The Effect of Intensified Conventional Insulin Therapy before and during Pregnancy on the Malformation Rate in Offspring of Diabetic Mothers

Fuhrmann, K; Reiher, H; Semmler, K; Glöckner, E

doi:10.1055/s-0029-1210327

Cited by 122 publications

(18 citation statements)

References 4 publications

(5 reference statements)

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“…Furthermore, the risk of having a major birth defect was directly proportional to the degree of the blood glucose control in mothers during the first trimester of pregnancy. Fuhrmann et al [18] and Kitzmiller et al [17] similarly found that pregestational control of diabetes was associated with a significant reduction in birth defects.…”

Section: Stringent Glucose Control and Birth Defectsmentioning

confidence: 97%

“…Studies show that stringent glucose control prior to or early in pregnancy can significantly reduce the incidence of birth defects [12][13][14][15][16][17][18]. Mironiuk et al [12] followed the birth outcomes of 170 mothers with type 1 diabetes and compared their outcomes to those of a control group consisting of 56 mothers with GDM and 26,368 healthy women.…”

Section: Stringent Glucose Control and Birth Defectsmentioning

confidence: 99%

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Diabetes-Induced Birth Defects: What Do We Know? What Can We Do?

Reece

2011

Curr Diab Rep

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Birth defects are the leading cause of infant mortality in the United States, which has one of the highest infant mortality rates in the developed world. Many of these birth defects can be attributed to pre-existing, or pregestational, diabetes in pregnancy, which significantly increases a mother's risk of having a child with a major birth defect. Strict preconceptional and early pregnancy glucose control, supplementation with multivitamins and fatty acids, and lower glycemic dietary management have been shown to reduce the incidence of birth defects in experimental and epidemiologic studies. However, because more than half of pregnancies are unplanned, these methods are not generalizable across the population. Thus, better interventions are urgently needed. Based on what we know about the molecular pathophysiology of diabetic embryopathy, our laboratory and others are developing interventions against to key molecular targets in this multifactorial disease process.

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Section: Stringent Glucose Control and Birth Defectsmentioning

confidence: 97%

Section: Stringent Glucose Control and Birth Defectsmentioning

confidence: 99%

Diabetes-Induced Birth Defects: What Do We Know? What Can We Do?

Reece

2011

Curr Diab Rep

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“…Hyperglycemia during the periconceptional period and later in gestation is a major teratogenic factor 10, 138-141 causing a range of adverse outcomes from fetal death, to congenital anomalies, to accelerated fetal growth and delivery complications, to higher rates of metabolic syndrome in adults due to altered in utero programming 142, 143 .…”

Section: Future Perspectives and Clinical Relevancementioning

confidence: 99%

Decoding the oxidative stress hypothesis in diabetic embryopathy through proapoptotic kinase signaling

Yang¹,

Reece²,

Wang³

et al. 2015

American Journal of Obstetrics and Gynecology

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Maternal diabetes-induced birth defects occur in 6-10% of babies born to mothers with pregestational diabetes, representing a significant maternal-fetal health problem. Currently, these congenital malformations represent a significant maternal-fetal medicine issue, but are likely to create an even greater public health threat as 3 million women of reproductive age (19-44 years) have diabetes in the United States alone, and this number is expected to double by 2030. Neural tube defects (NTDs) and congenital heart defects are the most common types of birth defects associated with maternal diabetes. Animal studies have revealed that embryos under hyperglycemic conditions exhibit high levels of oxidative stress resulting from enhanced production of reactive oxygen species and impaired antioxidant capability. Oxidative stress activates a set of pro-apoptotic kinase signaling intermediates leading to abnormal cell death in the embryonic neural tube, which causes NTD formation. Work in animal models also has revealed that maternal diabetes triggers a series of signaling intermediates: protein kinase C (PKC) isoforms, PKCα, βII and δ; apoptosis signal-regulating kinase 1 (ASK1), c-Jun-N-terminal kinase 1/2 (JNK1/2), caspase and apoptosis. Specifically, maternal diabetes in rodent models activates the pro-apoptotic unfolded protein response and endoplasmic reticulum (ER) stress. A reciprocal causation between JNK1/2 activation and ER stress exists in diabetic embryopathy. Molecular studies further demonstrate that deletion of the genes for PKCα, Ask1, Jnk1 or Jnk2 abolishes maternal diabetes-induced neural progenitor apoptosis and ameliorates NTD formation. Similar preventive effects are also observed when ASK1, JNK1/2 or ER stress is inhibited. Cell membrane stabilizers and antioxidant supplements are also effective in prevention of diabetes-induced birth defects. Mechanistic studies have revealed important insights into our understanding the cause of diabetic embryopathy and have provided a basis for future interventions against birth defects or other pregnancy complications associated with maternal diabetes. The knowledge of a molecular pathway map identified in animal studies has created unique opportunities to identify molecular targets for therapeutic intervention.

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“…Uncontrolled diabetic status throughout the pregnancy has been associated with a spectrum of disorders involving neural tube defects (NTDs), including spina bifida, anencephaly, encephalocele, holoprosencephaly, and cardiovascular [122–124] kidney, and skeletal system defects in addition to growth delay and miscarriage [116]. In fact, any organ can be affected, and 8% to 12% of diabetic pregnant women presented malformed fetuses [125].…”

Section: Diabetes-induced Teratogenesismentioning

confidence: 99%

Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

Damasceno

Netto

Iessi

et al. 2014

BioMed Research International

130

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Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

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The Effect of Intensified Conventional Insulin Therapy before and during Pregnancy on the Malformation Rate in Offspring of Diabetic Mothers

Cited by 122 publications

References 4 publications

Diabetes-Induced Birth Defects: What Do We Know? What Can We Do?

Diabetes-Induced Birth Defects: What Do We Know? What Can We Do?

Decoding the oxidative stress hypothesis in diabetic embryopathy through proapoptotic kinase signaling

Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

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