in the ILPS group than in the NPH group.

Conclusions: Association of ILPS with rapid-acting analogs in pregnancy is safe in terms of maternal and fetal outcomes.     

妊娠糖尿病对母婴影响的分析

目的：研究早期诊断妊娠糖尿病（ＧＤＭ）控制血糖，以减少母婴并发症。方法：观察和分析妊娠糖尿病２２例及健康孕妇３０例的妊娠结局。结果：ＧＤＭ组中病理妊娠的发生率占５４５４％，手术产率占７２７２％，胎婴儿疾病的发生率为６８１７％；对照组病理妊娠的发生率占２２７２％，手术产率占３１７２％，胎婴儿疾病的发生率为１８１８％。ＧＤＭ组母婴合并症的发生率明显高于正常孕妇，并与血糖水平密切相关。结论：早期诊断ＧＤＭ及控制血糖是减少妇婴并发症的关键。     

Stillbirth in diabetic pregnancies

Pregnancy in women with pregestational diabetes is associated with high perinatal morbidity and mortality. Stillbirth accounts for the majority of cases with perinatal death. Intrauterine growth restriction, pre-eclampsia, foetal hypoxia and congenital malformations may be contributing factors, but more than 50% of stillbirths are unexplained. Majority of stillbirths are characterised by suboptimal glycaemic control during pregnancy. Foetal hypoxia and cardiac dysfunction secondary to poor glycaemic control are probably the most important pathogenic factors in stillbirths among pregnant diabetic women. There is thus a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy. Antenatal surveillance tests including ultrasound examinations of the foetal growth rate, kick counting and non-stress testing of foetal cardiac function are widely used. However, future research should establish better antenatal surveillance tests to identify the infants susceptible to stillbirth before it happens.     

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

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

Coffee consumption and the risk of gestational diabetes mellitus

BACKGROUND: Coffee consumption has been associated with a decreased risk of type 2 diabetes mellitus. We examined the relationship between coffee consumption and the risk of gestational diabetes mellitus [GDM]. METHODS: In this prospective study, 1744 non-diabetic pregnant women were questioned during early gestation about their coffee consumption. We studied the association of coffee consumption before and during pregnancy, and the subsequent risk of GDM. Generalised, linear models were fitted to estimate risk ratios and 95% confidence intervals. RESULTS: Women who reported moderate pre-pregnancy caffeinated coffee intake had a significantly reduced risk of GDM (adjusted RR 0.50; 95% CI 0.29-0.85) compared with non-consumers. No risk reduction was associated with decaffeinated coffee intake. CONCLUSIONS: Moderate pre-pregnancy caffeinated coffee consumption may have a protective association with GDM. Prospective studies, including a wider range of consumption habits, are necessary.     

Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins

Our aims were: 1. To investigate if women with PCOS who become pregnant using gonadotrophins have a higher incidence of gestational diabetes mellitus (GDM) compared to spontaneously pregnant matched control women, 2. To compare the prevalence of GDM in PCOS women with that in women with hypo/eugonadotrophic hypogonadism and in unexplained infertility and 3. To investigate differences in pregnancy outcomes between the groups. This was a retrospective case-control study. Women with PCOS were matched with a control by age, BMI, and ethnicity. There were 60 women with PCOS, 11 with hypogonadotrophic hypogonadism, 6 with eugonadotrophic hypogonadism, and 12 with unexplained infertility. Control women were those who attended a major public hospital for antenatal care and delivery We found no difference in the prevalence of GDM between the PCOS (22%) and the controls (17%) or between the PCOS and other groups. Women with GDM (diet or insulin controlled) had a significantly higher BMI than women without GDM (p = 0.019). There was no difference in pregnancy outcomes between the groups. There was a significant dependence of babies' birthweight on mother's BMI (p<0.001).