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Erschienen in: Current Diabetes Reports 1/2012

01.02.2012 | Diabetes and Pregnancy (CJ Homko, Section Editor)

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

verfasst von: E. Albert Reece

Erschienen in: Current Diabetes Reports | Ausgabe 1/2012

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Abstract

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.
Literatur
2.
Zurück zum Zitat Heron M, Tejada-Vera B. Deaths: leading causes for 2005. Natl Vital Stat Rep. 2009;58(8):1–97.PubMed Heron M, Tejada-Vera B. Deaths: leading causes for 2005. Natl Vital Stat Rep. 2009;58(8):1–97.PubMed
5.
Zurück zum Zitat Fetita LS, Sobngwi E, Serradas P, et al. Consequences of fetal exposure to maternal diabetes in offspring. J Clin Endocrinol Metab. 2006;91:3718–24.PubMedCrossRef Fetita LS, Sobngwi E, Serradas P, et al. Consequences of fetal exposure to maternal diabetes in offspring. J Clin Endocrinol Metab. 2006;91:3718–24.PubMedCrossRef
6.
Zurück zum Zitat Potenza MA, Nacci C, Gagliardi S, Montagnani M. Cardiovascular complications in diabetes: lessons from animal models. Curr Med Chem. 2011;18:1806–19.PubMedCrossRef Potenza MA, Nacci C, Gagliardi S, Montagnani M. Cardiovascular complications in diabetes: lessons from animal models. Curr Med Chem. 2011;18:1806–19.PubMedCrossRef
7.
Zurück zum Zitat Eidem I, Stene LC, Henriksen T, et al. Congenital anomalies in newborns of women with type 1 diabetes: nationwide population-based study in Norway, 1999–2004. Acta Obstet Gynecol Scand. 2010;89:1403–11.PubMedCrossRef Eidem I, Stene LC, Henriksen T, et al. Congenital anomalies in newborns of women with type 1 diabetes: nationwide population-based study in Norway, 1999–2004. Acta Obstet Gynecol Scand. 2010;89:1403–11.PubMedCrossRef
8.
Zurück zum Zitat Biggio Jr JR, Chapman V, Neely C, et al. Fetal anomalies in obese women: the contribution of diabetes. Obstet Gynecol. 2010;115:290–6.PubMedCrossRef Biggio Jr JR, Chapman V, Neely C, et al. Fetal anomalies in obese women: the contribution of diabetes. Obstet Gynecol. 2010;115:290–6.PubMedCrossRef
9.
Zurück zum Zitat Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol. 2008;199:237.e1–9.CrossRef Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol. 2008;199:237.e1–9.CrossRef
10.
Zurück zum Zitat Reece EA, Homko CJ, Wu YK. Multifactorial basis of the syndrome of diabetic embryopathy. Teratology. 1996;54:171–82.PubMedCrossRef Reece EA, Homko CJ, Wu YK. Multifactorial basis of the syndrome of diabetic embryopathy. Teratology. 1996;54:171–82.PubMedCrossRef
11.
Zurück zum Zitat Reece EA, Pinter E, Homko C, et al. The yolk sac theory: closing the circle on why diabetes-associated malformations occur. J Soc Gynecol Investig. 1994;1:3–13.PubMed Reece EA, Pinter E, Homko C, et al. The yolk sac theory: closing the circle on why diabetes-associated malformations occur. J Soc Gynecol Investig. 1994;1:3–13.PubMed
12.
Zurück zum Zitat Mironiuk M, Kietlińska Z, Jezierska-Kasprzyk K, Piekosz-Orzechowska B. A class of diabetes in mother, glycemic control in early pregnancy and occurrence of congenital malformations in newborn infants. Clin Exp Obstet Gynecol. 1997;24:193–7.PubMed Mironiuk M, Kietlińska Z, Jezierska-Kasprzyk K, Piekosz-Orzechowska B. A class of diabetes in mother, glycemic control in early pregnancy and occurrence of congenital malformations in newborn infants. Clin Exp Obstet Gynecol. 1997;24:193–7.PubMed
13.
