Understanding how diet affects metabolic health in obesity

Precision Nutrition and Metabolic Function

This study is testing different diets to see how they can help people with obesity improve their heart and metabolic health over five years.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Washington University School of Medicine (other)
• Locations: 1 site (Saint Louis, Missouri)
• Trial ID: NCT04131166 on ClinicalTrials.gov

What this trial studies

This study aims to explore the mechanisms behind cardiometabolic complications in individuals with obesity and to identify the most effective dietary approaches for improving cardiometabolic health. Participants will be categorized into three groups based on their metabolic health status: metabolically normal lean, metabolically normal obese, and metabolically abnormal obese. The study will involve various dietary interventions, including a Mediterranean diet, low-carbohydrate ketogenic diet, and low-fat diet, with annual follow-up assessments over five years to monitor changes in metabolic function. The goal is to understand why some individuals maintain metabolic health while others do not.

Who should consider this trial

Good fit: Ideal candidates for this study include adults with varying degrees of obesity, specifically those who are metabolically healthy or unhealthy based on specific metabolic criteria.

Not a fit: Patients who are underweight or have undergone significant gastrointestinal surgeries may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized dietary recommendations that improve metabolic health and reduce the risk of type 2 diabetes and cardiovascular disease in individuals with obesity.

How similar studies have performed: Other studies have shown promising results in understanding dietary impacts on metabolic health, but this approach of categorizing individuals based on metabolic health status is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Metabolically healthy lean subjects must have a body mass index (BMI) 18.5-24.9 kg/m2, intrahepatic triglyceride (IHTG) content ≤5%, serum triglyceride (TG) concentration \<150 mg/dl, fasting plasma glucose concentration \<100 mg/dl, 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
* Metabolically healthy obese subjects must have a BMI 30-49.9 kg/m2; IHTG content ≤5%, serum TG concentration \<150 mg/dl, fasting plasma glucose concentration \<100 mg/dl, 2-hr OGTT plasma glucose concentration ≤140 mg/dl, and HbA1C ≤5.6%.
* Metabolically unhealthy obese subjects must have a BMI 30-49.9 kg/m2; IHTG content ≥5.6% and fasting plasma glucose concentration ≥100 mg/dl or 2-hr OGTT plasma glucose concentration ≥140 mg/dl or HbA1C ≥5.7%.

Exclusion Criteria:

* medical, surgical, or biological menopause;
* previous bariatric surgery where the gastrointestinal tract is reconstructed such as Roux-en-Y, sleeve gastrectomy and biliopancreatic diversion surgeries;
* laparoscopic adjustable gastric band (lab band) surgery within the last 3 years;
* structured exercise ≥250 min per week (e.g., brisk walking);
* unstable weight (\>4% change during the last 2 months before entering the study);
* significant organ system dysfunction (e.g., diabetes requiring medications, severe pulmonary, kidney or cardiovascular disease);
* cancer or cancer that has been in remission for \<5 years;
* polycystic ovary syndrome;
* major psychiatric illness;
* conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders);
* severe anemia;
* regular use of tobacco products;
* excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women);
* use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study;
* use of antibiotics in last 60 days;
* pregnant or lactating women;
* vegans, vegetarians, those with lactose intolerance and/or severe aversions/sensitivities to eggs, fish, nuts, wheat and soy, and/or any individuals with food allergies that induce an anaphylactic response;
* persons who are not able to grant voluntary informed consent

Where this trial is running

Saint Louis, Missouri

• Washington University School of Medicine — Saint Louis, Missouri, United States (RECRUITING)

Study contacts

• Principal investigator: Samuel Klein, MD — Washington University School of Medicine
• Study coordinator: Brittney Mason

Conditions: Obesity, Insulin Resistance