Clinical trial NCT06961279: Resveratrol Stimulates Insulin Sensitivity in Subjects With Obesity and Insulin Resistance
Official title: Resveratrol Stimulates Insulin Sensitivity, and Changes Microbiota Taxonomy and Serum Metabolomics in Participants With Obesity and Insulin Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2025-05-07
Enrollment: 38
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is evidence that resveratrol can improve insulin resistance in rodents and humans with obesity and it can also improve muscle mitochondrial content mediated through activation of AMPK. However, little is known if this improvement is associated with changes in the gut microbiota and how gut microbiota is associated with serum metabolites after consumption of resveratrol. In the present study, the investigators show that the consumption of resveratrol for 2 months could influence insulin sensitivity in subjects with obesity. This effect will be accompanied by a modification of the microbiota taxonomy and the metabolites derived from this. Consequently, there will be a reduction in metabolic endotoxemia accompanied by an increase in AMP-activated protein kinase (AMPK) phosphorylation and the expression of genes of mitochondrial biogenesis in skeletal muscle.

Detailed description: The investigators included 38 participants who met the following inclusion criteria: adults between 20 and 60 years of age with a diagnosis of HOMA-IR index greater than 2.5, and BMI ≥30 and ≤ 40 kg / m2 and who signed the consent letter. Participants who had any added pathology, pregnancy, smoking or consumed medications were excluded. Once the letter of informed consent was accepted, the patients were assigned to the respective treatment group. These individuals were advised to consume the recommended diet for subjects with obesity. Participants were randomly distributed to consume a) placebo treatment or b) resveratrol capsules (150 mg/day). The participants were followed for 2 months. In the pre-randomization visit, informed consent letters were given, and blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin, blood pressure, body weight and height and body composition. The presence of insulin resistance was determined by means of the HOMA-IR index. For the first visit body composition, other biochemical parameters such as protein c reactive, alanine transaminase, aspartate transaminase, hemoglobin glycosylated, hormones as leptin and adiponectin, free fatty acids in serum, malondialdehyde in serum, lipopolysaccharide in serum, short chain fatty acids in feces, fecal microbiota and serum metabolomics were determined. After 2 months, the same variables were assessed, and an expert surgeon in the operating room performed a vastus lateralis muscle biopsy, then protein extraction was performed.

Eligibility criteria: Inclusion Criteria:

* Male and female.
* Between 20 and 60 years
* BMI ≥ 30 and ≤ 40 kg/m2
* Presence of insulin resistance (HOMA-IR index ≥ 2.5)
* Willing and able to sign written informed consent prior to trial entry

Exclusion Criteria:

* Patients with any type of diabetes.
* Patients with kidney disease diagnosed by a medical or with creatinine\> 1.3 mg / dL for men and \> 1.1 mg / dL for women and / or BUN\> 20 mg / dL.
* Patients with acquired diseases that produce obesity and diabetes secondarily.
* Patients who have suffered a cardiovascular event.
* Patients with gastrointestinal diseases.
* Weight loss \> 3 kg in the last 3 months.
* Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
* Pregnancy status.
* Antibiotic consumption 3 months prior to the study.
* Be an undergraduate or graduate student within the Institute.
* Positive smoking.
* Drug treatment:

  * Antihypertensive drugs or treatment
  * Treatment with hypoglycemic agents or insulin and antidiabetic drugs.
  * Treatment with statins, fibrates or other drugs to control dyslipidemia.
  * Use of antibiotics in the three months prior to the study.
  * Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.
  * Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.
  * Probiotic, prebiotic or symbiotic supplements.

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Baseline to 2 months
Secondary outcomes:
measure: Fecal microbiota
timeFrame: Baseline to 2 months
measure: Glucose metabolism profile
timeFrame: Baseline to 2 months
measure: Insulin (µUI/ml)
timeFrame: Baseline to 2 months
measure: Triglycerides
timeFrame: Baseline to 2 months
measure: Total cholesterol
timeFrame: Baseline to 2 months
measure: LDL cholesterol
timeFrame: Baseline to 2 months
measure: HDL cholesterol
timeFrame: Baseline to 2 months
measure: Antioxidant profile
timeFrame: Baseline to 2 months
measure: Body weight
timeFrame: Baseline to 2 months
measure: Blood pressure
timeFrame: Baseline to 2 months
measure: Change in PGC1α content
timeFrame: Through study completion, an average of 2 months
measure: Change in AMPK content
timeFrame: Through study completion, an average of 2 months
measure: Succinate dehydrogenase
timeFrame: Through study completion, an average of 2 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
Study officials:
affiliation: INCMNSZ
name: Armando R Tovar, Dr.
role: PRINCIPAL_INVESTIGATOR
References: