Abnormal Development - Maternal Diabetes

Embryology - 11 Dec 2023        Expand to Translate
Google Translate - select your language from the list shown below (this will open a new external page)
العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.

Introduction

World Diabetes Day 17 Gestational Diabetes

Human Pancreatic Islets (Islets of Langerhans)

Diabetes during pregnancy, maternal diabetes in any form, whether pregestational (type 1 or type 2) or gestational diabetes, increases the risk for adverse maternal and infant outcomes and impacts developmentally on the same systems. In the USA for the year 2000 the most frequently reported medical risk factors were: pregnancy-associated hypertension (38.8 per 1,000 live births) and diabetes (29.3) follwed by anemia (23.9).

A tenfold increase in the prevalence of hypertension and a 10 percent incidence of gestational diabetes have been reported in obese pregnant women. Women who have had gestational diabetes are much more likely to develop type 2 diabetes.

Note that in some countries reporting on diabetes on birth certificates has a field that indicates whether the "mother had diabetes during pregnancy", but does not necessarily whether this was gestational or a pre-existing diabetes.

An estimated 917,000 (5.4%) Australian adults aged 18 years and over had diabetes in 2011–12, based on self-reported and measured data, from the ABS 2011–12 Australian Health Survey (Diabetes indicators, Australia 2016).

