Abnormal Development - Maternal Diabetes: Difference between revisions

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==Introduction==
==Introduction==
[[File:WDD17 infographic Gestational Diabetes.jpg|thumb|alt=WDD17 infographic Gestational Diabetes|link=http://www.worlddiabetesday.org|World Diabetes Day 17 Gestational Diabetes]]
[[File:Human- pancreatic adult islet.jpg|thumb|300px|alt=Human Pancreatic Islet|Human Pancreatic Islets (Islets of Langerhans)<ref><pubmed>18958289</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003559 PLoS ONE]</ref>]]
[[File:Human- pancreatic adult islet.jpg|thumb|300px|alt=Human Pancreatic Islet|Human Pancreatic Islets (Islets of Langerhans)<ref><pubmed>18958289</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003559 PLoS ONE]</ref>]]
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).  
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).  

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Introduction

WDD17 infographic Gestational Diabetes
World Diabetes Day 17 Gestational Diabetes
Human Pancreatic Islet
Human Pancreatic Islets (Islets of Langerhans)[1]

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).


Links: Endocrine - Pancreas Development | Macrosomia | Prenatal Diagnosis | Neonatal Diagnosis


Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | zoonotic infection | toxoplasmosis | Malaria | maternal diabetes | maternal hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | hypoxia | biological toxins | chemicals | heavy metals | air pollution | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis

Some Recent Findings

Australia - insulin-treated diabetes by type 2015
Australia - insulin-treated diabetes by type 2015
  • Proportion of insulin-treated diabetes by type (2015)[2] "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."
  • PLoS Collection - Diabetes Prevention In this Collection, we feature PLOS articles that focus on the prevention of diabetes.
  • Prevalence of Gestational Diabetes Mellitus in Korea[3] "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[4] "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 Development
  • Prevalence Estimates of Gestational Diabetes Mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010[5] "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[6] "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[7] "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."
More recent papers  
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Search term: Maternal Diabetes

<pubmed limit=5>Maternal Diabetes</pubmed>

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. [8].

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

Australia

Australia - insulin-treated diabetes by type 2015
Australia - insulin-treated diabetes by type 2015

Incidence of insulin-treated diabetes in Australia, 2015

This fact sheet published in 2017[2] 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.[9]

Gestational diabetes mellitus (GDM) is the most common antenatal complication in Western Australia. A recent study of the stage rural population[10] 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[11]

  • 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[12]

  • 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.[13] "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 19990-2008.jpg

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[14]

  • 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[14])

              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.[15] 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).[16][17]

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).[18]
  • higher branching of villous capillaries.[18]
  • disruption of the stromal structure of terminal villi.[18]


In addition, a Russian histology study of placental villi in gestational diabetes and diabetes mellitus, showed greatest changes occurred in type 1 diabetes mellitus.[19]


Links: Placenta Abnormalities

Cardiac Effects

Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development.[20] " 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 System Development

Neural Effects

Anencephaly ultrasound.jpg

Anencephaly in a fetus (GA week 18) shown by ultrasound (coronal images) complete absence of the cranial vault and brain and enlarged orbits.[21]

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

Animal Models

Mouse

A recent study using a mouse diabetes model[22] 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

Zebrafish

Elevated glucose induces congenital heart defects by altering the expression of tbx5, tbx20, and has2 in developing zebrafish embryos [23] "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

References

  1. <pubmed>18958289</pubmed>| PLoS ONE
  2. 2.0 2.1 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.
  3. <pubmed>27046149</pubmed>
  4. <pubmed>26020623</pubmed>| PLoS One.
  5. <pubmed>24945238</pubmed>| Prev Chronic Dis.
  6. <pubmed>24658089</pubmed>
  7. <pubmed>24557833</pubmed>
  8. AIHW 2010. Diabetes in pregnancy: its impact on Australian women and their babies. Diabetes series no. 14. Cat. no. CVD 52. Canberra: AIHW | PDF
  9. <pubmed>21039377</pubmed>
  10. <pubmed>25171091</pubmed>
  11. 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
  12. 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
  13. <pubmed>21035890</pubmed>
  14. 14.0 14.1 <pubmed>22334581</pubmed>| BMJ Open.
  15. <pubmed>28122420</pubmed>
  16. <pubmed>21418381</pubmed>
  17. <pubmed>19563553</pubmed>
  18. 18.0 18.1 18.2 <pubmed>22317894</pubmed>
  19. <pubmed>22462069</pubmed>
  20. <pubmed>17967198</pubmed>
  21. <pubmed>21042439</pubmed>| Indian J Radiol Imaging.
  22. <pubmed>22891336</pubmed>
  23. <pubmed>20306498</pubmed>]

Journals

Reviews

20840259 <pubmed>20714459</pubmed> <pubmed>20500966</pubmed> <pubmed>20430355</pubmed> 20425587

Articles

<pubmed></pubmed> <pubmed></pubmed> <pubmed>24289168</pubmed> <pubmed>22991568</pubmed> <pubmed>21042439</pubmed> <pubmed>21067291</pubmed> <pubmed>21052542</pubmed> <pubmed>21030304</pubmed>


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/

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Cite this page: Hill, M.A. (2024, March 28) Embryology Abnormal Development - Maternal Diabetes. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Maternal_Diabetes

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