Talk:Abnormal Development - Maternal Diabetes

Original page - http://embryology.med.unsw.edu.au/Defect/maternaldiabetes.htm

2010

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

Liang J, Gui Y, Wang W, Gao S, Li J, Song H. Birth Defects Res A Clin Mol Teratol. 2010 Jun;88(6):480-6.

BACKGROUND: Maternal diabetes increases the risk of congenital heart defects in infants, and hyperglycemia acts as a major teratogen. Multiple steps of cardiac development, including endocardial cushion morphogenesis and development of neural crest cells, are challenged under elevated glucose conditions. However, the direct effect of hyperglycemia on embryo heart organogenesis remains to be investigated.

METHODS: Zebrafish embryos in different stages were exposed to D-glucose for 12 or 24 hr to determine the sensitive window during early heart development. In the subsequent study, 6 hr post-fertilization embryos were treated with either 25 mmol/liter D-glucose or L-glucose for 24 hr. The expression of genes was analyzed by whole-mount in situ hybridization.

RESULTS: The highest incidence of cardiac malformations was found during 6-30 hpf exposure periods. After 24 hr exposure, D-glucose-treated embryos exhibited significant developmental delay and diverse cardiac malformations, but embryos exposed to L-glucose showed no apparent phenotype. Further investigation of the origin of heart defects showed that cardiac looping was affected earliest, while the specification of cardiac progenitors and heart tube assembly were complete. Moreover, the expression patterns of tbx5, tbx20, and has2 were altered in the defective hearts.

CONCLUSIONS: 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. These research results are important for devising preventive and therapeutic strategies aimed at reducing the occurrence of congenital heart defects in diabetic pregnancy.

PMID: 20306498 http://www.ncbi.nlm.nih.gov/pubmed/20306498

The impact of gestational diabetes mellitus on pregnancy outcome comparing different cut-off criteria for abnormal glucose tolerance

Acta Obstet Gynecol Scand. 2010 Nov 5. [Epub ahead of print]

Anderberg E, Källén K, Berntorp K.

Department of Obstetrics and Gynecology in Lund, Skåne University Hospital, Lund University, Sweden.

Abstract Objective. To examine pregnancy outcomes in relation to different categories of glucose tolerance during pregnancy. Design. Prospective observational cohort study. Setting. Patient recruitment and data collection were performed in four delivery departments in southern Sweden. Population. Women delivering during 2003-2005; 306 with gestational diabetes mellitus, 744 with gestational impaired glucose tolerance and 329 randomly selected controls. Methods. All women were offered a 75 g oral glucose tolerance test during pregnancy. On the basis of their capillary 2-hour plasma glucose concentrations, three groups were identified: gestational diabetes mellitus (>10.0 mmol/l), gestational impaired glucose tolerance (8.6-9.9 mmol/l) and controls (<8.6 mmol/l). Data for the groups were compared using a population-based database. Main outcome measures. Maternal and fetal outcomes. Results. For the gestational diabetes mellitus group, adjusted odds ratios (95% confidence intervals) for hypertensive disorders during pregnancy and induction of labor and emergency cesarean section were 2.7 (1.3-5.8), 3.1 (1.8-5.2) and 2.5 (1.5-4.4), respectively; and for Apgar score <7 at 5 minutes, need for neonatal intensive care >1 day and large-for-gestational age infant were 9.6 (1.2-78.0), 5.2 (2.8-9.6) and 2.5 (1.3-5.1), respectively. The increases in odds ratios for the gestational impaired glucose tolerance group were less pronounced but still significant for hypertension during pregnancy, induction of labor, large-for-gestational age infant and use of neonatal intensive care >1 day, with odds ratios (95% confidence interval) 2.0 (1.0-4.1), 1.8 (1.1-3.0), 2.1 (1.1-3.9) and 2.1 (1.1-3.8), respectively. Conclusions. These data indicate that even limited degrees of maternal hyperglycemia may affect the outcome of pregnancy.

PMID: 21050147 http://www.ncbi.nlm.nih.gov/pubmed/21050147

Sonographic Evaluation and the Pregnancy Complicated by Diabetes

Curr Diab Rep. 2010 Nov 3. [Epub ahead of print]

McNamara JM, Odibo AO.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes-Jewish Plaza, 5th Floor Maternity Building, Campus Box 8064, Saint Louis, MO, 63110, USA, mcnamaraj@wudosis.wustl.edu. Abstract Sonography is a fundamental tool in the management of pregnancies affected by maternal diabetes. Purposeful use of ultrasound in each trimester provides an invaluable amount of information about the developing fetus including gestational age and growth patterns, anatomical structure and function, assessment of fetal well-being, and prediction of adverse outcome. There are great ongoing research efforts in this field of prenatal diagnosis and management, yet even more are needed.

PMID: 21046292 http://www.ncbi.nlm.nih.gov/pubmed/21046292

Recommended changes to diagnostic criteria for gestational diabetes: Impact on workload

Aust N Z J Obstet Gynaecol. 2010 Oct;50(5):439-43. doi: 10.1111/j.1479-828X.2010.01218.x. Epub 2010 Sep 1.

Flack JR, Ross GP, Ho S, McElduff A.

Diabetes Centre, Bankstown-Lidcombe Hospital Department of Medicine, University of NSW, Bankstown Department of Endocrinology, Royal North Shore Hospital Discipline of Medicine, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia. Abstract Background: Gestational diabetes mellitus (GDM) is recognised as a significant problem in pregnancy. Changes to GDM diagnostic criteria have been proposed following analysis of data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. We sought to assess the impact on the workload for GDM management in Australia that would occur if these changes were adopted. Aim: To assess the impact on health professional workload, specifically management of the number of additional women who would be diagnosed with GDM, should the newly recommended diagnostic criteria be adopted in Australia. Methods: We analysed oral glucose tolerance test results undertaken in pregnant women at two large pathology services in South West and Northern Sydney. We calculated GDM rates using current Australasian Diabetes in Pregnancy Society (ADIPS) Australian Criteria and the rates using the proposed new criteria. Results: These workload data compare ADIPS and proposed International Association of Diabetes and Pregnancy Study Groups Criteria. In a high-risk population examined in two time periods, the estimated increase in workload was 29.0% (based on November 2005 to August 2007 data) and 31.9% (based on September 2007 to August 2009 data). Data from Northern Sydney indicated a 21.7% increased workload (based on September 1998 to July 2009 data). Conclusions: If the newly recommended changes to the diagnostic criteria for GDM are implemented in Australia, we may need to change the way we currently structure our services to manage GDM, to cope with the workload impact of the significantly increased number of women who would require management. In some units this change will be substantial.

Gestational diabetes mellitus: why screen and how to diagnose

Karagiannis T, Bekiari E, Manolopoulos K, Paletas K, Tsapas A. Hippokratia. 2010 Jul;14(3):151-4. PMID: 20981162

Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development

Kumar SD, Dheen ST, Tay SS. Cardiovasc Diabetol. 2007 Oct 30;6:34. PMID: 17967198

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