Links: endocrine pancreas | macrosomia | Prenatal Diagnosis | Neonatal Diagnosis

Some Recent Findings

Australia 2018 - new insulin users

Australia 2017 - new female insulin users

Australia - insulin-treated diabetes by type 2015

ultrasound assessment of maternal adipose tissue during first trimester screening for aneuploidies and risk of developing gestational diabetes "The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) ≥92 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG <92 mg/dL underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. ...Sonographic thickness of maternal visceral adipose tissue was greater in women with GDM than in non-diabetic patients, independently of other known risk factors associated with GDM in the 1st and in the 2nd trimester of pregnancy. Thus, this measurement may be considered of clinical use in 1st trimester screening." Incidence of insulin-treated diabetes in Australia (AIHW Web report 0 25 Mar 2020) In 2018, about 31,300 people began using insulin to treat their diabetes in Australia, of these 10,800 (34%) females began using insulin to treat gestational diabetes. Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring "Gestational diabetes mellitus (GDM) is an important factor involved in the pathogenesis of organ development in the offspring. Here, we analyzed the effects of GDM on odontoblastic differentiation of dental papilla cells (DPCs) and dentin formation in offspring and investigated their underlying mechanisms. A GDM rat model was induced by intraperitoneal injection of streptozotocin and offspring were collected. The results showed that GDM significantly affected odontoblast differentiation and dentin formation in offspring tooth. GDM activated the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-ĸB) signaling pathway and inhibited SMAD1/5/9 signaling to modulate the odontoblastic differentiation of DPCs in offspring. Inhibition of TLR4 signaling by treated with TAK-242 significantly reverses the suppression of odonto-differentiation of DPCs in diabetic offspring. Taken together, these data indicate GDM activated the offspring DPCs TLR4/NF-ĸB signaling, which suppressed the SMAD1/5/9 phosphorylation and then inhibited odontoblasts differentiation and dentin formation." tooth Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring "All 2 432 000 liveborn children without congenital heart disease in Denmark during 1977-2016. Follow-up began at birth and continued until first time diagnosis of CVD, death, emigration, or 31 December 2016, whichever came first. The primary outcome was early onset CVD (excluding congenital heart diseases) defined by hospital diagnosis. Associations between maternal diabetes and risks of early onset CVD in offspring were studied. Cox regression was used to assess whether a maternal history of CVD or maternal diabetic complications affected these associations. Adjustments were made for calendar year, sex, singleton status, maternal factors (parity, age, smoking, education, cohabitation, residence at childbirth, history of CVD before childbirth), and paternal history of CVD before childbirth. The cumulative incidence was averaged across all individuals, and factors were adjusted while treating deaths from causes other than CVD as competing events. Children of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood. If maternal diabetes does have a causal association with increased CVD rate in offspring, the prevention, screening, and treatment of diabetes in women of childbearing age could help to reduce the risk of CVD in the next generation." Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2 "Epidemiological studies show that maternal diabetes is associated with an increased risk of autism spectrum disorders (ASDs), although the detailed mechanisms remain unclear. The present study aims to investigate the potential effect of maternal diabetes on autism-like behavior in offspring. The results of in vitro study showed that transient hyperglycemia induces persistent reactive oxygen species (ROS) generation with suppressed superoxide dismutase 2 (SOD2) expression. Additionally, we found that SOD2 suppression is due to oxidative stress-mediated histone methylation and the subsequent dissociation of early growth response 1 (Egr1) on the SOD2 promoter. Furthermore, in vivo rat experiments showed that maternal diabetes induces SOD2 suppression in the amygdala, resulting in autism-like behavior in offspring. SOD2 overexpression restores, while SOD2 knockdown mimics, this effect, indicating that oxidative stress and SOD2 expression play important roles in maternal diabetes-induced autism-like behavior in offspring, while prenatal and postnatal treatment using antioxidants permeable to the blood-brain barrier partly ameliorated this effect. We conclude that maternal diabetes induces autism-like behavior through hyperglycemia-mediated persistent oxidative stress and SOD2 suppression. Here we report a potential mechanism for maternal diabetes-induced ASD." Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study "Indicators of childhood- and youth-onset diabetes may be useful for early detection of diabetes; there is a known association between composite exposure of parental type 2 diabetes and gestational diabetes mellitus with childhood- and youth-onset diabetes. We examined associations between gestational diabetes mellitus and incidence of childhood- and youth-onset diabetes in offspring. Using public health insurance administrative databases from Quebec, Canada, we randomly selected singleton live births with maternal gestational diabetes mellitus (1990-2007) and matched them 1:1 with singleton live births without gestational diabetes mellitus. Follow-up was to Mar. 31, 2012. We examined associations of diabetes in offspring with maternal gestational diabetes mellitus through unadjusted and adjusted Cox proportional hazards models. In secondary analyses, we separately considered age groups ranging from birth to age 12 years, and age 12 to 22 years. Gestational diabetes mellitus is associated with incident diabetes in offspring during childhood and adolescence. Future studies are needed to examine longer-term outcomes in patients with pediatric diabetes with a maternal history of gestational diabetes mellitus, to ascertain how they compare with other patients with childhood- or youth-onset diabetes, in terms of disease severity and outcomes." Report - Incidence of insulin-treated diabetes in Australia "In Australia 2017 there were 29,797 people who began using insulin to treat their diabetes, of these 9,053 (30%) women began using insulin to treat gestational diabetes." Review - Systemic endocrinopathies (thyroid conditions and diabetes): impact on postnatal life of the offspring "Fetal programming may influence childhood and adult life, determining the risk of specific diseases. During earlier stages of pregnancy, the transfer of maternal thyroid hormones to the fetus is vital for adequate neurologic development. The presence of severe maternal thyroid dysfunction, particularly severe iodine deficiency, is devastating, leading to irreversible neurologic sequelae. Moreover, mild maternal thyroid conditions, such as a mild-to-moderate iodine deficiency, may also lead to milder neurologic and behavioral conditions later during the life of the offspring. Maternal dysglycemia due to pregestational or gestational diabetes mellitus is another common situation in which fetal development encounters a hostile environment. Hyperglycemia in utero may trigger metabolic conditions in the offspring, including abnormalities of glucose tolerance and weight excess. Physicians assisting pregnant women have to be aware about these conditions, because they may go unnoticed if not properly screened. Because an early diagnosis and appropriate management may prevent most of the possible negative consequences for the progeny, the prevention, early diagnosis, and proper management of these endocrine conditions should be offered to all women undergoing pregnancy. Here, we comprehensively review the current evidence about the effects of maternal thyroid dysfunction and maternal dysglycemia on the cognitive function and carbohydrate metabolism in the offspring, two prevalent conditions of utmost importance for the child's health and development." PLoS Collection - Diabetes Prevention In this Collection, we feature PLOS articles that focus on the prevention of diabetes.