Zurück zum Zitat Reece EA, Gabrielli S, Abdalla M. The prevention of diabetes-associated birth defects. Semin Perinatol. 1988;12:292–301.PubMed Reece EA, Gabrielli S, Abdalla M. The prevention of diabetes-associated birth defects. Semin Perinatol. 1988;12:292–301.PubMed
14.
Zurück zum Zitat Hone J, Jovanovic L. Approach to the patient with diabetes during pregnancy. J Clin Endocrinol Metab. 2010;95:3578–85.PubMedCrossRef Hone J, Jovanovic L. Approach to the patient with diabetes during pregnancy. J Clin Endocrinol Metab. 2010;95:3578–85.PubMedCrossRef
15.
Zurück zum Zitat Homko CJ, Khandelwal M. Glucose monitoring and insulin therapy during pregnancy. Obstet Gynecol Clin North Am. 1996;23:47–74.PubMedCrossRef Homko CJ, Khandelwal M. Glucose monitoring and insulin therapy during pregnancy. Obstet Gynecol Clin North Am. 1996;23:47–74.PubMedCrossRef
16.
Zurück zum Zitat Reece EA, Homko CJ. Diabetes mellitus in pregnancy. What are the best treatment options? Drug Saf. 1998;18:209–20.PubMedCrossRef Reece EA, Homko CJ. Diabetes mellitus in pregnancy. What are the best treatment options? Drug Saf. 1998;18:209–20.PubMedCrossRef
17.
Zurück zum Zitat Kitzmiller JL, Gavin LA, Gin GD, et al. Preconception care of diabetes. Glycemic control prevents congenital anomalies. JAMA. 1991;265:731–6.PubMedCrossRef Kitzmiller JL, Gavin LA, Gin GD, et al. Preconception care of diabetes. Glycemic control prevents congenital anomalies. JAMA. 1991;265:731–6.PubMedCrossRef
18.
Zurück zum Zitat Fuhrmann K, Reiher H, Semmler K, Glöckner E. The effect of intensified conventional insulin therapy before and during pregnancy on the malformation rate in offspring of diabetic mothers. Exp Clin Endocrinol. 1984;83:173–7.PubMedCrossRef Fuhrmann K, Reiher H, Semmler K, Glöckner E. The effect of intensified conventional insulin therapy before and during pregnancy on the malformation rate in offspring of diabetic mothers. Exp Clin Endocrinol. 1984;83:173–7.PubMedCrossRef
19.
Zurück zum Zitat Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health. 2006;38:90–6.PubMedCrossRef Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health. 2006;38:90–6.PubMedCrossRef
20.
Zurück zum Zitat HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991–2002.PubMedCrossRef HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991–2002.PubMedCrossRef
21.
Zurück zum Zitat Dalewitz J, Khan N, Hershey CO. Barriers to control of blood glucose in diabetes mellitus. Am J Med Qual. 2000;15:16–25.PubMedCrossRef Dalewitz J, Khan N, Hershey CO. Barriers to control of blood glucose in diabetes mellitus. Am J Med Qual. 2000;15:16–25.PubMedCrossRef
22.
Zurück zum Zitat Hay LC, Wilmshurst EG, Fulcher G. Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the results of continuous glucose monitoring. Diabetes Technol Ther. 2003;5:19–26.PubMedCrossRef Hay LC, Wilmshurst EG, Fulcher G. Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the results of continuous glucose monitoring. Diabetes Technol Ther. 2003;5:19–26.PubMedCrossRef
23.
Zurück zum Zitat Vaddiraju S, Burgess DJ, Tomazos I, et al. Technologies for continuous glucose monitoring: current problems and future promises. J Diabetes Sci Technol. 2010;4:1540–62.PubMed Vaddiraju S, Burgess DJ, Tomazos I, et al. Technologies for continuous glucose monitoring: current problems and future promises. J Diabetes Sci Technol. 2010;4:1540–62.PubMed
24.
Zurück zum Zitat Wilson RD, Johnson JA, Wyatt P, et al. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can. 2007;29:1003–26.PubMed Wilson RD, Johnson JA, Wyatt P, et al. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can. 2007;29:1003–26.PubMed
25.
Zurück zum Zitat Bánhidy F, Dakhlaoui A, Puhó EH, Czeizel AA. Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population-based case–control study. Congenit Anom (Kyoto). 2011;51:80–6.CrossRef Bánhidy F, Dakhlaoui A, Puhó EH, Czeizel AA. Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population-based case–control study. Congenit Anom (Kyoto). 2011;51:80–6.CrossRef
26.
Zurück zum Zitat Correa A, Botto L, Liu Y, Mulinare J, Erickson JD. Do multivitamin supplements attenuate the risk for diabetes-associated birth defects? Pediatrics. 2003;111:1146–51.PubMed Correa A, Botto L, Liu Y, Mulinare J, Erickson JD. Do multivitamin supplements attenuate the risk for diabetes-associated birth defects? Pediatrics. 2003;111:1146–51.PubMed
27.
Zurück zum Zitat Wallach JB, Rey MJ. A socioeconomic analysis of obesity and diabetes in New York City. Prev Chronic Dis. 2009;6:A108.PubMed Wallach JB, Rey MJ. A socioeconomic analysis of obesity and diabetes in New York City. Prev Chronic Dis. 2009;6:A108.PubMed
28.
Zurück zum Zitat Waller K. Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med. 2007;161:745–50.PubMedCrossRef Waller K. Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med. 2007;161:745–50.PubMedCrossRef
29.
Zurück zum Zitat Carmichael SL, Yang W, Feldkamp ML, et al. Reduced risks of neural tube defects and orofacial clefts with higher diet quality. Arch Pediatr Adolesc Med. 2011; Oct 3. [Epub ahead of print] Carmichael SL, Yang W, Feldkamp ML, et al. Reduced risks of neural tube defects and orofacial clefts with higher diet quality. Arch Pediatr Adolesc Med. 2011; Oct 3. [Epub ahead of print]
30.
Zurück zum Zitat Stotland NE, Gilbert P, Bogetz A, et al. Preventing excessive weight gain in pregnancy: how do prenatal care providers approach counseling? J Womens Health (Larchmt). 2010;19:807–14.CrossRef Stotland NE, Gilbert P, Bogetz A, et al. Preventing excessive weight gain in pregnancy: how do prenatal care providers approach counseling? J Womens Health (Larchmt). 2010;19:807–14.CrossRef
31.
Zurück zum Zitat Jay M, Gillespie C, Ark T, et al. Do internists, pediatricians, and psychiatrists feel competent in obesity care? Using a needs assessment to drive curriculum design. J Gen Intern Med. 2008;23:1066–70.PubMedCrossRef Jay M, Gillespie C, Ark T, et al. Do internists, pediatricians, and psychiatrists feel competent in obesity care? Using a needs assessment to drive curriculum design. J Gen Intern Med. 2008;23:1066–70.PubMedCrossRef
32.
Zurück zum Zitat Chang MW, Nitzke S, Guilford E, et al. Motivators and barriers to healthful eating and physical activity among low-income overweight and obese mothers. J Am Diet Assoc. 2008;108:1023–8.PubMedCrossRef Chang MW, Nitzke S, Guilford E, et al. Motivators and barriers to healthful eating and physical activity among low-income overweight and obese mothers. J Am Diet Assoc. 2008;108:1023–8.PubMedCrossRef
33.
Zurück zum Zitat Reece EA, Homko CJ. Prepregnancy care and the prevention of fetal malformations in the pregnancy complicated by diabetes. Clin Obstet Gynecol. 2007;50:990–7.PubMedCrossRef Reece EA, Homko CJ. Prepregnancy care and the prevention of fetal malformations in the pregnancy complicated by diabetes. Clin Obstet Gynecol. 2007;50:990–7.PubMedCrossRef
34.
