Maternal Adipose Tissue and Placental Dysfunction Programs the Fetus for Type 2 Diabetes (PlacentA-DM) (PlacentA-DM)
24 de abril de 2018 actualizado por: AdventHealth Translational Research Institute
The purpose of this study is to discover the characteristics of pregnant women which increases risk for their babies to develop diabetes, later on in life.
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
Obesity has been recently diagnosed in a younger population and currently in the United States more than two thirds of women of childbearing age are overweight or obese. These women will have children at high risk for developing obesity and Type 2 diabetes (T2DM). There is an acute need for preventing these complications in children so that we can break the cycle of obesity and T2DM. Numerous interventions have attempted but failed to improve outcomes in obese pregnancies by weight loss. Clinicians do not currently have specific recommendation for identifying the obese mothers and risk and for the prevention of infant's complication in healthy obese pregnancies.
The global objective of this study is to identify the relevant maternal phenotype at risk and the mechanism(s) of fetal environment predisposing the offspring for T2DM. This will enhance T2DM early screening and prevention.
The global hypothesis is that dysfunctional adipose tissue secretes angiostatic and pro-inflammatory factors that lead to the formation of a dysfunctional placenta, which through a hypoxic and inflamed environment alters the epigenome to program the fetus for T2DM.
Tipo de estudio
De observación
Inscripción (Actual)
3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Florida
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Orlando, Florida, Estados Unidos, 32804
- Translational Research Institute for Metabolism and Diabetes
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 40 años (Adulto)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Femenino
Método de muestreo
Muestra no probabilística
Población de estudio
Vulnerable populations- Pregnant Women, Fetuses and Neonates
Propose to study pregnant women in order to determine the relevant phenotype with offspring at risk for obesity and T2DM.
Descripción
Pregnant women Inclusion Criteria:
- Pregnant women undergoing planned cesarean section at 39 weeks of gestation due to: a) elective cesarean section; b) breach presentation c) repeat cesarean section (the rationale for choosing these women is to select only women that have no other risk factors or complications during pregnancy that might affect the outcome)
- Age between 18 and 40 years old
- Pre-pregnancy BMI between 20 and 25 kg/m2 (lean) and >30 kg/m2 (obese)
- Singleton pregnancies
- Allowing their neonates to participate in the trial
Pregnant women Exclusion Criteria:
- Taking any medication except pre-natal vitamins and medication to treat normal symptoms of pregnancy like: constipation, nausea, vomiting, gastric reflux, insomnia and pain.
- Type 1 diabetes, type 2 diabetes or gestational diabetes; chronic or gestational hypertension
- Pre-eclampsia, eclampsia during this pregnancy
- Liver, kidney, thyroid disease, cancer
- Smoking or using illegal drugs or alcohol during this pregnancy
- Fetal umbilical blood and/or placenta are collected for another reason, i.e. parents decide on cord blood storage
Neonate Inclusion criteria:
- Live neonates born to the study participating mothers
Neonate exclusion criteria:
- Neonate distress as to require admission to the Neonatal Intensive Care Unit.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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ObeseDYS
Obese subjects with dysfunctional vascularization and inflammation of placenta.
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ObeseNL
Obese subjects with normal vascularization and inflammation of placenta
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LeanNL
Lean subjects with normal vascularization and inflammation of placenta.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Quantity of Blood Vessels and Capillaries
Periodo de tiempo: Visit 3, at 39 weeks
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Measurements will be immunohistochemistry and measured from placental tissue.
Neonate's anthropometrics and sex will be recorded within 48 hours of the delivery by the Pediatrician and will last approximately 15 minutes.
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Visit 3, at 39 weeks
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Quantity of macrophages
Periodo de tiempo: Visit 3 at 39 weeks + 1 day
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Measured by immunohistochemistry, flow cytometry (FACS) of placental tissue
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Visit 3 at 39 weeks + 1 day
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Steven R Smith, MD, Translational Research Institute for Metabolism and Diabetes
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Vucetic Z, Kimmel J, Reyes TM. Chronic high-fat diet drives postnatal epigenetic regulation of mu-opioid receptor in the brain. Neuropsychopharmacology. 2011 May;36(6):1199-206. doi: 10.1038/npp.2011.4. Epub 2011 Feb 16.