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Maternal Diabetes | gestational diabetes

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Comparative proteomic analysis of maternal peripheral plasma and umbilical venous plasma from normal and gestational diabetes mellitus pregnancies Gestational diabetes mellitus (GDM) increases many health risks in offspring. The study aims to investigate the underlying mechanism in fetal risk of GDM.We collected maternal peripheral plasma and umbilical venous plasma samples from 4 GDM and 4 control patients during their delivery at a university-based women's hospital. ...We identified 19 up-regulated proteins and 15 down-regulated proteins in GDM peripheral plasma, 29 up-regulated proteins and 69 down-regulated proteins in GDM umbilical venous plasma. Cholesteryl ester transfer protein (CETP) concentration was significantly lower in both GDM peripheral plasma and umbilical venous plasma. Upstream regulator analysis predicted follicle-stimulating hormone (FSH) as the activated regulator of differentially expressed proteins.The protein profiles in both GDM peripheral plasma and umbilical venous plasma between normal and GDM patients were significantly different. The results indicated that CETP and FSH might associates with health problem of GDM offspring." Maternal diabetes alters the development of ductus venosus shunting in the fetus "Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous (UV) distribution, including increased ductus venosus (DV) shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on UV and DV flow is not known. In pregnancies with pregestational diabetes mellitus, prioritized UV distribution to the fetal liver, and lower DV shunt capacity, both reduce the compensatory capability of the fetus and may represent an augmented risk during hypoxic challenges during late pregnancy and birth." ductus venosus Increased risk of cardiovascular disease in women with prior gestational diabetes "This study aims to investigate the effect of gestational diabetes mellitus (GDM) on the long-term risk of cardiovascular disease (CVD). PubMed and other databases were searched up to August 31, 2017. ... In the pooled analysis, women with previous GDM had a higher risk of CVD than those without (RR: 1.74, 95%CI: 1.28-2.35, I2=95.7%). Four studies reported the event of coronary artery disease (CAD) and two studies reported stroke. Women with prior GDM have increased risk of CVD." Neonatal outcomes of live-born term singletons in vertex presentation born to mothers with diabetes during pregnancy by mode of birth: a New South Wales population "To investigate the association between the mode of birth and adverse neonatal outcomes of macrosomia (birth weight ≥4000 g) and non-macrosomic (birth weight <4000 g) live-born term singletons in vertex presentation (TSV) born to mothers with diabetes (pre-existing and gestational diabetes mellitus (GDM)). ...Pregnant women with diabetes, particularly those with suspected fetal macrosomia, need to be aware of the increased likelihood of adverse neonatal outcomes following instrumental vaginal birth and intrapartum CS when planning mode of birth." Proportion of insulin-treated diabetes by type (2015) "The 2017 published AIHW fact sheet provides the latest available national data on new cases of insulin-treated diabetes in Australia. It shows that in 2015 there were 28,775 people who began using insulin to treat their diabetes in Australia: 63% had type 2 diabetes, 26% (18,142) had gestational diabetes, 9% had type 1 diabetes and 2% had other forms of diabetes or their diabetes status was unknown." Maternal diabetes causes developmental delay and death in early-somite mouse embryos "Maternal diabetes causes congenital malformations and delays embryonic growth in the offspring. We investigated effects of maternal diabetes on mouse embryos during gastrulation and early organogenesis (ED7.5-11.5). ...We conclude that failure of perigastrulation embryos of diabetic mothers to grow and survive is associated with their failure to shut down pathways that are strongly down-regulated in otherwise similar non-retarded embryos. Embryos that survive the early and generalized adverse effect of maternal diabetes, therefore, appear the subset in which malformations become manifest." mouse Prevalence of Gestational Diabetes Mellitus in Korea "The annual numbers of deliveries in 2009–2011 were 479,160 in 2009, 449,747 in 2010, and 377,374 in 2011. The prevalence of GDM during that period was 7.5% in 2009–2011: 5.7% in 2009, 7.8% in 2010, and 9.5% in 2011." Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy "During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. ... These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling." Nutrition | rabbit Prevalence Estimates of Gestational Diabetes Mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010 "Gestational diabetes mellitus (GDM) prevalence in 2010 was 4.6% as reported on the birth certificate, 8.7% as reported on the PRAMS questionnaire, and 9.2% as reported on either the birth certificate or questionnaire. The agreement between sources was 94.1% (percent positive agreement = 3.7%, percent negative agreement = 90.4%). There was no significant difference in GDM prevalence between 2007-2008 (8.1%) and 2009-2010 (8.5%, P = .15). Our results indicate that GDM prevalence is as high as 9.2% and is more likely to be reported on the PRAMS questionnaire than the birth certificate. We found no statistical difference in GDM prevalence between the 2 phases. Further studies are needed to understand discrepancies in reporting GDM by data source." Effect of treatment of gestational diabetes mellitus: a systematic review and meta-analysis "Ten studies involving 3,881 patients contributed to meta-analysis. Our results indicated that gestational diabetes mellitus treatment significantly reduced the risk for macrosomia (RR, 0.47; 95% CI, 0.38-0.57), large for gestational age births (RR, 0.55; 95% CI, 0.45-0.67), shoulder dystocia (RR, 0.42; 95% CI, 0.23-0.77) and gestational hypertension (RR, 0.68; 95% CI, 0.53-0.87) without causing any significant increase in the risk for small for gestational age babies." The Relation of a Woman's Impaired in Utero Growth and Association of Diabetes During Pregnancy "Small for gestational age (weight for gestational age <10th percentile, SGA) birth status and adulthood susceptibility to diabetes is well established, but the relationship to diabetes during pregnancy is incompletely understood. The authors investigated the association between women's impaired fetal growth (as measured by SGA status) and diabetes mellitus (DM) during pregnancy. ...The authors conclude that impaired fetal growth (as measured by SGA status) is a risk factor for DM during pregnancy among the leading racial/ethnic groups in the United States."