Zurück zum Zitat Piomelli D. Arachidonic acid in cell signalling. Austin: Chapmam and Hall; 1996. Piomelli D. Arachidonic acid in cell signalling. Austin: Chapmam and Hall; 1996.
35.
Zurück zum Zitat Jawerbaum A, Gonzalez E. The role of alterations in arachidonic acid metabolism and nitric oxide homeostasis in rat models of diabetes during early pregnancy. Curr Pharm Des. 2005;11:1327–42.PubMedCrossRef Jawerbaum A, Gonzalez E. The role of alterations in arachidonic acid metabolism and nitric oxide homeostasis in rat models of diabetes during early pregnancy. Curr Pharm Des. 2005;11:1327–42.PubMedCrossRef
36.
Zurück zum Zitat Wiznitzer A, Furman B, Mazor M, Reece EA. The role of prostanoids in the development of diabetic embryopathy. Semin Reprod Endocrinol. 1999;17:175–81.PubMedCrossRef Wiznitzer A, Furman B, Mazor M, Reece EA. The role of prostanoids in the development of diabetic embryopathy. Semin Reprod Endocrinol. 1999;17:175–81.PubMedCrossRef
37.
Zurück zum Zitat Chang HY, Locker J, Lu R, Schuster VL. Failure of postnatal ductus arteriosus closure in prostaglandin transporter-deficient mice. Circulation. 2010;121:529–36.PubMedCrossRef Chang HY, Locker J, Lu R, Schuster VL. Failure of postnatal ductus arteriosus closure in prostaglandin transporter-deficient mice. Circulation. 2010;121:529–36.PubMedCrossRef
38.
Zurück zum Zitat Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.PubMedCrossRef Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.PubMedCrossRef
39.
Zurück zum Zitat Kukuljan M, Vergara L, Stojilkovic SS. Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca2+]i oscillations by calcium entry in pituitary gonadotrophs. Biophys J. 1997;72:698–707.PubMedCrossRef Kukuljan M, Vergara L, Stojilkovic SS. Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca2+]i oscillations by calcium entry in pituitary gonadotrophs. Biophys J. 1997;72:698–707.PubMedCrossRef
40.
Zurück zum Zitat Larner J. D-chiro-inositol—its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3:47–60.PubMedCrossRef Larner J. D-chiro-inositol—its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3:47–60.PubMedCrossRef
41.
Zurück zum Zitat Gerasimenko JV, Flowerdew SE, Voronina SG, et al. Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. J Biol Chem. 2006;281:40154–63.PubMedCrossRef Gerasimenko JV, Flowerdew SE, Voronina SG, et al. Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. J Biol Chem. 2006;281:40154–63.PubMedCrossRef
42.
Zurück zum Zitat Rapiejko PJ, Northup JK, Evans T, et al. G-proteins of fat-cells. Role in hormonal regulation of intracellular inositol 1,4,5-trisphosphate. Biochem J. 1986;240:35–40.PubMed Rapiejko PJ, Northup JK, Evans T, et al. G-proteins of fat-cells. Role in hormonal regulation of intracellular inositol 1,4,5-trisphosphate. Biochem J. 1986;240:35–40.PubMed
43.
Zurück zum Zitat Shen X, Xiao H, Ranallo R, et al. Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science. 2003;299:112–4.PubMedCrossRef Shen X, Xiao H, Ranallo R, et al. Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science. 2003;299:112–4.PubMedCrossRef
44.
Zurück zum Zitat Steger DJ, Haswell ES, Miller AL, et al. Regulation of chromatin remodelling by inositol polyphosphates. Science. 2003;299:114–6.PubMedCrossRef Steger DJ, Haswell ES, Miller AL, et al. Regulation of chromatin remodelling by inositol polyphosphates. Science. 2003;299:114–6.PubMedCrossRef
45.
