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Diabetic Embryopathy
Janice L. B. Byrne, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Pathology

        • Clinical Issues

          TERMINOLOGY

          • Definitions

            • Pregestational diabetes (type I or II): Diabetes mellitus diagnosis predates pregnancy
            • Gestational diabetes mellitus (GDM): Any degree of glucose intolerance initially diagnosed during pregnancy
              • Diagnosis by oral glucose tolerance test from 24-28 weeks gestation
              • GDM, by definition, resolves following pregnancy, although recurrence in subsequent pregnancies is common
                • Increased risk of developing type II diabetes (40-50% within 10 years)
              • Controversy exists regarding risk of anomalies in GDM
                • Anomalies in GDM may reflect undiagnosed type II diabetic

          IMAGING

          • General Features

            • Ultrasonographic Findings

              • Imaging Recommendations

                DIFFERENTIAL DIAGNOSIS

                  PATHOLOGY

                  • General Features

                    • Staging, Grading, & Classification

                      • Microscopic Features

                        CLINICAL ISSUES

                        • Presentation

                          • Natural History & Prognosis

                            • Treatment

                              Selected References

                              1. Bohuslavova R et al: Gene expression profiling of changes induced by maternal diabetes in the embryonic heart. Reprod Toxicol. 57:147-56, 2015
                              2. Dong D et al: New development of the yolk sac theory in diabetic embryopathy: molecular mechanism and link to structural birth defects. Am J Obstet Gynecol. 214(2): 192-202, 2015
                              3. Dong D et al: Maternal diabetes triggers DNA damage and DNA damage response in neurulation stage embryos through oxidative stress. Biochem Biophys Res Commun. 467(2):407-12, 2015
                              4. Gabbay-Benziv R et al: Birth defects in pregestational diabetes: Defect range, glycemic threshold and pathogenesis. World J Diabetes. 6(3):481-8, 2015
                              5. López-Escobar B et al: The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye. Dis Model Mech. 8(2):157-68, 2015
                              6. Mitanchez D et al: The offspring of the diabetic mother--short- and long-term implications. Best Pract Res Clin Obstet Gynaecol. 29(2):256-69, 2015
                              7. Ornoy A et al: Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Res C Embryo Today. 105(1):53-72, 2015
                              8. Wang F et al: Advances in revealing the molecular targets downstream of oxidative stress-induced proapoptotic kinase signaling in diabetic embryopathy. Am J Obstet Gynecol. 213(2):125-34, 2015
                              9. Wang F et al: Oxidative stress is responsible for maternal diabetes-impaired transforming growth factor beta signaling in the developing mouse heart. Am J Obstet Gynecol. 212(5):650.e1-11, 2015
                              10. Wang F et al: Dominant negative FADD dissipates the proapoptotic signalosome of the unfolded protein response in diabetic embryopathy. Am J Physiol Endocrinol Metab. 309(10):E861-73, 2015
                              11. Yang P et al: Decoding the oxidative stress hypothesis in diabetic embryopathy through proapoptotic kinase signaling. Am J Obstet Gynecol. 212(5):569-79, 2015
                              12. Zhong J et al: Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects. Biochem Biophys Res Commun. 467(2):179-84, 2015
                              13. El Hajj N et al: Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment. Reproduction. 148(6):R111-20, 2014
                              14. Moreli JB et al: DNA damage and its cellular response in mother and fetus exposed to hyperglycemic environment. Biomed Res Int. 2014:676758, 2014
                              15. Persson M et al: Perinatal outcome in relation to fetal sex in offspring to mothers with pre-gestational and gestational diabetes--a population-based study. Diabet Med. 31(9):1047-54, 2014
                              16. Wei D et al: Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy. Diabetes. 63(10):3512-22, 2014
                              17. Zhao Z: TGFβ and Wnt in cardiac outflow tract defects in offspring of diabetic pregnancies. Birth Defects Res B Dev Reprod Toxicol. 101(5):364-70, 2014
                              18. Castori M: Diabetic embryopathy: a developmental perspective from fertilization to adulthood. Mol Syndromol. 4(1-2):74-86, 2013
                              19. Heerwagen MJ et al: Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 299(3):R711-22, 2010
                              20. Lisowski LA et al: Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz. 35(1):19-26, 2010
                              21. Adam MP et al: Preaxial hallucal polydactyly as a marker for diabetic embryopathy. Birth Defects Res A Clin Mol Teratol. 85(1):13-9, 2009
                              22. Sugimura Y et al: Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes. Diabetologia. 52(5):962-71, 2009
                              Related Anatomy
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                              References
                              Tables