Gestational Diabetes

Diabetes recording blood sugar levels.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with the onset or first detection during pregnancy and can occur in 2 to 17.8% of all pregnancies.

Women with gestational diabetes mellitus can progress to type 2 diabetes mellitus (progression rate 6% to 92%) have high birth weight babies and suffer birth trauma.

Well-controlled class A1 gestational diabetes (fasting blood sugar less than 105 mg/dL). Recent study shows no evidence clearly supports the practice of increased fetal surveillance in these pregnancies.

Screening and Diagnosis

The following information is based upon published Australian data. .

Screening should be performed at 26–28 weeks gestation (GA 26-28).

A positive screening test result is either:

• 50-gram glucose load (morning, non-fasting) with a 1-hour venous plasma glucose level of 7.8 mmol/L or over.
• 75-gram glucose load (morning, non-fasting) with a 1-hour venous plasma glucose level of 8.0 mmol/L or over.

Positive diagnosis is made based on a 75-gram oral glucose tolerance test result of either:

• fasting (0 hour) venous plasma glucose level 5.5 mmol/L or over
• 1-hour venous plasma glucose level 10.0 mmol/L or over
• 2-hour venous plasma glucose level 8.0 mmol/L or over.

Blood glucose targets for most women with gestational diabetes

On awakening	not above 95
1 hour after a meal	not above 140
2 hours after a meal	not above 120

Table Data: NIDDK (NIH) - Gestational Diabetes

Gestational Diabetes Factors

Below are listed some known factors that can increase a woman’s chance of developing gestational diabetes.

• previous gestational diabetes
• previous elevated blood glucose level
• ethnicity — South and South-East Asian, Aboriginal or Torres Strait Islander, Pacific Islander, Maori, Middle Eastern, or non-Caucasian African women are at greater risk than other women
• age — women over 40 are at greater risk than younger women
• family history of diabetes mellitus
• pre-pregnancy obesity - body mass index of more than 30 kg/m2
• previously having a high birthweight baby - greater than 4,500 grams
• polycystic ovarian syndrome
• maternal medications - including corticosteroids or antipsychotics

Australia

Australian maternal diabetes 2014-2015

The Diabetes in pregnancy 2014–2015 report examines the short-term impact of pre-existing diabetes (type 1 or type 2) and gestational diabetes on mothers in pregnancy and their babies between 2014 and 2015. The report analyses data from the Australian Institute of Health and Welfare National Perinatal Data Collection.

