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Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance

Primary Purpose

Diabetes Mellitus, Type 2, PreDiabetes, Insulin Resistance

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Dietary Intervention Mediterranean Low Carbohydrate Diet
Dietary Intervention Standard Low Carbohydrate Diet
Dietary Intervention Standard Low Fat Diet
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diabetes Mellitus, Type 2 focused on measuring Metabolomics, Low Fat Diet, Low Carbohydrate Diet, Microbiome

Eligibility Criteria

35 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Age 35-65
  • BMI 25-35 kg/m2
  • Stable body weight
  • Nondiabetic

Exclusion Criteria:

Patients with;

  • diabetes
  • major organ disease
  • history of liposuction or bariatric surgery
  • active eating or psychiatric disorder
  • pregnancy or lactation, heavy alcohol use
  • recent change in weight (over the past 12 weeks)
  • use of weight loss medication, statins, or oral steroids

Clinical screening exclusions;

  • hematocrit < 33%
  • fasting glucose >/= 126 mg/dL
  • blood pressure >160/100 mmHg

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Mediterranean Low Carbohydrate Diet

Standard Low Carbohydrate Diet

Low Fat, Healthy Carbohydrate Diet

Arm Description

Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Outcomes

Primary Outcome Measures

Change from baseline on the 2-stage Steady State Plasma Glucose test
Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention
Change from peak weight on the 2-stage Steady State Plasma Glucose test
Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention
Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA
Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay
Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay
Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention

Secondary Outcome Measures

Full Information

First Posted
July 3, 2018
Last Updated
April 26, 2023
Sponsor
Stanford University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT05165706
Brief Title
Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
Official Title
Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 31, 2019 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

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

5. Study Description

Brief Summary
This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.
Detailed Description
Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, PreDiabetes, Insulin Resistance, Obesity, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver, Diet Modification
Keywords
Metabolomics, Low Fat Diet, Low Carbohydrate Diet, Microbiome

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Mediterranean Low Carbohydrate Diet
Arm Type
Experimental
Arm Description
Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Arm Title
Standard Low Carbohydrate Diet
Arm Type
Experimental
Arm Description
Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Arm Title
Low Fat, Healthy Carbohydrate Diet
Arm Type
Experimental
Arm Description
Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Intervention Type
Behavioral
Intervention Name(s)
Dietary Intervention Mediterranean Low Carbohydrate Diet
Intervention Description
Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Intervention Type
Behavioral
Intervention Name(s)
Dietary Intervention Standard Low Carbohydrate Diet
Intervention Description
Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Intervention Type
Behavioral
Intervention Name(s)
Dietary Intervention Standard Low Fat Diet
Intervention Description
Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Primary Outcome Measure Information:
Title
Change from baseline on the 2-stage Steady State Plasma Glucose test
Description
Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention
Time Frame
Peak weight (4 weeks)
Title
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Description
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention
Time Frame
Peak weight (4 weeks)
Title
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Description
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention
Time Frame
Peak weight (4 weeks)
Title
Change from peak weight on the 2-stage Steady State Plasma Glucose test
Description
Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention
Time Frame
Post-weight loss (8 weeks)
Title
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Description
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention
Time Frame
Post-weight loss (8 weeks)
Title
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Description
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention
Time Frame
Post-weight loss (8 weeks)
Title
Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA
Description
Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Time Frame
Baseline
Title
Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay
Description
Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Time Frame
Baseline
Title
Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay
Description
Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention
Time Frame
Peak Weight (4 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 35-65 BMI 25-35 kg/m2 Stable body weight Nondiabetic Exclusion Criteria: Patients with; diabetes major organ disease history of liposuction or bariatric surgery active eating or psychiatric disorder pregnancy or lactation, heavy alcohol use recent change in weight (over the past 12 weeks) use of weight loss medication, statins, or oral steroids Clinical screening exclusions; hematocrit < 33% fasting glucose >/= 126 mg/dL blood pressure >160/100 mmHg
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ekrem M Ayhan, BS
Phone
908-619-5381
Email
ayhane@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Dalia Perelman, MS, RD
Email
daliap@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tracey McLaughlin, MD
Organizational Affiliation
Stanford University, Department of Medicine, Division of Endocrinology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ekrem M Ayhan, BS
Phone
908-619-5381
Email
ayhane@stanford.edu
First Name & Middle Initial & Last Name & Degree
Dalia Perelman, MS, RD
Email
daliap@stanford.edu
First Name & Middle Initial & Last Name & Degree
Tracey L McLaughlin, MD, MS

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance

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