Abnormal Development - Maternal Diabetes
|Embryology - 28 Feb 2017 Expand to Translate|
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|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.|
- 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 Australia
- 3.4 Spain
- 4 Diabetes
- 5 Maternal Type 1 Diabetes
- 6 Maternal Type 2 Diabetes
- 7 Diabetic Placenta
- 8 Cardiac Effects
- 9 Neural Effects
- 10 Fetal Macrosomia
- 11 Animal Models
- 12 References
- 13 External Links
- 14 Glossary Links
Diabetes during pregnancy in any form, whether pregestational (type 1 or type 2) or gestational, 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 shows an automated computer PubMed search using the listed sub-heading term.
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.
Ensieh Nasli-Esfahani, Farshad Farzadfar, Marjan Kouhnavard, Robabeh Ghodssi-Ghassemabadi, Alireza Khajavi, Maryam Peimani, Rezvan Razmandeh, Mahboobeh Vala, Gita Shafiee, Camelia Rambod, Mahnaz Sanjari, Maryam Aalaa, Maryam Ghodsi, Farideh Razi, Fatemeh Bandarian, Bagher Larijani Iran diabetes research roadmap (IDRR) study: a preliminary study on diabetes research in the world and Iran. J Diabetes Metab Disord: 2017, 16;9 PubMed 28239599
Kai P Law, Ting-Li Han, Xun Mao, Hua Zhang Tryptophan and purine metabolites are consistently upregulated in the urinary metabolome of patients diagnosed with gestational diabetes mellitus throughout pregnancy: A longitudinal metabolomics study of Chinese pregnant women part 2. Clin. Chim. Acta: 2017; PubMed 28238935
S F Ehrlich, M M Hedderson, S D Brown, B Sternfeld, L Chasan-Taber, J Feng, J Adams, J Ching, Y Crites, C P Quesenberry, A Ferrara Moderate intensity sports and exercise is associated with glycaemic control in women with gestational diabetes. Diabetes Metab.: 2017; PubMed 28238600
Annett Helleskov Rasmussen, Sonja Wehberg, Jesper Fenger-Groen, Henrik Thybo Christesen Retrospective Evaluation of a National Guideline to Prevent Neonatal Hypoglycemia. Pediatr Neonatol: 2017; PubMed 28237510
Jigal Haas, Yaakov Bentov Should metformin be included in fertility treatment of PCOS patients? Med. Hypotheses: 2017, 100;54-58 PubMed 28236849
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
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
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."
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).
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 Development
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 Development
- Raphaël Scharfmann, Xiangwei Xiao, Harry Heimberg, Jacques Mallet, Philippe Ravassard Beta cells within single human islets originate from multiple progenitors. PLoS ONE: 2008, 3(10);e3559 PubMed 18958289 | PLoS ONE
- 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.
- Bo Kyung Koo, Joon Ho Lee, Jimin Kim, Eun Jin Jang, Chang-Hoon Lee Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance Database Study. PLoS ONE: 2016, 11(4);e0153107 PubMed 27046149
- Jacqueline Gürke, Frank Hirche, René Thieme, Elisa Haucke, Maria Schindler, Gabriele I Stangl, Bernd Fischer, Anne Navarrete Santos Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy. PLoS ONE: 2015, 10(5);e0127465 PubMed 26020623 | PLoS One.
- Carla L DeSisto, Shin Y Kim, Andrea J Sharma Prevalence estimates of gestational diabetes mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010. Prev Chronic Dis: 2014, 11;E104 PubMed 24945238 | Prev Chronic Dis.
- Nalinee Poolsup, Naeti Suksomboon, Muhammad Amin Effect of treatment of gestational diabetes mellitus: a systematic review and meta-analysis. PLoS ONE: 2014, 9(3);e92485 PubMed 24658089
- AIHW 2010. Diabetes in pregnancy: its impact on Australian women and their babies. Diabetes series no. 14. Cat. no. CVD 52. Canberra: AIHW | PDF
- Jeff R Flack, Glynis P Ross, Suyen Ho, Aidan McElduff Recommended changes to diagnostic criteria for gestational diabetes: impact on workload. Aust N Z J Obstet Gynaecol: 2010, 50(5);439-43 PubMed 21039377
- Andrew B Kirke, Sharon F Evans, Barry N J Walters Gestational diabetes in a rural, regional centre in south Western Australia: predictors of risk. Rural Remote Health: 2014, 14(3);2667 PubMed 25171091
- Australian Institute of Health and Welfare 2010. Diabetes in pregnancy: its impact on Australian women and their babies. Diabetes series no. 14. Cat. no. CVD 52. Canberra: AIHW. AIHW | PDF
- AIHW: Templeton M & Pieris-Caldwell I 2008. Gestational diabetes mellitus in Australia, 2005–06. Diabetes series no. 10. Cat. no. CVD 44. Canberra: AIHW. AIHW Report - Gestational diabetes mellitus in Australia, 2005-06
- Ana Lopez-de-Andres, Pilar Carrasco-Garrido, Angel Gil-de-Miguel, Valentín Hernandez-Barrera, Rodrigo Jiménez-García Trends in deliveries in women with gestational diabetes in Spain, 2001-2008. Diabetes Res. Clin. Pract.: 2011, 91(2);e27-9 PubMed 21035890
- Martina Persson, Dharmintra Pasupathy, Ulf Hanson, Magnus Westgren, Mikael Norman Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies: a population-based cohort study. BMJ Open: 2012, 2(1);e000601 PubMed 22334581 | BMJ Open.
