Maternal GDM in Hispanic Youth: Risk for Obesity

Study Overview
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Brief Summary
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Our studies are aimed at examining effects of intrauterine exposure to GDM on metabolic risks in Hispanic children. Our primary hypothesis predicts that intrauterine exposure to GDM will be associated with one or more of three critical factors involved in the development of diabetes: 1) increased adiposity, 2) insulin resistance, and 3) decreased beta cell function in Hispanic children when compared to non-exposed children matched for ethnicity, age, gender, and Tanner stage. In a subset of this cohort, we will also examine the effects of intrauterine exposure to gestational diabetes on the brain pathways that regulate appetite and body weight in children ages 6 to 15 years old.

Detailed Description
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Obesity rates have increased dramatically over the last two decades, particularly in children. Obesity is a major risk factor for type 2 diabetes (T2D), and there is a disproportionate prevalence of obesity and T2D in people of Hispanic origin. While a number of factors contribute to the development of obesity and T2D there is compelling evidence suggesting a profound role of the diabetic in utero environment. Epidemiological studies show that exposure to maternal diabetes in utero is associated with a significant risk of developing obesity and diabetes later in life. Provocative studies in animal models suggest that metabolic imprinting resulting from exposure to the altered metabolic milieu of diabetes in pregnancy leads to abnormalities in the development of specific fetal tissues, including the hypothalamus and pancreatic islets. Based on these findings, the goal of this research is to test the hypothesis that exposure to maternal gestational diabetes mellitus in utero results in changes during intrauterine development that mediate increased risk for obesity and diabetes. Through our ongoing studies on the genetics of type 2 diabetes we have access to hundreds of Hispanic offspring of well characterized GDM and control mothers. We are, therefore, in the unique position to perform mechanistic studies examining effects of intrauterine exposure to GDM on metabolic risks in Hispanic children and adolescents. Our primary hypothesis predicts that intrauterine exposure to GDM will be associated with one or more of three critical factors involved in the development of diabetes: 1) increased adiposity, 2) insulin resistance, and 3) decreased beta cell function in Hispanic children when compared to non-exposed children matched for ethnicity, age, gender, and Tanner stage. To examine the effects of exposure to GDM on brain pathways involved in the regulation of energy homeostasis, we will perform additional functional magnetic resonance imaging (fMRI) studies in a subset of the larger cohort.

Official Title
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Maternal Gestational Diabetes in Hispanic Youth: Obesity and Insulin Resistance

Conditions
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Diabetes, Gestational, Obesity, Insulin Resistance, Insulin Secretion

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Offspring between the ages of 4 and 18 years old who were born to women who participated in the BetaGene Study. Exclusion Criteria: Offspring < 4 or > 18 years of age; gestation < 36 weeks at birth; significant medical illness and/or current use of medication known to influence glucose tolerance or BMI.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GDM Exposed<br>Children exposed to gestational diabetes in utero | |
| Non-GDM Exposed<br>Children not exposed to gestational diabetes in utero | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adiposity | BMI (z-score) and total body fat | Day 1 | 
| insulin sensitivity | OGTT | Day 2 | 
| insulin secretion | OGTT | Day 2 | 
| hypothalamic CBF | fMRI | Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gestational Diabetes Mellitus, Childhood Obesity, Offspring