Zurück zum Zitat Pinter E, Reece EA, Leranth CZ, Garcia-Segura M, Hobbins JC, Mahoney MJ, et al. Arachidonic acid prevents hyperglycemia-associated yolk sac damage and embryopathy. Am J Obstet Gynecol. 1986;155:691–702.PubMed Pinter E, Reece EA, Leranth CZ, Garcia-Segura M, Hobbins JC, Mahoney MJ, et al. Arachidonic acid prevents hyperglycemia-associated yolk sac damage and embryopathy. Am J Obstet Gynecol. 1986;155:691–702.PubMed
46.
47.
Zurück zum Zitat James AM, Murphy MP. How mitochondrial damage affects cell function. J Biomed Sci. 2002;9:475–87.PubMedCrossRef James AM, Murphy MP. How mitochondrial damage affects cell function. J Biomed Sci. 2002;9:475–87.PubMedCrossRef
48.
Zurück zum Zitat Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000;404:787–90.PubMedCrossRef Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000;404:787–90.PubMedCrossRef
49.
Zurück zum Zitat Hagay ZJ, Weiss Y, Zusman I, et al. Prevention of diabetes-associated embryopathy by overexpression of the free radical scavenger copper zinc superoxide dismutase in transgenic mouse embryos. AJOG. 1995;173:1036–41.CrossRef Hagay ZJ, Weiss Y, Zusman I, et al. Prevention of diabetes-associated embryopathy by overexpression of the free radical scavenger copper zinc superoxide dismutase in transgenic mouse embryos. AJOG. 1995;173:1036–41.CrossRef
50.
Zurück zum Zitat Mao LM, Liu XY, Zhang GC, et al. Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo. Neuropharmacology. 2008;55:403–8.PubMedCrossRef Mao LM, Liu XY, Zhang GC, et al. Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo. Neuropharmacology. 2008;55:403–8.PubMedCrossRef
51.
Zurück zum Zitat Steinberg SF. Distinctive activation mechanisms and functions for protein kinase Cdelta. Biochem J. 2004;384:449–59.PubMedCrossRef Steinberg SF. Distinctive activation mechanisms and functions for protein kinase Cdelta. Biochem J. 2004;384:449–59.PubMedCrossRef
52.
Zurück zum Zitat Dempsey EC, Newton AC, Mochly-Rosen D, et al. Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol Lung Cell Mol Physiol. 2000;279:L429–38.PubMed Dempsey EC, Newton AC, Mochly-Rosen D, et al. Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol Lung Cell Mol Physiol. 2000;279:L429–38.PubMed
53.
Zurück zum Zitat Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153–83.PubMedCrossRef Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153–83.PubMedCrossRef
54.
Zurück zum Zitat Alnemri ES, Livingston DJ, Nicholson DW, et al. Human ICE/CED-3 protease nomenclature. Cell. 1996;87:171.PubMedCrossRef Alnemri ES, Livingston DJ, Nicholson DW, et al. Human ICE/CED-3 protease nomenclature. Cell. 1996;87:171.PubMedCrossRef
55.
Zurück zum Zitat Fuentes-Prior P, Salvesen GS. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J. 2004;384:201–32.PubMedCrossRef Fuentes-Prior P, Salvesen GS. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J. 2004;384:201–32.PubMedCrossRef
56.
Zurück zum Zitat Koenen TB, Stienstra R, van Tits LJ, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue. Diabetes. 2011;60:517–24.PubMedCrossRef Koenen TB, Stienstra R, van Tits LJ, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue. Diabetes. 2011;60:517–24.PubMedCrossRef
57.
Zurück zum Zitat Kuan CY, Yang DD, Samanta Roy DR, et al. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron. 1999;22:667–76.PubMedCrossRef Kuan CY, Yang DD, Samanta Roy DR, et al. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron. 1999;22:667–76.PubMedCrossRef
58.
Zurück zum Zitat • Zhao Z, Yang P, Eckert RL, Reece EA. Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res B DevReprodToxicol. 2009;86:72–7. This study has had an important impact because it was the first to confirm the role of caspase-8 in diabetic embryopathy.CrossRef • Zhao Z, Yang P, Eckert RL, Reece EA. Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res B DevReprodToxicol. 2009;86:72–7. This study has had an important impact because it was the first to confirm the role of caspase-8 in diabetic embryopathy.CrossRef
59.