• Diabetes affects nearly 1 in 10 pregnancies - In the 2-year period from 2014–2015, more than 45,000 mothers who gave birth in Australia (excluding Victoria) had diabetes, representing about 9.9% of all births recorded in the National Perinatal Data Collection (NPDC). Of those, about 40,500 (8.9%) had gestational diabetes, and 4,700 (1.0%) had pre-existing diabetes.
• Mothers with pre-existing diabetes were at highest risk of adverse effects
  • Compared with mothers with no diabetes in pregnancy, mothers with pre-existing diabetes and gestational diabetes had higher rates of caesarean section, induced labour, pre-existing and gestational hypertension, and pre-eclampsia. They also had longer antenatal and postnatal stay in hospital (5 or more days).
  • Mothers with gestational diabetes experienced complications at a lower rate than mothers with pre-existing diabetes.
• Babies of mothers with pre-existing diabetes were at highest risk of adverse effects
  • Compared with babies of mothers with gestational diabetes or no diabetes, babies of mothers with pre-existing diabetes had higher rates of pre-term birth, stillbirth, low and high birthweight, low Apgar score, resuscitation, and special care nursery/ neonatal intensive care unit admission, and stayed longer in hospital.
  • Babies of mothers with gestational diabetes had higher rates of complications than babies of mothers with no diabetes, but showed similar levels of risk as babies of mothers with no diabetes for high birthweight and low Apgar score.
• Having diabetes in pregnancy increased the risk of complications among some population groups
  • Among Aboriginal and Torres Strait Islander mothers, the incidence of some complications occurred at a greater rate among mothers with pre-existing diabetes than among mothers with no diabetes. Babies of Indigenous mothers with pre-existing and gestational diabetes also experienced greater rates of complications than babies of Indigenous mothers with no diabetes.
  • In Remote/Very remote areas, mothers with pre-existing and gestational diabetes and their babies experienced greater rates of some complications than mothers with no diabetes and their babies.

See also Reporting Diabetes pregnancy

Australia - insulin-treated diabetes by type 2015

Incidence of insulin-treated diabetes in Australia, 2015

This fact sheet published in 2017 provides the latest available national data on new cases of insulin-treated diabetes in Australia. It shows that in 2015 there were 28,775 people who began using insulin to treat their diabetes in Australia

• 63% had type 2 diabetes
• 26% (18,142) had gestational diabetes
• 9% had type 1 diabetes
• 2% had other forms of diabetes or their diabetes status was unknown.

Links: AIWH Factsheet

Adverse Pregnancy Outcome (HAPO) study

In Australia, changes to gestational diabetes mellitus (GDM) diagnostic criteria have been proposed following analysis of data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. A recent study has looked into the effects on clinical workload of implementing these diagnostic changes.

Gestational diabetes mellitus (GDM) is the most common antenatal complication in Western Australia. A recent study of the stage rural population confirmed the association of GDM with age; obesity, lower socioeconomic quintile and Asian ethnicity are also present in the rural population.

Diabetes in pregnancy: its impact on Australian women and their babies 2010

AIHW Report

• Diabetes in pregnancy is common, affecting about 1 in 20 pregnancies. Pre-existing diabetes in pregnancy affected less than 1% of pregnancies, and gestational diabetes mellitus (GDM) affected about 5% in 2005–07.
• Among Aboriginal and Torres Strait Islander mothers, pre-existing diabetes affecting pregnancy was 3 to 4 times as common, and GDM twice as common, as in non-Indigenous mothers. The rate of Type 2 diabetes in Indigenous mothers was 10 times as high.
• Mothers with pre-existing diabetes were more likely to have pre-term birth, pre-term induced labour, caesarean section, hypertension and longer stay in hospital than mothers with GDM or without diabetes in pregnancy.
• Babies of mothers with pre-existing diabetes had higher rates of stillbirth, pre-term birth, high birthweight, low Apgar score, high-level resuscitation, admission to special care nursery/neonatal intensive care unit, and longer stay in hospital than babies of mothers with GDM or without diabetes in pregnancy.

