Fetal life is considered one of the critical (or sensitive) periods when an exposure may have lifelong effects. Increased adiposity in later life seems to occur at both ends of the birth weigh spectrum: generalized obesity with higher birth weight and increased visceral adiposity and its metabolic consequences at lower birth weights. Whether or not these phenotypes are detectable in exposed children and whether or not they have common biologic pathways is a focus of this proposal.
The specific aims of this proposal are:
Aim No. 1: To examine in parallel the long-term consequences of intrauterine exposure to excess nutrition (maternal diabetes) and under nutrition (growth restriction) on/childhood body size, fat patterning and markers of insulin resistance, among children of different ethnic groups.
Aim No. 2. To explore hypothesis of intrauterine hormonal """"""""programming"""""""" through which fetal exposures could increase the risk of obesity and insulin resistance in children. The proposed project is a prospective study proposing to enroll a total of 810 eight to eleven-year old offspring of diabetic pregnancies (exposed group-1), offspring of non-diabetic pregnancies with intrauterine growth restraint (exposed group-2), and control children (unexposed group), as well as their biological mothers, in three ethnic groups (non-Hispanic whites, Hispanics, and African-Americans). Comparison of exposed and unexposed groups will allow assessment and disentangling of the effects of exposure to diabetes mellitus in utero and intrauterine growth restraint on body size, fat patterning and insulin resistance markers and features later in childhood. The proposed research should also help understand whether these exposures have direct biological influences or are mediated through lifestyle choices. Such studies could ultimately lead to the development of strategies for early life prevention of future chronic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK068001-05
Application #
7650124
Study Section
Special Emphasis Panel (ZRG1-HOP-N (90))
Program Officer
Silva, Corinne M
Project Start
2005-09-14
Project End
2012-02-29
Budget Start
2009-07-01
Budget End
2012-02-29
Support Year
5
Fiscal Year
2009
Total Cost
$194,025
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Yang, I V; Zhang, W; Davidson, E J et al. (2018) Epigenetic marks of in utero exposure to gestational diabetes and childhood adiposity outcomes: the EPOCH study. Diabet Med 35:612-620
Stanislawski, Maggie A; Lozupone, Catherine A; Wagner, Brandie D et al. (2018) Gut microbiota in adolescents and the association with fatty liver: the EPOCH study. Pediatr Res 84:219-227
Felix, Janine F; Joubert, Bonnie R; Baccarelli, Andrea A et al. (2018) Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. Int J Epidemiol 47:22-23u
Dabelea, Dana (2018) Diabetes in Youth-Looking Backwards to Inform the Future: Kelly West Award Lecture 2017. Diabetes Care 41:233-240
Sauder, K A; Hockett, C W; Ringham, B M et al. (2017) Fetal overnutrition and offspring insulin resistance and ?-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study. Diabet Med 34:1392-1399
Cree-Green, Melanie; Cai, Ninghe; Pyle, Laura et al. (2017) Insulin Resistance in Youth Without Diabetes Is Not Related to Muscle Mitochondrial Dysfunction. J Clin Endocrinol Metab 102:1652-1660
Raghavan, S; Zhang, W; Yang, I V et al. (2017) Association between gestational diabetes mellitus exposure and childhood adiposity is not substantially explained by offspring genetic risk of obesity. Diabet Med 34:1696-1700
Shapiro, Allison L B; Sauder, Katherine A; Tregellas, Jason R et al. (2017) Exposure to maternal diabetes in utero and offspring eating behavior: The EPOCH study. Appetite 116:610-615
Kaar, Jill L; Crume, Tessa; Brinton, John T et al. (2014) Maternal obesity, gestational weight gain, and offspring adiposity: the exploring perinatal outcomes among children study. J Pediatr 165:509-15
Kaar, J L; Brinton, J T; Crume, T et al. (2014) Leptin levels at birth and infant growth: the EPOCH study. J Dev Orig Health Dis 5:214-8

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