Genistein Stimulates Insulin Sensitivity Through Gut Microbiota

Not Applicable

Completed

• Conditions: Obesity; Metabolic Syndrome
• Interventions: Dietary Supplement: genistein; Dietary Supplement: Placebo

• Registration Number: NCT04105023
• Lead Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Brief Summary

There is evidence that genistein present in soy can improve insulin resistance in rodents and humans with metabolic syndrome (MetS). However, it is not known if this improvement is associated with changes in the gut microbiota. In the present study, the investigators show that the consumption of genistein for 2 months could have an effect on insulin resistance in subjects with MetS. This effect will be accompanied by a modification of the gut microbiota taxonomy. As a consequence, 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 fatty acid oxidation in skeletal muscle.

Detailed Description

The investigators included 45 participants who met the following inclusion criteria: adults between 20 and 60 years of age with a diagnosis of MetS, HOMA index greater than 2.5, BMI ≥30 and ≤ 40 kg / m2 and who signed the consent letter. Patients 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 MetS according to the guidelines of the ATPIII. Participants were randomly distributed to consume a) placebo treatment or b) genistein capsules (50 mg/day). The participants were followed for 2 months. In the previsit, informed consent letters were given, and blood samples were taken to evaluate glucose concentration, lipid profile, lipopolysaccharide and serum insulin. Also determined blood pressure, body weight, height, body composition and gut microbiota. The presence of insulin resistance was determined by means of the HOMA-IR index and by an oral glucose tolerance test. After 2 months, the same variables were assessed, and an expert surgeon in the operating room performed a vastus lateralis muscle biopsy, then RNA extraction and gene expression microarray assay was performed

Study Timeline

• Study Start: 2013-09-15
• Primary Completion: 2017-12-15
• Study Completion: 2018-12-01
• Status Verified: 2019-09
• Study First Submitted: 2019-09-20
• Study First Submitted QC: 2019-09-24
• Last Update Submitted: 2019-09-24
• Study First Posted: 2019-09-26
• Last Update Posted: 2019-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Adults (men and women) between the ages of 18 and 50.
• Patients with obesity (BMI ≥ 30 and ≤ 40 kg / m2) and with insulin resistance (HOMA - IR Index ≥ 2.5).
• Mexican mestizos (parents and grandparents born in Mexico).
• Patients who can read and write.

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 weight loss > 3 kg in the last 3 months.
  • Patients with any catabolic diseases.
  • Gravidity status
  • Positive smoking
  • Treatment with any medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
genistein	genistein	Genistein capsules of 25 mg each, 50mg/day
placebo	Placebo	Maltodextrin capsules, administered orally once every 12 hours

Primary Outcome Measures

Name	Time	Method
intestinal microbiota	Baseline to 2 month	Measurement of gut microbiota by sequencing using the Illumina platform

Secondary Outcome Measures

Name	Time	Method
Triglycerides	Baseline to 2 month	serum triglycerides (mg/dL)
HDL cholesterol	Baseline to 2 month	serum HDL cholesterol (mg/dL)
Total Cholesterol	Baseline to 2 month	serum total cholesterol (mg/dL)
Inflammatory profile	Baseline to 2 month	plasma lipopolysaccharide (LPS) (ng/mL)
Body weight	Baseline to 2 month	body weight (kg)
glucose metabolism profile	Baseline to 2 month	serum glucose (mg/dL)
Glucose metabolism profile	Baseline to 2 month	serum insulin (µUI/ml)
LDL cholesterol	Baseline to 2 month	serum LDL cholesterol (mg/dL)
Blood pressure	Baseline to 2 month	blood pressure (mmHg)