Abnormal Development - Maternal Diabetes: Difference between revisions

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==Some Recent Findings==
==Some Recent Findings==
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Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Maternal+Diabetes ''Maternal Diabetes'']


[[Talk:Abnormal_Development_-_Maternal_Diabetes|Recent References]] | [[#References|References]]
<pubmed limit=5>Maternal Diabetes</pubmed>
 
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==Gestational Diabetes==
==Gestational Diabetes==
[[File:Diabetes record blood sugar.jpg|thumb|Diabetes recording blood sugar levels.]]
[[File:Diabetes record blood sugar.jpg|thumb|Diabetes recording blood sugar levels.]]

Revision as of 14:33, 2 June 2013

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

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.

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.


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

  • NIH Consensus Development Conference: Diagnosing Gestational Diabetes Mellitus Bethesda, Maryland March 4–6, 2013.
  • Diagnostic and Prognostic Performances Over 9 Years of a Selective Screening Strategy for Gestational Diabetes Mellitus[2] "We aimed to evaluate a selective screening strategy for gestational diabetes mellitus (GDM) based on the presence of risk factors: BMI ≥25 kg/m(2), age ≥35 years, family history of diabetes, personal history of GDM, or birth of a child with macrosomia. ...The presence of risk factors increased during the last decade. This condition is predictive of GDM and GDM-related events. However, a selective screening would lead to missing one-third of the women with GDM who, even without risk factors, had more events than women without GDM. Therefore, these data stand against the present selective screening currently proposed in the French guidelines."
  • Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies: a population-based cohort study[3] To assess the 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.
  • The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus[4] "Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas. Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. ...The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas. It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi."
  • Diabetes in pregnancy: its impact on Australian women and their babies 2010 [5] "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.
  • Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy[6] "Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are pathological conditions associated with placenta vascular dysfunction coursing with metabolic changes at the fetoplacental microvascular and macrovascular endothelium. These alterations are seen as abnormal expression and activity of the cationic amino acid transporters and endothelial nitric oxide synthase isoform, that is, the "endothelial L-arginine/nitric oxide signalling pathway." Several studies suggest that the endogenous nucleoside adenosine along with insulin, and potentially arginases, are factors involved in GDM-, but much less information regards their role in OP-associated placental vascular alterations. There is convincing evidence that GDM and OP prone placental endothelium to an "altered metabolic state" leading to fetal programming evidenced at birth, a phenomenon associated with future development of chronic diseases. In this paper it is suggested that this pathological state could be considered as a metabolic marker that could predict occurrence of diseases in adulthood, such as cardiovascular disease, obesity, diabetes mellitus (including gestational diabetes), and metabolic syndrome."

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. [7].

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

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.[8]

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

AIHW Report[5]

  • 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[9]

  • 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.[10] "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[3]

  • 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[3])

              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

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).[11][12]

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).[4]
  • higher branching of villous capillaries.[4]
  • disruption of the stromal structure of terminal villi.[4]


In addition, a Russian histology study of placental villi in gestational diabetes and diabetes mellitus, showed greatest changes occurred in type 1 diabetes mellitus.[13]


Links: Placenta Abnormalities

Cardiac Effects

Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development.[14] " 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.[15]

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

Animal Models

Mouse

A recent study using a mouse diabetes model[16] 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 [17] "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. <pubmed>23150287</pubmed>
  3. 3.0 3.1 3.2 <pubmed>22334581</pubmed>| BMJ Open.
  4. 4.0 4.1 4.2 4.3 <pubmed>22317894</pubmed>
  5. 5.0 5.1 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
  6. <pubmed>22144986</pubmed>
  7. AIHW 2010. Diabetes in pregnancy: its impact on Australian women and their babies. Diabetes series no. 14. Cat. no. CVD 52. Canberra: AIHW | PDF
  8. <pubmed>21039377</pubmed>
  9. 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
  10. <pubmed>21035890</pubmed>
  11. <pubmed>21418381</pubmed>
  12. <pubmed>19563553</pubmed>
  13. <pubmed>22462069</pubmed>
  14. <pubmed>17967198</pubmed>
  15. <pubmed>21042439</pubmed>| Indian J Radiol Imaging.
  16. <pubmed>22891336</pubmed>
  17. <pubmed>20306498</pubmed>]

Journals

Reviews

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

Articles

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

Search Pubmed

November 2010 "Maternal Diabetes"

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

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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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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G