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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
110
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.
Stanford University
Stanford, California, United States
RECRUITINGChange from baseline on the 2-stage Steady State Plasma Glucose test
Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Peak Weight (4 weeks)
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