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

NCT05165706 | Recruiting

• 2 other identifiers: 401955R01DK110186-02
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2; PreDiabetes; Insulin Resistance; Obesity; Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver; Diet Modification

Keywords

Metabolomics; Low Fat Diet; Low Carbohydrate Diet; Microbiome

Outcome Measures

Primary Outcomes (9)

• 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

  Peak weight (4 weeks)

• 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

  Peak weight (4 weeks)

• 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

  Peak weight (4 weeks)

• 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

  Post-weight loss (8 weeks)

• 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

  Post-weight loss (8 weeks)

• 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

  Post-weight loss (8 weeks)

• 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.

  Baseline

• 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.

  Baseline

• 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

  Peak Weight (4 weeks)

Study Arms (3)

Mediterranean Low Carbohydrate Diet

EXPERIMENTAL

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.

Behavioral: Dietary Intervention Mediterranean Low Carbohydrate Diet

Standard Low Carbohydrate Diet

EXPERIMENTAL

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.

Behavioral: Dietary Intervention Standard Low Carbohydrate Diet

Low Fat, Healthy Carbohydrate Diet

EXPERIMENTAL

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.

Behavioral: Dietary Intervention Standard Low Fat Diet

Interventions

Dietary Intervention Mediterranean Low Carbohydrate Diet BEHAVIORAL

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.

Mediterranean Low Carbohydrate Diet

Dietary Intervention Standard Low Carbohydrate Diet BEHAVIORAL

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.

Standard Low Carbohydrate Diet

Dietary Intervention Standard Low Fat Diet BEHAVIORAL

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.

Low Fat, Healthy Carbohydrate Diet

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Prediabetic State; Insulin Resistance; Obesity; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Tracey McLaughlin, MD

  Stanford University, Department of Medicine, Division of Endocrinology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ekrem M Ayhan, BS

CONTACT

908-619-5381; ayhane@stanford.edu

Dalia Perelman, MS, RD

CONTACT

daliap@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: December 21, 2021
• Study Start: January 31, 2019
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)