ObesityNCT04131166
Precision Nutrition and Metabolic Function
A study testing Mediterranean diet, Low-carbohydrate, ketogenic diet and Low-fat diet in people with Obesity and Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Insulin Resistance
- What is being tested?
- Mediterranean diet, Low-carbohydrate, ketogenic diet and Low-fat diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2019to 31 Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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%.
Who cannot join
- 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);
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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.
Read the detailed description
Excess adiposity causes alterations in metabolic function including impaired glucose homeostasis and insulin resistance, which are important risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). Not all people with obesity experience the typical metabolic complications associated with obesity. Approximately 25% of people with obesity are protected from the adverse metabolic effects of excess fat accumulation and are considered to be metabolically healthy based on their normal response to insulin. The mechanism(s) responsible for the differences in metabolic function among people with obesity is not known, but is likely to be multifactorial including dietary intake. The risk for developing T2D and CVD is also well known to increase with age, however, not all people that are metabolically healthy convert to a metabolically unhealthy phenotype over time. The mechanisms responsible for the stability of health status in some, but not all adults, are unclear. The overall goals of this study are to: i) determine the mechanisms responsible for the development of cardiometabolic complications in participants who will be carefully characterized into 3 distinct groups [metabolically normal lean, metabolically normal obese and metabolically abnormal obese], ii) to determine the optimal dietary approach for cardiometabolic health independent of weight change in people with metabolically abnormal obesity, and iii) perform a comprehensive longitudinal assessment of cardiometabolic health to understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.
- Conditions
- Obesity, Insulin Resistance
- Being tested
- Mediterranean diet, Low-carbohydrate, ketogenic diet, Low-fat diet, Annual follow-up testing for 5 years
- Medical subject headings
- Obesity, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mediterranean dietBehavioural
A Mediterranean-type diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
Low-carbohydrate, ketogenic dietBehavioural
A low-carbohydrate, ketogenic diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
Low-fat dietBehavioural
A low-fat diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
Annual follow-up testing for 5 yearsOther
Annual follow-up testing with no restrictions on dietary intake during periods between annual testing.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Behavioral: Low-fat diet; Other: Annual follow-up testing for 5 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: 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
Measured: 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
Measured: Performed annually for 5 years
Secondary outcomes (38)
24-hour glucose concentrations
Plasma glucose concentrations will be evaluated from frequent blood samples over a 24 h period
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in 24-hour glucose concentrations
Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period
Measured: 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
Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period
Measured: Performed annually for 5 years
24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood sampling over a 24 h period
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in 24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period
Measured: 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 hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period
Measured: Performed annually for 5 years
β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Measured: Performed annually for 5 years
Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Measured: Performed annually for 5 years
Fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Measured: 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 fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Measured: Performed annually for 5 years
Exosome-mediated intercellular signaling
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in exosome-mediated intercellular signaling
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Measured: 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 exosome-mediated intercellular signaling
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Measured: Performed annually for 5 years
Intrahepatic triglyceride content
Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Measured: 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 intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Measured: Performed annually for 5 years
Abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: 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 abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Performed annually for 5 years
Leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: 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 leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Performed annually for 5 years
Gut microbiome
Gut microbiota, meta-transcriptome (bacterial RNA sequencing to determine what proteins can be made by the microbiota) and the meta-metabolome (metabolites made by the microbiota) will be assessed
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in gut microbiome
Gut microbiota, meta-transcriptome (bacterial RNA sequencing to determine what proteins can be made by the microbiota) and the meta-metabolome (metabolites made by the microbiota) will be assessed
Measured: 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 gut microbiome
Gut microbiota, meta-transcriptome (bacterial RNA sequencing to determine what proteins can be made by the microbiota) and the meta-metabolome (metabolites made by the microbiota) will be assessed
Measured: Performed annually for 5 years
Carotid artery intima media thickness
Carotid artery intima media thickness will be assessed by ultrasound imaging
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in carotid artery intima media thickness
Carotid artery intima media thickness will be assessed by ultrasound imaging
Measured: Performed annually for 5 years
Cardiac structure and function
Ultrasound techniques will be used to assess cardiac structure and function
Measured: Baseline only (cross-sectional comparison of metabolically healthy obese and metabolically unhealthy obese subjects).
Change in cardiac structure and function
Ultrasound techniques will be used to assess cardiac structure and function
Measured: Performed annually for 5 years in metabolically healthy obese and metabolically unhealthy obese subjects.
