Advisor(s)

Paula Chandler-Laney

Committee Member(s)

Ashley Battarbee
Daniel Smith Jr
Gregory Pavela
W Timothy Garvey

Document Type

Dissertation

Date of Award

6-1-2026

Degree Name

Doctor of Philosophy (PhD)

School

School of Health Professions

Department

Nutrition Sciences

Abstract

Background: Childhood obesity increases risk for diseases including type 2 diabetes and cardiovascular disease. The in utero environment plays an important role in the metabolic programming of offspring, with children exposed to maternal obesity or gestational diabetes (GDM) having high risk for obesity. In adults, metabolic mechanisms such as leptin resistance, energy expenditure, and substrate oxidation are associated with prospective weight and adiposity gain, but less is known in children. Thus, the purpose of this study is to identify metabolic mechanisms associated with risk for obesity following in utero exposure to maternal obesity, with or without exposure to GDM. Methods: A cohort of N=221 children (4-10 years) were recruited and grouped according to maternal pre-pregnancy BMI and GDM status. The groups were as follows: 1) maternal normal weight and no GDM, 2) maternal overweight or obesity and no GDM, or 3) maternal overweight or obesity with GDM. A fasting blood draw was obtained from which to measure leptin concentrations, and children underwent dual-energy X-ray absorptiometry (DXA) to assess body composition, and indirect calorimetry to assess resting and post-meal energy expenditure and respiratory exchange ratio. Children returned 3 years later for a follow-up DXA. Results: Findings from Aim 1 demonstrate that the child’s current weight status, but not in utero exposure to maternal obesity or GDM, was associated with leptin resistance where children with obesity had greater leptin resistance compared to children with normal weight. In Aim 2, in utero exposure to GDM was associated with less meal-induced energy expenditure and metabolic inflexibility. In Aim 3, baseline leptin resistance, energy expenditure, and substrate oxidation at 4-10 years were not associated with 3-year prospective adiposity gain. Conclusion: Our findings suggest that blunted thermic effect of food and metabolic inflexibility may contribute to weight and adiposity gain in children exposed in utero to GDM compared to children born to women with no GDM. Future studies should continue to explore additional mechanisms that may contribute to adiposity gain in high-risk children in the hopes of developing tailored interventions to treat, or even prevent obesity development.

Keywords

early life programming;intrauterine environment;metabolism;offspring adiposity

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