                              Tables

                              KEY FACTS

                              • Terminology

                                • Imaging

                                  • Pathology

                                    • Clinical Issues

                                      TERMINOLOGY

                                      • Definitions

                                        • Pregestational diabetes (type I or II): Diabetes mellitus diagnosis predates pregnancy
                                        • Gestational diabetes mellitus (GDM): Any degree of glucose intolerance initially diagnosed during pregnancy
                                          • Diagnosis by oral glucose tolerance test from 24-28 weeks gestation
                                          • GDM, by definition, resolves following pregnancy, although recurrence in subsequent pregnancies is common
                                            • Increased risk of developing type II diabetes (40-50% within 10 years)
                                          • Controversy exists regarding risk of anomalies in GDM
                                            • Anomalies in GDM may reflect undiagnosed type II diabetic

                                      IMAGING

                                      • General Features

                                        • Ultrasonographic Findings

                                          • Imaging Recommendations

                                            DIFFERENTIAL DIAGNOSIS

                                              PATHOLOGY

                                              • General Features

                                                • Staging, Grading, & Classification

                                                  • Microscopic Features

                                                    CLINICAL ISSUES

                                                    • Presentation

                                                      • Natural History & Prognosis

                                                        • Treatment

                                                          Selected References

                                                          1. Bohuslavova R et al: Gene expression profiling of changes induced by maternal diabetes in the embryonic heart. Reprod Toxicol. 57:147-56, 2015
                                                          2. Dong D et al: New development of the yolk sac theory in diabetic embryopathy: molecular mechanism and link to structural birth defects. Am J Obstet Gynecol. 214(2): 192-202, 2015
                                                          3. Dong D et al: Maternal diabetes triggers DNA damage and DNA damage response in neurulation stage embryos through oxidative stress. Biochem Biophys Res Commun. 467(2):407-12, 2015
                                                          4. Gabbay-Benziv R et al: Birth defects in pregestational diabetes: Defect range, glycemic threshold and pathogenesis. World J Diabetes. 6(3):481-8, 2015
                                                          5. López-Escobar B et al: The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye. Dis Model Mech. 8(2):157-68, 2015
                                                          6. Mitanchez D et al: The offspring of the diabetic mother--short- and long-term implications. Best Pract Res Clin Obstet Gynaecol. 29(2):256-69, 2015
                                                          7. Ornoy A et al: Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Res C Embryo Today. 105(1):53-72, 2015
                                                          8. Wang F et al: Advances in revealing the molecular targets downstream of oxidative stress-induced proapoptotic kinase signaling in diabetic embryopathy. Am J Obstet Gynecol. 213(2):125-34, 2015
                                                          9. Wang F et al: Oxidative stress is responsible for maternal diabetes-impaired transforming growth factor beta signaling in the developing mouse heart. Am J Obstet Gynecol. 212(5):650.e1-11, 2015
                                                          10. Wang F et al: Dominant negative FADD dissipates the proapoptotic signalosome of the unfolded protein response in diabetic embryopathy. Am J Physiol Endocrinol Metab. 309(10):E861-73, 2015
                                                          11. Yang P et al: Decoding the oxidative stress hypothesis in diabetic embryopathy through proapoptotic kinase signaling. Am J Obstet Gynecol. 212(5):569-79, 2015
                                                          12. Zhong J et al: Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects. Biochem Biophys Res Commun. 467(2):179-84, 2015
                                                          13. El Hajj N et al: Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment. Reproduction. 148(6):R111-20, 2014
                                                          14. Moreli JB et al: DNA damage and its cellular response in mother and fetus exposed to hyperglycemic environment. Biomed Res Int. 2014:676758, 2014
                                                          15. Persson M et al: Perinatal outcome in relation to fetal sex in offspring to mothers with pre-gestational and gestational diabetes--a population-based study. Diabet Med. 31(9):1047-54, 2014
                                                          16. Wei D et al: Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy. Diabetes. 63(10):3512-22, 2014
                                                          17. Zhao Z: TGFβ and Wnt in cardiac outflow tract defects in offspring of diabetic pregnancies. Birth Defects Res B Dev Reprod Toxicol. 101(5):364-70, 2014
                                                          18. Castori M: Diabetic embryopathy: a developmental perspective from fertilization to adulthood. Mol Syndromol. 4(1-2):74-86, 2013
                                                          19. Heerwagen MJ et al: Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 299(3):R711-22, 2010
                                                          20. Lisowski LA et al: Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz. 35(1):19-26, 2010
                                                          21. Adam MP et al: Preaxial hallucal polydactyly as a marker for diabetic embryopathy. Birth Defects Res A Clin Mol Teratol. 85(1):13-9, 2009
                                                          22. Sugimura Y et al: Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes. Diabetologia. 52(5):962-71, 2009