Metabolic Adaptations to High-fat Diet (MetFlexHFD)

Adaptations in Postprandial Metabolic Flexibility Following a Three-day, High-fat Diet

The purpose of this study is to understand how the body's response after a meal is influenced by insulin and sugar in the blood. The primary question this study seeks to address is what is the effect of reduced insulin sensitivity on postprandial metabolic flexibility to an oral glucose tolerance test. We will recruit 50 adults (ages 20-45; 50% female) who are otherwise healthy (no known clinical diagnosis) into our non-randomized crossover trial to determine the effect of changes in insulin sensitivity on metabolic response to feeding. Insulin sensitivity will be decreased using a three-day high-fat diet (HFD) with extra calories. Whole-body metabolism will be measured during a standard 75-gram oral glucose tolerance test (OGTT). Metabolic response to feeding (e.g. OGTT) will be compared before and after the HFD and compared with the control diet to understand the effect of decreased insulin sensitivity on the metabolic response to feeding. The role of biological sex as a moderator of the effect of increased insulin resistance on postprandial metabolic flexibility will also be investigated

Study Overview

• Status: Terminated
• Conditions: Adiposity; Impaired Glucose Tolerance; Insulin Sensitivity; Metabolic Disturbance
• Intervention / Treatment: Behavioral: Hypercaloric, High Fat Diet

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20052
      • George Washington University School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males or Females between the ages of 20 and 45 years
• Body mass index (BMI) of 18.5-29.9 kg/m2
• Low risk for medical complications as determined by physical activity readiness questionnaire (PARQ).
• Low risk for food insecurity via the Hunger Vital Sign screener

Exclusion Criteria:

• Currently taking any antioxidant supplementation, prescription non-steroidal anti- inflammatory drugs, antibiotics, steroids, probiotics, medications for management of cholesterol, diabetes, body weight/obesity, or are undergoing transgender hormone therapy.
• Currently pregnant (verified by urine pregnancy test)
• Any history of disordered eating (i.e., anorexia nervosa, bulimia nervosa, binge eating disorder, etc.) or high risk for disordered eating via validated questionnaire (SCOFF)
• Any history of gastrointestinal diseases (i.e., gastroesophageal reflux disease, irritable bowel syndrome, Celiac disease, Crohn's disease, or lactose intolerance)
• Allergies to wheat or gluten, milk, soy, tree nuts (e.g., almonds, walnuts, pecans), or peanuts.
• Followed a ketogenic diet within the last three months
• Instructed by a medical provided to avoid a high-fat diet due to cardiovascular disease risk.
• Cardiorespiratory fitness (VO2max) greater than the 90th percentile for age and sex

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypercaloric, High Fat Diet; For three calendar days participants will be asked to track all foods they eat and beverages they drink (habitual diet) in a mobile application. Following the three days following the habitual diet, participants will consume 165% of their estimated daily energy needs with 65% of those calories coming from fat.

Behavioral: Hypercaloric, High Fat Diet; Participants will select meals from a list of sample breakfast, lunch, and dinner options from grocery stores. Typical intake will be estimated as 160-170% of resting metabolic rate, which will then be multiplied by 1.65 as the target calorie intake for the HFD. Target fat intake will be 65% of the HFD calorie target. To ensure participants will achieve the desired calorie and fat intake, they will also be provided with pre-made nutrient shakes and half-and-half. Participants will supplement their food intake with one to three shakes per day for each of the three days, depending on the fat and calorie content of the foods they select. They will be asked to add half-and-half equally between across the shakes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial Metabolic Flexibility	Mean difference respiratory exchange ratio during an oral glucose tolerance test following a high fat diet	3 Days

Collaborators and Investigators

• Sponsor: George Washington University
• Investigators: Principal Investigator: Matthew D Barberio, PhD, George Washington University

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2024
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 1, 2024
• First Posted (Actual): August 5, 2024

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Insulin Sensitivity; Metabolism; Substrate Oxidation; Feeding; High Fat Diet; Metabolic Flexibility
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Insulin Resistance; Glucose Intolerance; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet; Diet, High-Fat
• Other Study ID Numbers: NCR245732

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No