Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
Stanford University
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.
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 wei…
Eligibility
- Age range
- 35–65 years
- Sex
- All
- Healthy volunteers
- Yes
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
Interventions
- BehavioralDietary 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.
- BehavioralDietary 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.
- BehavioralDietary 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.
Location
- Stanford UniversityStanford, California