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Precision Nutrition and Metabolic Function

Primary Purpose

Obesity, Insulin Resistance

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Mediterranean diet
Low-carbohydrate, ketogenic diet
Low-fat diet
Annual follow-up testing for 5 years
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Obesity

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Other

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Metabolically healthy lean

Metabolically healthy obese - Mediterranean diet

Metabolically healthy obese - Low-carbohydrate ketogenic diet

Metabolically normal obese - Low-fat diet

Metabolically unhealthy obese - Mediterranean diet

Metabolically unhealthy obese - Low-carbohydrate ketogenic diet

Metabolically unhealthy obese - Low-fat diet

Arm Description

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

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

24-hour glucose concentrations
Plasma glucose concentrations will be evaluated from frequent blood samples over a 24 h period
Change in 24-hour glucose concentrations
Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period
Change in 24-hour glucose concentrations
Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period
24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood sampling over a 24 h period
Change in 24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period
Change in 24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period
β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Change in β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Change in Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Change in fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Change in fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Exosome-mediated intercellular signaling
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
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
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
Intrahepatic triglyceride content
Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Change in intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Change in intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Change in abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Change in abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Change in leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Change in leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
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
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
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
Carotid artery intima media thickness
Carotid artery intima media thickness will be assessed by ultrasound imaging
Change in carotid artery intima media thickness
Carotid artery intima media thickness will be assessed by ultrasound imaging
Cardiac structure and function
Ultrasound techniques will be used to assess cardiac structure and function
Change in cardiac structure and function
Ultrasound techniques will be used to assess cardiac structure and function
Endothelial function
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Change in endothelial function
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Arterial stiffness
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Change in arterial stiffness
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
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
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

Full Information

First Posted
October 15, 2019
Last Updated
August 4, 2023
Sponsor
Washington University School of Medicine
Collaborators
Centene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04131166
Brief Title
Precision Nutrition and Metabolic Function
Official Title
Precision Nutrition and Metabolic Function
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 8, 2019 (Actual)
Primary Completion Date
October 1, 2029 (Anticipated)
Study Completion Date
December 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Centene Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Insulin Resistance

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metabolically healthy lean
Arm Type
Other
Arm Description
Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content.
Arm Title
Metabolically healthy obese - Mediterranean diet
Arm Type
Experimental
Arm Description
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.
Arm Title
Metabolically healthy obese - Low-carbohydrate ketogenic diet
Arm Type
Experimental
Arm Description
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.
Arm Title
Metabolically normal obese - Low-fat diet
Arm Type
Experimental
Arm Description
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.
Arm Title
Metabolically unhealthy obese - Mediterranean diet
Arm Type
Experimental
Arm Description
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.
Arm Title
Metabolically unhealthy obese - Low-carbohydrate ketogenic diet
Arm Type
Experimental
Arm Description
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.
Arm Title
Metabolically unhealthy obese - Low-fat diet
Arm Type
Experimental
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Mediterranean diet
Intervention Description
A Mediterranean-type diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
Intervention Type
Behavioral
Intervention Name(s)
Low-carbohydrate, ketogenic diet
Intervention Description
A low-carbohydrate, ketogenic diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
Intervention Type
Behavioral
Intervention Name(s)
Low-fat diet
Intervention Description
A low-fat diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
Intervention Type
Other
Intervention Name(s)
Annual follow-up testing for 5 years
Intervention Description
Annual follow-up testing with no restrictions on dietary intake during periods between annual testing.
Primary Outcome Measure Information:
Title
Insulin sensitivity
Description
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in insulin sensitivity
Description
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
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
Title
Change in insulin sensitivity
Description
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Time Frame
Performed annually for 5 years
Secondary Outcome Measure Information:
Title
24-hour glucose concentrations
Description
Plasma glucose concentrations will be evaluated from frequent blood samples over a 24 h period
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in 24-hour glucose concentrations
Description
Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period
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
Title
Change in 24-hour glucose concentrations
Description
Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period
Time Frame
Performed annually for 5 years
Title
24-hour hormone concentrations
Description
Plasma hormone concentrations will be evaluated from frequent blood sampling over a 24 h period
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in 24-hour hormone concentrations
Description
Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period
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
Title
Change in 24-hour hormone concentrations
Description
Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period
Time Frame
Performed annually for 5 years
Title
β-cell function
Description
β-cell function will be assessed from a modified oral glucose tolerance test
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in β-cell function
Description
β-cell function will be assessed from a modified oral glucose tolerance test
Time Frame
Performed annually for 5 years
Title
Insulin clearance
Description
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in Insulin clearance
Description
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Time Frame
Performed annually for 5 years
Title
Fat mass and fat free mass
Description
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in fat mass and fat free mass
Description
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
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
Title
Change in fat mass and fat free mass
Description
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Time Frame
Performed annually for 5 years
Title
Exosome-mediated intercellular signaling
Description
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in exosome-mediated intercellular signaling
Description
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
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
Title
Change in exosome-mediated intercellular signaling
Description
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Time Frame
Performed annually for 5 years
Title
Intrahepatic triglyceride content
Description
Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in intra-hepatic triglyceride content
Description
Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
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
Title
Change in intra-hepatic triglyceride content
Description
Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Time Frame
Performed annually for 5 years
Title
Abdominal adipose tissue volumes
Description
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in abdominal adipose tissue volumes
Description
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
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
Title
Change in abdominal adipose tissue volumes
Description
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Time Frame
Performed annually for 5 years
Title
Leg adipose tissue volumes
Description
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in leg adipose tissue volumes
Description
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
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
Title
Change in leg adipose tissue volumes
Description
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Time Frame
Performed annually for 5 years
Title
Gut microbiome
Description
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
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in gut microbiome
Description
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
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
Title
Change in gut microbiome
Description
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
Time Frame
Performed annually for 5 years
Title
Carotid artery intima media thickness
Description
Carotid artery intima media thickness will be assessed by ultrasound imaging
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in carotid artery intima media thickness
Description
Carotid artery intima media thickness will be assessed by ultrasound imaging
Time Frame
Performed annually for 5 years
Title
Cardiac structure and function
Description
Ultrasound techniques will be used to assess cardiac structure and function
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in cardiac structure and function
Description
Ultrasound techniques will be used to assess cardiac structure and function
Time Frame
Performed annually for 5 years in metabolically healthy obese and metabolically unhealthy obese subjects.
Title
Endothelial function
Description
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in endothelial function
Description
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Time Frame
Performed annually for 5 years
Title
Arterial stiffness
Description
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in arterial stiffness
Description
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Time Frame
Performed annually for 5 years
Title
Transcriptome in blood, muscle and adipose tissue
Description
The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques
Time Frame
Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Title
Change in transcriptome in blood, muscle and adipose tissue
Description
The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques
Time Frame
Performed annually for 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johanna Sonnenschein
Phone
314-273-1879
Email
nutritionresearch@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel Klein, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Janet Winkelmann
Phone
314-286-2099
Email
janetwinkelmann@wustl.edu
First Name & Middle Initial & Last Name & Degree
Samuel Klein, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
34905513
Citation
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.
Results Reference
derived

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Precision Nutrition and Metabolic Function

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