Gestational diabetes mellitus in Australia 2005-06

AIHW Report

• 2005-06, 4.6% of women aged 15-49 years who gave birth in hospital were diagnosed with GDM (more than 12,400 women and their babies)
• 15-49 year age bracket incidence increased by over 20% between 2000-01 and 2005-06.
• Risk of being diagnosed with gestational diabetes increases with age - from 1% among 15-19 year old women to 13% among women 44-49 years of age.
• Women aged 30-34 years (age group that has the most babies) accounted for over 30% of GDM cases in 2005-06.
• Women born overseas are twice the incidence rate of women born in Australia.
• Women born in Southern Asia are at particularly high risk with an incidence rate 3.4 times the rate of Australian-born women.
• Aboriginal and Torres Strait Islander women rate 1.5 times as high as other Australian women and had a higher risk across all age groups.

Links: Diabetes in pregnancy: its impact on Australian women and their babies 2010 | AIHW Report - Gestational diabetes mellitus in Australia, 2005-06

Spain

• Trends in deliveries in women with gestational diabetes in Spain, 2001-2008. "We examined trends and characteristics of deliveries in women with gestational diabetes in Spain from 2001 to 2008. There were 101,643 deliveries with gestational diabetes among 2,782,369 delivery discharges (3.6%) with no increase over time. Rate of caesarean section increased (19-24.2%) and length of stay decreased."

Diabetes

Australian trends diabetes prevalence 1990-2008

Maternal Type 1 Diabetes

Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies: a population-based cohort study

• risk of perinatal complications in overweight and obese women with and without type 1 diabetes (T1DM)
  • based on data from the Swedish Medical Birth Registry from 1998 to 2007 (3457 T1DM and 764 498 non-diabetic pregnancies)
• High pre-pregnancy BMI is an important risk factor for adverse outcome in type 1 diabetic pregnancies.
• The combined effect of both T1DM and overweight or obesity constitutes the greatest risk. It seems prudent to strive towards normal pre-pregnancy BMI in women with T1DM.

Percentage perinatal outcomes for pregnant women with or without type 1 diabetes and stratified on pre-pregnancy BMI (Modified from Table 2)

Body Mass Index	18.5 - 24.9	25 - 29.9	≥30
Large for Gestational Age
Type 1 diabetes	47	50	51
Non-diabetic	8.2	13	18
Major malformations
Type 1 diabetes	4.0	3.7	6.6
Non-diabetic	1.7	1.9	2.0
Pre-eclampsia
Type 1 diabetes	14	15	18
Non-diabetic	2.1	3.3	5.8
Preterm delivery
Type 1 diabetes	20	23	23
Non-diabetic	4.5	4.7	5.7
Perinatal mortality
Type 1 diabetes	0.85	1.3	0.97
Non-diabetic	0.32	0.47	0.72
Caesarean section
Type 1 diabetes	46	53	59
Non-diabetic	13	17	22
Neonatal overweight
Type 1 diabetes	21	24	27
Non-diabetic	3	5	8
Table Data are presented as percentages

Maternal Type 2 Diabetes

A study of maternal and neonatal outcomes in 200 Korean women with or without type 2 diabetes, showed a poorer outcome with diabetes. Diabetes results in a higher risk for primary caesarean section, pre-eclampsia, infections during pregnancy, large neonatal birth weight, large for gestational age, and macrosomia.

Links: Macrosomia

Diabetic Placenta

Maternal Type 1 diabetes can alter placental vascular development. Effects may be due to either maternal hyperglycaemia or fatal hyperinsulinaemia with high glucose and insulin shown in other systems to alter vascularity, increasing vascular endothelial growth factor (VEGF), nitric oxide (NO) and protein kinase C (PKC).

Features of the placental vessels and villi include:

• Increased angiogenesis.
• altered junctional maturity and molecular occupancy.
• increased leakiness.
• increased surface area of the capillary wall (by elongation, enlargement of diameter).
• higher branching of villous capillaries.
• disruption of the stromal structure of terminal villi.

In addition, a Russian histology study of placental villi in gestational diabetes and diabetes mellitus, showed greatest changes occurred in type 1 diabetes mellitus.

Links: placenta abnormalities

Diabetes Insipidus

Diabetes insipidus (DI) is a rare complication of pregnancy occurring in 1 in 30,000 pregnancies.

• Central diabetes insipidus - usually damage to either the pituitary gland or hypothalamus affecting anti-diuretic hormone (ADH, vasopressin} levels.
• Nephrogenic diabetes insipidus - results from genetic or chronic abnormal kidney tubules that are unable to respond to ADH.

