In this project, we seek to identify novel blood-based epigenomic biomarkers to be used in early childhood as biomarkers of natural history of prenatal exposure to gestational diabetes (GDM) and for profiling risks of obesity and cardiometabolic phenotypes among children born to GDM mothers. We will leverage the largest prospective collections worldwide of biospecimens, anthropometry and laboratory data from the Tianjin GDM longitudinal observational study (TGDM-O), Tianjin, China, which have been funded by the European Foundation for the Study of Diabetes (EFSD).
In Aim 1, we will identify in a longitudinal observational study blood methylomic profiles in early childhood that reflect antecedent GDM exposures.
In Aim 2, we will identify in a longitudinal observational study blood methylomic profiles in early childhood that predict future obesity and dysmetabolism risk trajectories. To ensure generalizability, in Aim 3, we will confirm our findings in three large independent cohorts in the US and Europe (i.e., Project Viva, Avon Longitudinal Study of Parents and Children [ALSPAC], and Born in Bradford). This is the first study to prospectively examine the effects of GDM on the child?s methylome and metabolic health, and determine the generalizability of our findings in three independent cohorts. If successful, our project will provide accurate tools to guide childhood interventions through early biomarkers of effect. These biomarkers could be eventually used to implement personalized measures among children and enhance strategies to obesity prevention. The proposed research will generate a model that could be extended to other prenatal risk factors, as well as to other conditions with their root causes in pregnancy.

Public Health Relevance

Gestational Diabetes Mellitus (GDM) is tightly linked to overweight and obesity and is now diagnosed in as many as 7% of pregnancies in the US. In this project, we will identify novel biomarkers that can reconstruct prenatal GDM exposure and profile future risks of childhood obesity and related cardiometabolic phenotypes. We will also measure the efficacy of a lifestyle intervention at both molecular and phenotype levels. Our results will generate new scientific knowledge that may pave the way for future efforts for the prevention of childhood obesity and cardiovascular diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK100790-04
Application #
9321192
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Linder, Barbara
Project Start
2014-08-01
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2019-07-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
Nisa, Hoirun; Qi, Kevin H T; Leng, Junhong et al. (2018) The Circadian Rhythm-Related MTNR1B Genotype, Gestational Weight Gain, and Postpartum Glycemic Changes. J Clin Endocrinol Metab 103:2284-2290
Liu, Huikun; Wang, Leishen; Zhang, Shuang et al. (2018) One-year weight losses in the Tianjin Gestational Diabetes Mellitus Prevention Programme: A randomized clinical trial. Diabetes Obes Metab 20:1246-1255
Li, Weiqin; Leng, Junhong; Liu, Huikun et al. (2018) Nomograms for incident risk of post-partum type 2 diabetes in Chinese women with prior gestational diabetes mellitus. Clin Endocrinol (Oxf) :
Shen, Yun; Wang, Peng; Wang, Leishen et al. (2018) Gestational diabetes with diabetes and prediabetes risks: a large observational study. Eur J Endocrinol 179:51-58
Wang, Jing; Liu, Enqing; Wang, Yue et al. (2018) Association of early pregnancy body mass index and children's birth weight with risk of being overweight in childhood. Am J Hum Biol 30:e23174
Han, Liyuan; Duan, Donghui; Zhang, Shuang et al. (2018) Effects of the interaction between glycated haemoglobin genetic risk score and postpartum weight reduction on glycaemic changes: A gene-weight interaction analysis. Diabetes Obes Metab 20:2733-2739
Zhang, S; Wang, L; Leng, J et al. (2017) Hypertensive disorders of pregnancy in women with gestational diabetes mellitus on overweight status of their children. J Hum Hypertens 31:731-736
Zhang, Tao; Wang, Peng; Liu, Huikun et al. (2017) Physical Activity, TV Watching Time, Sleeping, and Risk of Obesity and Hyperglycemia in the Offspring of Mothers with Gestational Diabetes Mellitus. Sci Rep 7:41115
Li, Weiqin; Wang, Leishen; Li, Nan et al. (2017) Maternal Prepregnancy BMI and Glucose Level at 24-28 Gestational Weeks on Offspring's Overweight Status within 3 Years of Age. Biomed Res Int 2017:7607210
Leng, Junhong; Wang, Leishen; Wang, Jing et al. (2017) Uric acid and diabetes risk among Chinese women with a history of gestational diabetes mellitus. Diabetes Res Clin Pract 134:72-79

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