Maternal Adipose Tissue and Placental Dysfunction Programs the Fetus for Type 2 Diabetes (PlacentA-DM)

Obesity Clinical Trial

— PlacentA-DM  

Official title:

Maternal Adipose Tissue and Placental Dysfunction Programs the Fetus for Type 2 Diabetes (PlacentA-DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02211651
• Other study ID #: TRIMDFH 499458
• Secondary ID: 499458
• Status: Completed
• First received: May 16, 2014
• Last updated: April 24, 2018
• Start date: December 2013
• Est. completion date: January 2017

Study information

• Verified date: April 2018
• Source: Translational Research Institute for Metabolism and Diabetes, Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: January 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity
• Type 2 Diabetes

Locations

Country	Name	City	State
United States	Translational Research Institute for Metabolism and Diabetes	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Translational Research Institute for Metabolism and Diabetes, Florida	Sanford-Burnham Medical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (31)

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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. — View Citation

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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. — View Citation

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. Epub 2006 Oct 26. — View Citation

Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ. Chronic high-fat diet in fathers programs ß-cell dysfunction in female rat offspring. Nature. 2010 Oct 21;467(7318):963-6. doi: 10.1038/nature09491. — View Citation

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. — View Citation

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. Epub 2007 Dec 17. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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):15111-8. doi: 10.1074/jbc.M109.095133. Epub 2010 Mar 1. — View Citation

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van Straten EM, Bloks VW, Huijkman NC, Baller JF, van Meer H, Lütjohann D, Kuipers F, Plösch 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. — View Citation

Vucetic Z, Kimmel J, Reyes TM. Chronic high-fat diet drives postnatal epigenetic regulation of µ-opioid receptor in the brain. Neuropsychopharmacology. 2011 May;36(6):1199-206. doi: 10.1038/npp.2011.4. Epub 2011 Feb 16. — View Citation

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. — View Citation

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. — View Citation

Zheng S, Rollet M, Pan YX. Maternal protein restriction during pregnancy induces CCAAT/enhancer-binding protein (C/EBPß) 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. — View Citation

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. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantity of Blood Vessels and Capillaries	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.	Visit 3, at 39 weeks
Primary	Quantity of macrophages	Measured by immunohistochemistry, flow cytometry (FACS) of placental tissue	Visit 3 at 39 weeks + 1 day

External Links

•   Florida Hospital Translational Research Institute for Metabolism and Diabetes