Drugs can cause nephrogenic diabetes (lithium and some antiviral medications).

• Gestational diabetes insipidus - vasopressinase activity secreted by placental trophoblasts destroys maternal ADH.
• Primary polydipsia cause is intake of excessive fluids.

Cardiac Effects

Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development. " It is suggested that the down-regulation of genes involved in development of cardiac neural crest could contribute to the pathogenesis of maternal diabetes-induced congenital heart defects."

Links: cardiovascular

Neural Effects

Anencephaly in a fetus (GA week 18) shown by ultrasound (coronal images) complete absence of the cranial vault and brain and enlarged orbits.

Links: Anencephaly | Neural System Development

Fetal Macrosomia

Fetal macrosomia is a clinical description for a fetus that is too large, condition increases steadily with advancing gestational age and defined by a variety of birthweights. In pregnant women, anywhere between 2 - 15% have birth weights of greater than 4000 grams (4 Kg, 8 lb 13 oz).

Links: Birth Weight | Birth

Metabolic Syndrome

Obesity and insulin resistance cause Metabolic syndrome (MetS) that acts as a predictor for the risk of type 2 diabetes mellitus and cardiovascular disease.

Links: Metabolic Syndrome

Animal Models

Mouse

A recent study using a mouse diabetes model has shown that suppression of glucagon action will eliminate manifestations of diabetes.

"In conclusion, the metabolic manifestations of diabetes cannot occur without glucagon action and, once present, disappear promptly when glucagon action is abolished. Glucagon suppression should be a major therapeutic goal in diabetes."

Links: mouse

Zebrafish

Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos "Our data demonstrate that elevated glucose alone induces cardiac defects in zebrafish embryos by altering the expression pattern of tbx5, tbx20, and has2 in the heart. We also show the first evidence that cardiac looping is affected earliest during heart organogenesis."

Links: zebrafish

References

Reviews

Moore K, Stotz S, Fischl A, Beirne S, McNealy K, Abujaradeh H & Charron-Prochownik D. (2019). Pregnancy and Gestational Diabetes Mellitus (GDM) in North American Indian Adolescents and Young Adults (AYA): Implications for Girls and Stopping GDM. Curr. Diab. Rep. , 19, 113. PMID: 31686243 DOI.

Vitacolonna E, Succurro E, Lapolla A, Scavini M, Bonomo M, Di Cianni G, Di Benedetto A, Napoli A, Tumminia A, Festa C, Lencioni C, Torlone E, Sesti G, Mannino D & Purrello F. (2019). Guidelines for the screening and diagnosis of gestational diabetes in Italy from 2010 to 2019: critical issues and the potential for improvement. Acta Diabetol , 56, 1159-1167. PMID: 31396699 DOI.

Pergialiotis V, Bellos I, Hatziagelaki E, Antsaklis A, Loutradis D & Daskalakis G. (2019). Progestogens for the prevention of preterm birth and risk of developing gestational diabetes mellitus: a meta-analysis. Am. J. Obstet. Gynecol. , 221, 429-436.e5. PMID: 31132340 DOI.

Doi SAR, Furuya-Kanamori L, Toft E, Musa OAH, Islam N, Clark J & Thalib L. (2019). Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta-analysis of randomized controlled trials. Obes Rev , , . PMID: 31667980 DOI.

Ou XH, Zhu CC & Sun SC. (2019). Effects of obesity and diabetes on the epigenetic modification of mammalian gametes. J. Cell. Physiol. , 234, 7847-7855. PMID: 30536398 DOI.

Vitoratos N, Vrachnis N, Valsamakis G, Panoulis K & Creatsas G. (2010). Perinatal mortality in diabetic pregnancy. Ann. N. Y. Acad. Sci. , 1205, 94-8. PMID: 20840259 DOI.

Namak S, Lord RW, Zolotor AJ & Kramer R. (2010). Clinical inquiries: which women should we screen for gestational diabetes mellitus?. J Fam Pract , 59, 467-8. PMID: 20714459

Aleksandrov N, Audibert F, Bedard MJ, Mahone M, Goffinet F & Kadoch IJ. (2010). Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can , 32, 225-31. PMID: 20500966

Moore TR. (2010). Fetal exposure to gestational diabetes contributes to subsequent adult metabolic syndrome. Am. J. Obstet. Gynecol. , 202, 643-9. PMID: 20430355 DOI.