- Hye-Jung Jang, Hee-Sook Kim, Sung-Hoon Kim Maternal and neonatal outcomes in Korean women with type 2 diabetes. Korean J. Intern. Med.: 2017; PubMed 28122420
- Lopa Leach Placental vascular dysfunction in diabetic pregnancies: intimations of fetal cardiovascular disease? Microcirculation: 2011, 18(4);263-9 PubMed 21418381
- Lopa Leach, Alice Taylor, Flavia Sciota Vascular dysfunction in the diabetic placenta: causes and consequences. J. Anat.: 2009, 215(1);69-76 PubMed 19563553
- M Jirkovská, T Kučera, J Kaláb, M Jadrníček, V Niedobová, J Janáček, L Kubínová, M Moravcová, Z Zižka, V Krejčí The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus. Placenta: 2012, 33(5);343-51 PubMed 22317894
- E A Dubova, K A Pavlov, R M Yesayan, M N Nagovitsyna, O N Tkacheva, M V Shestakova, A I Shchegolev Morphometric characteristics of placental villi in pregnant women with diabetes. Bull. Exp. Biol. Med.: 2011, 151(5);650-4 PubMed 22462069
- Srinivasan Dinesh Kumar, S Thameem Dheen, Samuel Sam Wah Tay Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development. Cardiovasc Diabetol: 2007, 6;34 PubMed 17967198
- Ibrahim A Alorainy, Nauman B Barlas, Amer A Al-Boukai Pictorial Essay: Infants of diabetic mothers. Indian J Radiol Imaging: 2010, 20(3);174-81 PubMed 21042439 | Indian J Radiol Imaging.
- Young Lee, Eric D Berglund, May-yun Wang, Xiaorong Fu, Xinxin Yu, Maureen J Charron, Shawn C Burgess, Roger H Unger Metabolic manifestations of insulin deficiency do not occur without glucagon action. Proc. Natl. Acad. Sci. U.S.A.: 2012, 109(37);14972-6 PubMed 22891336
- Jintao Liang, Yonghao Gui, Wei Wang, Shan Gao, Jing Li, Houyan Song Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos. Birth Defects Res. Part A Clin. Mol. Teratol.: 2010, 88(6);480-6 PubMed 20306498 ]
20840259 Shahla Namak, Richard W Lord, Adam J Zolotor, Rochelle Kramer Clinical inquiries: which women should we screen for gestational diabetes mellitus? J Fam Pract: 2010, 59(8);467-8 PubMed 20714459
Nikolay Aleksandrov, François Audibert, Marie-Josée Bedard, Michèle Mahone, François Goffinet, Isaac-Jacques Kadoch Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can: 2010, 32(3);225-31 PubMed 20500966
Thomas R Moore Fetal exposure to gestational diabetes contributes to subsequent adult metabolic syndrome. Am. J. Obstet. Gynecol.: 2010, 202(6);643-9 PubMed 20430355
Louise J Maple-Brown, Alex Brown, I-Lynn Lee, Christine Connors, Jeremy Oats, Harold D McIntyre, Cherie Whitbread, Elizabeth Moore, Danielle Longmore, Glynis Dent, Sumaria Corpus, Marie Kirkwood, Stacey Svenson, Paula van Dokkum, Sridhar Chitturi, Sujatha Thomas, Sandra Eades, Monique Stone, Mark Harris, Chrissie Inglis, Karen Dempsey, Michelle Dowden, Michael Lynch, Jacqueline Boyle, Sue Sayers, Jonathan Shaw, Paul Zimmet, Kerin O'Dea Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. BMC Pregnancy Childbirth: 2013, 13;221 PubMed 24289168
Eduardo Luzía França, Iracema de Mattos Paranhos Calderon, Elisa Lima Vieira, Glilciane Morceli, Adenilda Cristina Honorio-França Transfer of maternal immunity to newborns of diabetic mothers. Clin. Dev. Immunol.: 2012, 2012;928187 PubMed 22991568
Ibrahim A Alorainy, Nauman B Barlas, Amer A Al-Boukai Pictorial Essay: Infants of diabetic mothers. Indian J Radiol Imaging: 2010, 20(3);174-81 PubMed 21042439
Yariv Yogev, Nir Melamed, Rony Chen, Daniel Nassie, Joseph Pardo, Moshe Hod Glyburide in gestational diabetes--prediction of treatment failure. J. Matern. Fetal. Neonatal. Med.: 2011, 24(6);842-6 PubMed 21067291
J L Fernández-Morera, S Rodríguez-Rodero, E Menéndez-Torre, M F Fraga The possible role of epigenetics in gestational diabetes: cause, consequence, or both. Obstet Gynecol Int: 2010, 2010;605163 PubMed 21052542
Hidde P van der Ploeg, Mireille N M van Poppel, Tien Chey, Adrian E Bauman, Wendy J Brown The role of pre-pregnancy physical activity and sedentary behaviour in the development of gestational diabetes mellitus. J Sci Med Sport: 2011, 14(2);149-52 PubMed 21030304
- 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/
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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
- Australia - Diabetes indicators, Australia 2016
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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Maternal Diabetes. Retrieved February 28, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Maternal_Diabetes
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G