Zurück zum Zitat Yang P, Zhao Z, Reece EA. Involvement of c-Jun N-terminal kinases activation in diabetic embryopathy. Biochem Biophys Res Commun. 2007;357:749–54.PubMedCrossRef Yang P, Zhao Z, Reece EA. Involvement of c-Jun N-terminal kinases activation in diabetic embryopathy. Biochem Biophys Res Commun. 2007;357:749–54.PubMedCrossRef
60.
Zurück zum Zitat • Zhao Z, Yang P, Eckert RL, Reece EA. Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res B Dev Reprod Toxicol. 2009;86:72–7. This article has had a significant impact because it was the first to confirm the role of caspase-8 in the pathophysiology of diabetic embryopathy.PubMedCrossRef • Zhao Z, Yang P, Eckert RL, Reece EA. Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res B Dev Reprod Toxicol. 2009;86:72–7. This article has had a significant impact because it was the first to confirm the role of caspase-8 in the pathophysiology of diabetic embryopathy.PubMedCrossRef
61.
Zurück zum Zitat Reece EA, Wu YK. Prevention of diabetic embryopathy in offspring of diabetic rats with use of a cocktail of deficient substrates and an antioxidant. Am J Obstet Gynecol. 1997;176:790–7.PubMedCrossRef Reece EA, Wu YK. Prevention of diabetic embryopathy in offspring of diabetic rats with use of a cocktail of deficient substrates and an antioxidant. Am J Obstet Gynecol. 1997;176:790–7.PubMedCrossRef
62.
Zurück zum Zitat Kappen C, Kruger C, MacGowan J, Salbaum JM. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy. Reprod Toxicol. 2011;31:41–9.PubMedCrossRef Kappen C, Kruger C, MacGowan J, Salbaum JM. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy. Reprod Toxicol. 2011;31:41–9.PubMedCrossRef
63.
Zurück zum Zitat Pinter E, Reece EA, Leranth CZ, et al. Yolk sac failure in embryopathy due to hyperglycemia: ultrastructural analysis of yolk sac differentiation associated with embryopathy in rat conceptuses under hyperglycemic conditions. Teratology. 1986;33:73–84.PubMedCrossRef Pinter E, Reece EA, Leranth CZ, et al. Yolk sac failure in embryopathy due to hyperglycemia: ultrastructural analysis of yolk sac differentiation associated with embryopathy in rat conceptuses under hyperglycemic conditions. Teratology. 1986;33:73–84.PubMedCrossRef
64.
Zurück zum Zitat Reece EA, Wu YK, Wiznitzer A, et al. Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats. Am J Obstet Gynecol. 1996;175:818–23.PubMedCrossRef Reece EA, Wu YK, Wiznitzer A, et al. Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats. Am J Obstet Gynecol. 1996;175:818–23.PubMedCrossRef
65.
Zurück zum Zitat Reece EA, Wu YK, Zhao Z, Dhanasekaran D. Dietary vitamin and lipid therapy rescues aberrant signaling and apoptosis and prevents hyperglycemia-induced diabetic embryopathy in rats. Am J Obstet Gynecol. 2006;194:580–5.PubMedCrossRef Reece EA, Wu YK, Zhao Z, Dhanasekaran D. Dietary vitamin and lipid therapy rescues aberrant signaling and apoptosis and prevents hyperglycemia-induced diabetic embryopathy in rats. Am J Obstet Gynecol. 2006;194:580–5.PubMedCrossRef
66.
Zurück zum Zitat Khandelwal M, Reece EA, Wu YK, Borenstein M. Dietary myo-inositol therapy in hyperglycemia-induced embryopathy. Teratology. 1998;57:79–84.PubMedCrossRef Khandelwal M, Reece EA, Wu YK, Borenstein M. Dietary myo-inositol therapy in hyperglycemia-induced embryopathy. Teratology. 1998;57:79–84.PubMedCrossRef
67.
