Precision Nutrition and Metabolic Function

NCT04131166 | Active Not Recruiting DMC

• 1 other identifier: 201908237
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this study are: 1) to determine the mechanisms responsible for the development of cardiometabolic complications in some, but not all people with obesity; 2) determine the best dietary approach for cardiometabolic health; and 3) understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.

Conditions

Obesity; Insulin Resistance

Outcome Measures

Primary Outcomes (3)

• Insulin sensitivity

  Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure

  Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).

• Change in insulin sensitivity

  Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure

  Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet

• Change in insulin sensitivity

  Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure

  Performed annually for 5 years

Secondary Outcomes (38)

• 24-hour glucose concentrations

  Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).

• Change in 24-hour glucose concentrations

  Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet

• Change in 24-hour glucose concentrations

  Performed annually for 5 years

• 24-hour hormone concentrations

  Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).

• Change in 24-hour hormone concentrations

  Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet

Study Arms (7)

Metabolically healthy lean

OTHER

Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content.

Other: Annual follow-up testing for 5 years

Metabolically healthy obese - Mediterranean diet

EXPERIMENTAL

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the Mediterranean diet group.

Behavioral: Mediterranean diet; Other: Annual follow-up testing for 5 years

Metabolically healthy obese - Low-carbohydrate ketogenic diet

EXPERIMENTAL

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-carbohydrate ketogenic diet group.

Behavioral: Low-carbohydrate, ketogenic diet; Other: Annual follow-up testing for 5 years

Metabolically normal obese - Low-fat diet

EXPERIMENTAL

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-fat diet group.

Behavioral: Low-fat diet; Other: Annual follow-up testing for 5 years

Metabolically unhealthy obese - Mediterranean diet

EXPERIMENTAL

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the Mediterranean diet group.

Behavioral: Mediterranean diet; Other: Annual follow-up testing for 5 years

Metabolically unhealthy obese - Low-carbohydrate ketogenic diet

EXPERIMENTAL

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-carbohydrate, ketogenic diet group.

Behavioral: Low-carbohydrate, ketogenic diet; Other: Annual follow-up testing for 5 years

Metabolically unhealthy obese - Low-fat diet

EXPERIMENTAL

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-fat diet group.

Behavioral: Low-fat diet; Other: Annual follow-up testing for 5 years

Interventions

Mediterranean diet BEHAVIORAL

A Mediterranean-type diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.

Metabolically healthy obese - Mediterranean diet; Metabolically unhealthy obese - Mediterranean diet

Low-carbohydrate, ketogenic diet BEHAVIORAL

A low-carbohydrate, ketogenic diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.

Metabolically healthy obese - Low-carbohydrate ketogenic diet; Metabolically unhealthy obese - Low-carbohydrate ketogenic diet

Low-fat diet BEHAVIORAL

A low-fat diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.

Metabolically normal obese - Low-fat diet; Metabolically unhealthy obese - Low-fat diet

Annual follow-up testing for 5 years OTHER

Annual follow-up testing with no restrictions on dietary intake during periods between annual testing.

Metabolically healthy lean; Metabolically healthy obese - Low-carbohydrate ketogenic diet; Metabolically healthy obese - Mediterranean diet; Metabolically normal obese - Low-fat diet; Metabolically unhealthy obese - Low-carbohydrate ketogenic diet; Metabolically unhealthy obese - Low-fat diet; Metabolically unhealthy obese - Mediterranean diet

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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%.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Centene Corporation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Mittendorfer B, Patterson BW, Smith GI, Yoshino M, Klein S. beta Cell function and plasma insulin clearance in people with obesity and different glycemic status. J Clin Invest. 2022 Feb 1;132(3):e154068. doi: 10.1172/JCI154068.

  PMID: 34905513 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance

Interventions

Diet, Mediterranean; Diet, Ketogenic; Diet, Fat-Restricted

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet, Carbohydrate-Restricted

Study Officials

• Samuel Klein, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 18, 2019
• Study Start: October 8, 2019
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

US (1)