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

Conditions studied

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

About this study

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.

Interventions

• 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.

Primary outcomes

• Change from baseline on the 2-stage Steady State Plasma Glucose test (Peak weight (4 weeks))
• Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio (Peak weight (4 weeks))
• Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition (Peak weight (4 weeks))
• Change from peak weight on the 2-stage Steady State Plasma Glucose test (Post-weight loss (8 weeks))
• Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio (Post-weight loss (8 weeks))
• Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition (Post-weight loss (8 weeks))
• Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA (Baseline)
• Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay (Baseline)

Eligibility information

Study locations

• Stanford University, Stanford, California 94305 United States