NCT05165706

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 110 (estimated)
• Sponsor: Stanford University · Academic / Other
• Sex: All
• Age: 35 Years – 65 Years
• Healthy volunteers: Accepted

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.

Conditions

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

Interventions

Type	Name	Description
BEHAVIORAL	Dietary Intervention Mediterranean Low Carbohydrate Diet	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 Standard Low Carbohydrate Diet	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 Fat Diet	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.

Timeline

• Start date: 2019-01-31
• Primary completion: 2026-11-30
• Completion: 2026-12-30
• First posted: 2021-12-21
• Last updated: 2024-12-04

Locations

1 site across 1 country: United States