- Catalano PM, Farrell K, Thomas A, Huston-Presley L, Mencin P, de Mouzon SH, Amini SB. Perinatal risk factors for childhood obesity and metabolic dysregulation. Am J Clin Nutr. 2009 Nov;90(5):1303-13. doi: 10.3945/ajcn.2008.27416. Epub 2009 Sep 16.
- Catalano PM, Presley L, Minium J, Hauguel-de Mouzon S. Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care. 2009 Jun;32(6):1076-80. doi: 10.2337/dc08-2077.
- Ling C, Groop L. Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes. 2009 Dec;58(12):2718-25. doi: 10.2337/db09-1003. No abstract available.
- Aagaard-Tillery KM, Grove K, Bishop J, Ke X, Fu Q, McKnight R, Lane RH. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol. 2008 Aug;41(2):91-102. doi: 10.1677/JME-08-0025. Epub 2008 May 30.
- Dabelea D, Crume T. Maternal environment and the transgenerational cycle of obesity and diabetes. Diabetes. 2011 Jul;60(7):1849-55. doi: 10.2337/db11-0400. No abstract available.
- Sullivan EL, Smith MS, Grove KL. Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology. 2011;93(1):1-8. doi: 10.1159/000322038. Epub 2010 Nov 13.
- Crume TL, Ogden L, Daniels S, Hamman RF, Norris JM, Dabelea D. The impact of in utero exposure to diabetes on childhood body mass index growth trajectories: the EPOCH study. J Pediatr. 2011 Jun;158(6):941-6. doi: 10.1016/j.jpeds.2010.12.007. Epub 2011 Jan 15.
- Dabelea D, Mayer-Davis EJ, Lamichhane AP, D'Agostino RB Jr, Liese AD, Vehik KS, Narayan KM, Zeitler P, Hamman RF. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study. Diabetes Care. 2008 Jul;31(7):1422-6. doi: 10.2337/dc07-2417. Epub 2008 Mar 28.
- Mingrone G, Manco M, Mora ME, Guidone C, Iaconelli A, Gniuli D, Leccesi L, Chiellini C, Ghirlanda G. Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care. 2008 Sep;31(9):1872-6. doi: 10.2337/dc08-0432. Epub 2008 Jun 5.
- Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EH, Piersma AH, Ozanne SE, Twinn DF, Remacle C, Rowlerson A, Poston L, Taylor PD. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008 Feb;51(2):383-92. doi: 10.1161/HYPERTENSIONAHA.107.101477. Epub 2007 Dec 17.
- Bayol SA, Simbi BH, Bertrand JA, Stickland NC. Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol. 2008 Jul 1;586(13):3219-30. doi: 10.1113/jphysiol.2008.153817. Epub 2008 May 8.
- Muhlhausler BS, Duffield JA, McMillen IC. Increased maternal nutrition stimulates peroxisome proliferator activated receptor-gamma, adiponectin, and leptin messenger ribonucleic acid expression in adipose tissue before birth. Endocrinology. 2007 Feb;148(2):878-85. doi: 10.1210/en.2006-1115. Epub 2006 Oct 26.
- Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF. Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci. 2008 Nov 12;28(46):12107-19. doi: 10.1523/JNEUROSCI.2642-08.2008.
- Walker CD, Naef L, d'Asti E, Long H, Xu Z, Moreau A, Azeddine B. Perinatal maternal fat intake affects metabolism and hippocampal function in the offspring: a potential role for leptin. Ann N Y Acad Sci. 2008 Nov;1144:189-202. doi: 10.1196/annals.1418.023.
- Shankar K, Kang P, Harrell A, Zhong Y, Marecki JC, Ronis MJ, Badger TM. Maternal overweight programs insulin and adiponectin signaling in the offspring. Endocrinology. 2010 Jun;151(6):2577-89. doi: 10.1210/en.2010-0017. Epub 2010 Apr 6.
- Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature. 2010 Oct 21;467(7318):963-6. doi: 10.1038/nature09491.
- Suter MA, Chen A, Burdine MS, Choudhury M, Harris RA, Lane RH, Friedman JE, Grove KL, Tackett AJ, Aagaard KM. A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates. FASEB J. 2012 Dec;26(12):5106-14. doi: 10.1096/fj.12-212878. Epub 2012 Sep 14.