Zurück zum Zitat Wentzel P, Thunberg L, Eriksson UJ. Teratogenic effect of diabetic serum is prevented by supplementation of superoxide dismutase and N-acetylcysteine in rat embryo culture. Diabetologia. 1997;40:7–14.PubMedCrossRef Wentzel P, Thunberg L, Eriksson UJ. Teratogenic effect of diabetic serum is prevented by supplementation of superoxide dismutase and N-acetylcysteine in rat embryo culture. Diabetologia. 1997;40:7–14.PubMedCrossRef
68.
Zurück zum Zitat • Li X, Weng H, Reece EA, Yang P. SOD1 overexpression in vivo blocks hyperglycemia-induced specific PKC isoforms: substrate activation and consequent lipid peroxidation in diabetic embryopathy. Am J Obstet Gynecol. 2011 Mar 5;[Epub ahead of print]. This article has had a significant impact because it not only confirmed the role of the PKC pathway in diabetic embryopathy, but it also demonstrated that this pre-apoptotic cascade could be blocked and is a modifiable drug target. • Li X, Weng H, Reece EA, Yang P. SOD1 overexpression in vivo blocks hyperglycemia-induced specific PKC isoforms: substrate activation and consequent lipid peroxidation in diabetic embryopathy. Am J Obstet Gynecol. 2011 Mar 5;[Epub ahead of print]. This article has had a significant impact because it not only confirmed the role of the PKC pathway in diabetic embryopathy, but it also demonstrated that this pre-apoptotic cascade could be blocked and is a modifiable drug target.
69.
Zurück zum Zitat •• Cao Y, Zhao Z, Eckert RL, Reece EA. Protein kinase Cβ2 inhibition reduces hyperglycemia-induced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway. Am J Obstet Gynecol. 2011;204:226.e1–5. This paper demonstrated that not only can we reduce the risk of hyperglycemia-induced NTDs by inhibition of a specific PKC isoform, PKCβ2, but also that the mode of action is via suppression of the cellular apoptotic pathway. It further confirms that our approach to preventing diabetic embryopathies is justified and that there are multiple points in the pathophysiology of this disease that are potential therapeutic targets.CrossRef •• Cao Y, Zhao Z, Eckert RL, Reece EA. Protein kinase Cβ2 inhibition reduces hyperglycemia-induced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway. Am J Obstet Gynecol. 2011;204:226.e1–5. This paper demonstrated that not only can we reduce the risk of hyperglycemia-induced NTDs by inhibition of a specific PKC isoform, PKCβ2, but also that the mode of action is via suppression of the cellular apoptotic pathway. It further confirms that our approach to preventing diabetic embryopathies is justified and that there are multiple points in the pathophysiology of this disease that are potential therapeutic targets.CrossRef
70.
Zurück zum Zitat Rothenberg SP. Increasing the dietary intake of folate: pros and cons. Semin Hematol. 1999;36:65–74.PubMed Rothenberg SP. Increasing the dietary intake of folate: pros and cons. Semin Hematol. 1999;36:65–74.PubMed
71.
Zurück zum Zitat Tessema J, Jefferds ME, Cogswell M, Carlton E. Motivators and barriers to prenatal supplement use among minority women in the United States. J Am Diet Assoc. 2009;109:102–8.PubMedCrossRef Tessema J, Jefferds ME, Cogswell M, Carlton E. Motivators and barriers to prenatal supplement use among minority women in the United States. J Am Diet Assoc. 2009;109:102–8.PubMedCrossRef
72.
Zurück zum Zitat Reece EA. New developments in the prevention of diabetes-induced neural tube defects. Prenat Neonatal Med. 1996;1:97–9. Reece EA. New developments in the prevention of diabetes-induced neural tube defects. Prenat Neonatal Med. 1996;1:97–9.
Metadaten
Titel
Diabetes-Induced Birth Defects: What Do We Know? What Can We Do?
verfasst von
E. Albert Reece
Publikationsdatum
01.02.2012
Verlag
Current Science Inc.
Erschienen in
Current Diabetes Reports / Ausgabe 1/2012
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-011-0251-6

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