Endothelial function
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in endothelial function
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Measured: Performed annually for 5 years
Arterial stiffness
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in arterial stiffness
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Measured: Performed annually for 5 years
Transcriptome in blood, muscle and adipose tissue
The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in transcriptome in blood, muscle and adipose tissue
The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques
Measured: Performed annually for 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start8 Oct 2019
- Primary completion1 Oct 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Centene Corporation
- Responsible party
- Sponsor
- Investigators
- Samuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131166
- Sponsor's protocol ID
- 201908237
- Status last verified
- Jul 2026
- First submitted
- 15 Oct 2019
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34905513
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Nutrition and Metabolic Function
- ClinicalTrials.gov ID
- NCT04131166
- Acronym / sponsor ID
- 201908237
- Conditions
- Obesity, Insulin Resistance
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Centene Corporation
- Study start
- 8 Oct 2019 (actual)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 18 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Excess adiposity causes alterations in metabolic function including impaired glucose homeostasis and insulin resistance, which are important risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). Not all people with obesity experience the typical metabolic complications associated with obesity. Approximately 25% of people with obesity are protected from the adverse metabolic effects of excess fat accumulation and are considered to be metabolically healthy based on their normal response to insulin. The mechanism(s) responsible for the differences in metabolic function among people with obesity is not known, but is likely to be multifactorial including dietary intake. The risk for developing T2D and CVD is also well known to increase with age, however, not all people that are metabolically healthy convert to a metabolically unhealthy phenotype over time. The mechanisms responsible for the stability of health status in some, but not all adults, are unclear. The overall goals of this study are to: i) determine the mechanisms responsible for the development of cardiometabolic complications in participants who will be carefully characterized into 3 distinct groups [metabolically normal lean, metabolically normal obese and metabolically abnormal obese], ii) to determine the optimal dietary approach for cardiometabolic health independent of weight change in people with metabolically abnormal obesity, and iii) perform a comprehensive longitudinal assessment of cardiometabolic health to understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Metabolically healthy lean | Other | Other: Annual follow-up testing for 5 yearsMetabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. |
| Metabolically healthy obese - Mediterranean diet | Experimental | Behavioral: Mediterranean diet, Other: Annual follow-up testing for 5 yearsMetabolically 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. |
| Metabolically healthy obese - Low-carbohydrate ketogenic diet | Experimental | Behavioral: Low-carbohydrate, ketogenic diet, Other: Annual follow-up testing for 5 yearsMetabolically 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. |
| Metabolically normal obese - Low-fat diet | Experimental | Behavioral: Low-fat diet, Other: Annual follow-up testing for 5 yearsMetabolically 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. |
| Metabolically unhealthy obese - Mediterranean diet | Experimental | Behavioral: Mediterranean diet, Other: Annual follow-up testing for 5 yearsMetabolically 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. |
| Metabolically unhealthy obese - Low-carbohydrate ketogenic diet | Experimental | Behavioral: Low-carbohydrate, ketogenic diet, Other: Annual follow-up testing for 5 yearsMetabolically 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. |
| Metabolically unhealthy obese - Low-fat diet | Experimental | Behavioral: Low-fat diet, Other: Annual follow-up testing for 5 yearsMetabolically 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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%.
Key exclusion criteria (18 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mediterranean dietA Mediterranean-type diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided. | Behavioural | Metabolically healthy obese - Mediterranean diet, Metabolically unhealthy obese - Mediterranean diet |
| Low-carbohydrate, ketogenic dietA low-carbohydrate, ketogenic diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided. | Behavioural | Metabolically healthy obese - Low-carbohydrate ketogenic diet, Metabolically unhealthy obese - Low-carbohydrate ketogenic diet |
| Low-fat dietA low-fat diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided. | Behavioural | Metabolically normal obese - Low-fat diet, Metabolically unhealthy obese - Low-fat diet |
| Annual follow-up testing for 5 yearsAnnual follow-up testing with no restrictions on dietary intake during periods between annual testing. | Other | 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 |
Primary outcome
Insulin sensitivity
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Change in insulin sensitivity
Time frame: 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
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Change in insulin sensitivity
Time frame: Performed annually for 5 years
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
38 secondary outcomes
24-hour glucose concentrations
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in 24-hour glucose concentrations
Time frame: 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
Time frame: Performed annually for 5 years
24-hour hormone concentrations
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in 24-hour hormone concentrations
Time frame: 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 hormone concentrations
Time frame: Performed annually for 5 years
β-cell function
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in β-cell function
Time frame: Performed annually for 5 years
Insulin clearance
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in Insulin clearance
Time frame: Performed annually for 5 years
Fat mass and fat free mass
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in fat mass and fat free mass
Time frame: 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 fat mass and fat free mass
Time frame: Performed annually for 5 years
Exosome-mediated intercellular signaling
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in exosome-mediated intercellular signaling
Time frame: 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 exosome-mediated intercellular signaling
Time frame: Performed annually for 5 years
Intrahepatic triglyceride content
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in intra-hepatic triglyceride content
Time frame: 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 intra-hepatic triglyceride content
Time frame: Performed annually for 5 years
Abdominal adipose tissue volumes
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in abdominal adipose tissue volumes
Time frame: 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 abdominal adipose tissue volumes
Time frame: Performed annually for 5 years
Leg adipose tissue volumes
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in leg adipose tissue volumes
Time frame: 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 leg adipose tissue volumes
Time frame: Performed annually for 5 years
Gut microbiome
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in gut microbiome
Time frame: 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 gut microbiome
Time frame: Performed annually for 5 years
Carotid artery intima media thickness
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in carotid artery intima media thickness
Time frame: Performed annually for 5 years
Cardiac structure and function
Time frame: Baseline only (cross-sectional comparison of metabolically healthy obese and metabolically unhealthy obese subjects).
Change in cardiac structure and function
Time frame: Performed annually for 5 years in metabolically healthy obese and metabolically unhealthy obese subjects.
Endothelial function
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in endothelial function
Time frame: Performed annually for 5 years
Arterial stiffness
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in arterial stiffness
Time frame: Performed annually for 5 years
Transcriptome in blood, muscle and adipose tissue
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Change in transcriptome in blood, muscle and adipose tissue
Time frame: Performed annually for 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Derived from this study: PubMed 34905513Mittendorfer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Klein, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mediterranean diet, Low-carbohydrate, ketogenic diet and Low-fat diet in people with Obesity and Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity (time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04131166, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.