Hawkins JS. (2010). Glucose monitoring during pregnancy. Curr. Diab. Rep. , 10, 229-34. PMID: 20425587 DOI.

Articles

Nicklas JM, Zera CA & Seely EW. (2020). Predictors of very early postpartum weight loss in women with recent gestational diabetes mellitus. J. Matern. Fetal. Neonatal. Med. , 33, 120-126. PMID: 30032681 DOI.

Landon MB, Mele L, Varner MW, Casey BM, Reddy UM, Wapner RJ, Rouse DJ, Tita ATN, Thorp JM, Chien EK, Saade G, Grobman W, Blackwell SC & VanDorsten JP. (2020). The relationship of maternal glycemia to childhood obesity and metabolic dysfunction^‡. J. Matern. Fetal. Neonatal. Med. , 33, 33-41. PMID: 30021494 DOI.

Li P, Yin J, Zhu Y, Li S, Chen S, Sun T, Shan Z, Wang J, Shang Q, Li X, Yang W & Liu L. (2019). Association between plasma concentration of copper and gestational diabetes mellitus. Clin Nutr , 38, 2922-2927. PMID: 30661907 DOI.

Maple-Brown LJ, Brown A, Lee IL, Connors C, Oats J, McIntyre HD, Whitbread C, Moore E, Longmore D, Dent G, Corpus S, Kirkwood M, Svenson S, van Dokkum P, Chitturi S, Thomas S, Eades S, Stone M, Harris M, Inglis C, Dempsey K, Dowden M, Lynch M, Boyle J, Sayers S, Shaw J, Zimmet P & O'Dea K. (2013). Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. BMC Pregnancy Childbirth , 13, 221. PMID: 24289168 DOI.

França EL, Calderon Ide M, Vieira EL, Morceli G & Honorio-França AC. (2012). Transfer of maternal immunity to newborns of diabetic mothers. Clin. Dev. Immunol. , 2012, 928187. PMID: 22991568 DOI.

Alorainy IA, Barlas NB & Al-Boukai AA. (2010). Pictorial Essay: Infants of diabetic mothers. Indian J Radiol Imaging , 20, 174-81. PMID: 21042439 DOI.

Yogev Y, Melamed N, Chen R, Nassie D, Pardo J & Hod M. (2011). Glyburide in gestational diabetes--prediction of treatment failure. J. Matern. Fetal. Neonatal. Med. , 24, 842-6. PMID: 21067291 DOI.

Fernández-Morera JL, Rodríguez-Rodero S, Menéndez-Torre E & Fraga MF. (2010). The possible role of epigenetics in gestational diabetes: cause, consequence, or both. Obstet Gynecol Int , 2010, 605163. PMID: 21052542 DOI.

van der Ploeg HP, van Poppel MN, Chey T, Bauman AE & Brown WJ. (2011). The role of pre-pregnancy physical activity and sedentary behaviour in the development of gestational diabetes mellitus. J Sci Med Sport , 14, 149-52. PMID: 21030304 DOI.

Books

• National Collaborating Centre for Women's and Children's Health (UK). Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London: National Institute for Health and Care Excellence (UK); 2015 Feb. (NICE Guideline, No. 3.) Available from: http://www.ncbi.nlm.nih.gov/books/NBK293625/

Search Pubmed

Search Pubmed: Maternal Diabetes | Gestational Diabetes Mellitus | Gestational Diabetes | Macrosomia | Diabetic Placenta

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

• Medline Plus - diabetes and pregnancy
• NIDDK (NIH) - Gestational Diabetes
• Agency for Healthcare Research and Quality - Gestational Diabetes: A Guide for Pregnant Women
• Australia
  • Diabetes Australia
  • Diabetes indicators, Australia 2016

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

---

Cite this page: Hill, M.A. (2023, December 11) Embryology Abnormal Development - Maternal Diabetes. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Maternal_Diabetes

What Links Here?

© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G