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

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.

Change from baseline on the 2-stage Steady State Plasma Glucose test

Time frame: Peak weight (4 weeks)

Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention

Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio

Time frame: Peak weight (4 weeks)

Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention

Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition

Time frame: Peak weight (4 weeks)

Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention

Change from peak weight on the 2-stage Steady State Plasma Glucose test

Time frame: Post-weight loss (8 weeks)

Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention

Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio

Time frame: Post-weight loss (8 weeks)

Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention

Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition

Time frame: Post-weight loss (8 weeks)

Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention

Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA

Time frame: Baseline

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.

Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay

Time frame: Baseline

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.

Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay

Time frame: Peak Weight (4 weeks)

Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

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Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.