- Sohi G, Marchand K, Revesz A, Arany E, Hardy DB. Maternal protein restriction elevates cholesterol in adult rat offspring due to repressive changes in histone modifications at the cholesterol 7alpha-hydroxylase promoter. Mol Endocrinol. 2011 May;25(5):785-98. doi: 10.1210/me.2010-0395. Epub 2011 Mar 3.
- Gong L, Pan YX, Chen H. Gestational low protein diet in the rat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation. Epigenetics. 2010 Oct 1;5(7):619-26. doi: 10.4161/epi.5.7.12882. Epub 2010 Oct 1.
- van Straten EM, Bloks VW, Huijkman NC, Baller JF, van Meer H, Lutjohann D, Kuipers F, Plosch T. The liver X-receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction. Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R275-82. doi: 10.1152/ajpregu.00413.2009. Epub 2009 Nov 4.
- Zheng S, Rollet M, Pan YX. Maternal protein restriction during pregnancy induces CCAAT/enhancer-binding protein (C/EBPbeta) expression through the regulation of histone modification at its promoter region in female offspring rat skeletal muscle. Epigenetics. 2011 Feb;6(2):161-70. doi: 10.4161/epi.6.2.13472. Epub 2011 Feb 1.
- Zhou D, Pan YX. Gestational low protein diet selectively induces the amino acid response pathway target genes in the liver of offspring rats through transcription factor binding and histone modifications. Biochim Biophys Acta. 2011 Oct;1809(10):549-56. doi: 10.1016/j.bbagrm.2011.07.003. Epub 2011 Jul 18.
- Jousse C, Parry L, Lambert-Langlais S, Maurin AC, Averous J, Bruhat A, Carraro V, Tost J, Letteron P, Chen P, Jockers R, Launay JM, Mallet J, Fafournoux P. Perinatal undernutrition affects the methylation and expression of the leptin gene in adults: implication for the understanding of metabolic syndrome. FASEB J. 2011 Sep;25(9):3271-8. doi: 10.1096/fj.11-181792. Epub 2011 Jun 13.
- Zhang S, Rattanatray L, MacLaughlin SM, Cropley JE, Suter CM, Molloy L, Kleemann D, Walker SK, Muhlhausler BS, Morrison JL, McMillen IC. Periconceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring. FASEB J. 2010 Aug;24(8):2772-82. doi: 10.1096/fj.09-154294. Epub 2010 Apr 6.
- Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar SU. Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem. 2008 May 16;283(20):13611-26. doi: 10.1074/jbc.M800128200. Epub 2008 Mar 7.
- Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA, Greally JM. Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats. J Biol Chem. 2010 May 14;285(20):15111-15118. doi: 10.1074/jbc.M109.095133. Epub 2010 Mar 1.
- Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009 Nov 1;18(21):4046-53. doi: 10.1093/hmg/ddp353. Epub 2009 Aug 4.
- Durmus B, Arends LR, Ay L, Hokken-Koelega AC, Raat H, Hofman A, Steegers EA, Jaddoe VW. Parental anthropometrics, early growth and the risk of overweight in pre-school children: the Generation R Study. Pediatr Obes. 2013 Oct;8(5):339-50. doi: 10.1111/j.2047-6310.2012.00114.x. Epub 2012 Dec 13.
- Drong AW, Lindgren CM, McCarthy MI. The genetic and epigenetic basis of type 2 diabetes and obesity. Clin Pharmacol Ther. 2012 Dec;92(6):707-15. doi: 10.1038/clpt.2012.149. Epub 2012 Oct 10.
- Toperoff G, Aran D, Kark JD, Rosenberg M, Dubnikov T, Nissan B, Wainstein J, Friedlander Y, Levy-Lahad E, Glaser B, Hellman A. Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet. 2012 Jan 15;21(2):371-83. doi: 10.1093/hmg/ddr472. Epub 2011 Oct 12.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de diciembre de 2013
Finalización primaria (Actual)
1 de diciembre de 2016
Finalización del estudio (Actual)
1 de enero de 2017
Fechas de registro del estudio
Enviado por primera vez
16 de mayo de 2014
Primero enviado que cumplió con los criterios de control de calidad
6 de agosto de 2014
Publicado por primera vez (Estimar)
7 de agosto de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
25 de abril de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
24 de abril de 2018
Última verificación
1 de abril de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- TRIMDFH 499458
- 499458 (Otro identificador: Florida Hospital IRB)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .