High-fat Meal Challenge in Pediatrics

Study Overview
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Brief Summary
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The objective is to determine if how physical fitness, measured using a treadmill maximal oxidative capacity test, is associated with the capacity to metabolize a high-fat meal in pediatrics (ages 8-17 years). Ability to metabolize the meal will be assessed by profiling mitochondrial and extra-mitochondrial fatty acid metabolites. The investigators will test if fatty acid oxidation mediates the relationship between fitness and markers of metabolic health, such as insulin resistance.

Official Title
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Implications of Insulin Resistance and Cardiorespiratory Fitness in the Metabolic Response to a High-fat Meal Challenge in Pediatrics

Conditions
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Pediatric Obesity, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: High-fat Challenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children ages 8-17 years with a BMI-percentile ≥ 5th. Exclusion Criteria: Previous diagnosis of type 1 or 2 diabetes. Use of concurrent medications known to affect glucose metabolism (metformin, oral steroids, sulfonylureas, insulin). Evidence of inherited disorders of lipid metabolism. Inability to participant in the maximal aerobic capacity test on the treadmill. Allergies to palm oils or protein types within high-fat challenge, such as lactose and soy. Individuals who cannot speak and/or write in English.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 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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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-fat Metabolic Challenge<br>Participants will consume a high-fat agent one time, at the second study visit. | Dietary Supplement: High-fat Challenge<br>* The shake will be composed of a mixture of BOOST Glucose Control(R) (Nestlé Products) supplemented with palm oil. Each participant will consume a volume of liquid equivalent to 25% of their estimated daily caloric needs, calculated by the USDA Dietary Reference Intakes using a moderate activity factor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if the interaction between daily physical activity and dietary intake mediates the correlation between VO2 max and body composition - as measured by daily physical activity. | Protocol: Children, aged 8-17 years (body mass index (BMI) percentile ≥ 85% for sex/age, matched with leans [5%≤BMI percentile<85%], n=50), will be recruited. Over seven days, participants will be asked to wear an ActiGraph accelerometer (ActiGraph, Pensacola, FL) and complete three dietary recalls. Analysis: Daily time spent in moderate to vigorous physical activity will be calculated (minutes). The average daily time in moderate to vigorous physical activity will be calculated across 7 days (minutes). | Up to 7 days | 
| Determine if the interaction between daily physical activity and dietary intake mediates the correlation between VO2 max and body composition - as measured by daily dietary intake. | Protocol: Children, aged 8-17 years (body mass index (BMI) percentile ≥ 85% for sex/age, matched with leans [5%≤BMI percentile<85%], n=50), will be recruited. Over seven days, participants will be asked to wear an ActiGraph accelerometer (ActiGraph, Pensacola, FL) and complete three dietary recalls. Analysis: Daily dietary intake will be scored using the Healthy Eating Index (scale: 1-12). The average Healthy Eating Index score will be calculated across the 3 days of collected data (scale: 1-12) | Up to 7 days | 
| Determine if the interaction between daily physical activity and dietary intake mediates the correlation between VO2 max and body composition - as measured by VO2 max. | Protocol: Children, aged 8-17 years (body mass index (BMI) percentile ≥ 85% for sex/age, matched with leans [5%≤BMI percentile<85%], n=50), will be recruited. Stress testing will use a modified Bruce protocol, increasing in elevation and speed, to measure maximal oxygen consumption (VO2 max). VO2 max describes the milliliters of oxygen consumed in one minute of exercise, per kilogram of body weight (units: mL/min/kg). | Up to 7 days | 
| Determine if the interaction between daily physical activity and dietary intake mediates the correlation between VO2 max and body composition - as measured by body composition. | Protocol: Children, aged 8-17 years (body mass index (BMI) percentile ≥ 85% for sex/age, matched with leans [5%≤BMI percentile<85%], n=50), will be recruited. Body composition will be measured using bioelectrical impedance (Seca, Hamburg, Germany). Percent fat mass will be calculated (%) Analysis: Investigators will determine if the interaction between daily physical activity (minutes) and daily dietary intake (score: 1-12) mediates the correlation between VO2 max (mL/min/kg) and body fat percentage (%). Outcome units will describe a linear correlation. | Up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the correlation between fatty acid oxidation and VO2 max. | Protocol: After an overnight fast, participants will consume the high-fat (HF) challenge, composed of palm oil supplemented Boost® (15% kcal carbohydrates, 15% kcal protein, 70% kcal lipid). Blood will be sampled via intravenous line at baseline (0 minutes) and after consuming the challenge (30, 60, 120, and 180 minutes). The investigators will conduct targeted metabolomics on all blood samples, profiling acylcarnitines (AC) and dicarboxylic fatty acid (FA-COOH) metabolites. Analysis: Longitudinal trajectories, measured by empirical Bayes time-series analysis, will quantify the response of metabolites to the challenge. Mixed regression models will determine the correlation between VO2 max (mL/min/kg) and metabolite trajectories. Outcome units will describe a linear correlation. | Five blood draws (fasting, 30 minutes, 60 minutes, 120 minutes, and 180 minutes) all completed on 1 day |