Abnormal Development - Maternal Diabetes
|Embryology - 26 Jan 2020 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Gestational Diabetes
- 3.1 Screening and Diagnosis
- 3.2 Blood glucose targets for most women with gestational diabetes
- 3.3 Gestational Diabetes Factors
- 3.4 Australia
- 3.5 Spain
- 4 Diabetes
- 5 Maternal Type 1 Diabetes
- 6 Maternal Type 2 Diabetes
- 7 Diabetic Placenta
- 8 Diabetes Insipidus
- 9 Cardiac Effects
- 10 Neural Effects
- 11 Fetal Macrosomia
- 12 Metabolic Syndrome
- 13 Animal Models
- 14 References
- 15 External Links
- 16 Glossary Links
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).
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
|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.
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
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
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
- 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
- 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
- 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."
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.
|Body Mass Index||18.5 - 24.9||25 - 29.9||≥30|
|Large for Gestational Age|
|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
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 (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.
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
Anencephaly in a fetus (GA week 18) shown by ultrasound (coronal images) complete absence of the cranial vault and brain and enlarged orbits.
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).
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
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
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
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- Lyu Y, Jia S, Wang S, Wang T, Tian W & Chen G. (2020). Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring. J. Cell. Physiol. , 235, 3519-3528. PMID: 31595494 DOI.
- Yu Y, Arah OA, Liew Z, Cnattingius S, Olsen J, Sørensen HT, Qin G & Li J. (2019). Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up. BMJ , 367, l6398. PMID: 31801789 DOI.
- Wang X, Lu J, Xie W, Lu X, Liang Y, Li M, Wang Z, Huang X, Tang M, Pfaff DW, Tang YP & Yao P. (2019). Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2. Proc. Natl. Acad. Sci. U.S.A. , , . PMID: 31685635 DOI.
- Blotsky AL, Rahme E, Dahhou M, Nakhla M & Dasgupta K. (2019). Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study. CMAJ , 191, E410-E417. PMID: 30988041 DOI.
- Australian Institute of Health and Welfare 2019. Incidence of insulin-treated diabetes in Australia 2017. Cat. no. CDK 11. Canberra: AIHW.
- Nattero-Chávez L, Luque-Ramírez M & Escobar-Morreale HF. (2019). Systemic endocrinopathies (thyroid conditions and diabetes): impact on postnatal life of the offspring. Fertil. Steril. , 111, 1076-1091. PMID: 31155115 DOI.
- Liao Y, Xu GF, Jiang Y, Zhu H, Sun LJ, Peng R & Luo Q. (2018). Comparative proteomic analysis of maternal peripheral plasma and umbilical venous plasma from normal and gestational diabetes mellitus pregnancies. Medicine (Baltimore) , 97, e12232. PMID: 30200149 DOI.
- Lund A, Ebbing C, Rasmussen S, Kiserud TW & Kessler J. (2018). Maternal diabetes alters the development of ductus venosus shunting in the fetus. Acta Obstet Gynecol Scand , , . PMID: 29752712 DOI.
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- Zeki R, Wang AY, Lui K, Li Z, Oats JJN, Homer CSE & Sullivan EA. (2018). 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-based retrospective cohort study. BMJ Paediatr Open , 2, e000224. PMID: 29637191 DOI.
- AIHW 2017. Incidence of insulin-treated diabetes in Australia, 2015. Diabetes series no. 27. Cat. no. CVD 78. Canberra: AIHW. Viewed 20 February 2017 http://www.aihw.gov.au/publication-detail/?id=60129558632.
- Zhao J, Hakvoort TBM, Ruijter JM, Jongejan A, Koster J, Swagemakers SMA, Sokolovic A & Lamers WH. (2017). Maternal diabetes causes developmental delay and death in early-somite mouse embryos. Sci Rep , 7, 11714. PMID: 28916763 DOI.
- Koo BK, Lee JH, Kim J, Jang EJ & Lee CH. (2016). Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance Database Study. PLoS ONE , 11, e0153107. PMID: 27046149 DOI.
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- AIHW 2010. Diabetes in pregnancy: its impact on Australian women and their babies. Diabetes series no. 14. Cat. no. CVD 52. Canberra: AIHW | PDF
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- Medline Plus - diabetes and pregnancy
- NIDDK (NIH) - Gestational Diabetes
- Agency for Healthcare Research and Quality - Gestational Diabetes: A Guide for Pregnant Women
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