Genistein Stimulates Insulin Sensitivity Through Gut Microbiota

Obesity Clinical Trial

— GENISTEIN  

Official title:

Genistein Stimulates Insulin Sensitivity Through Gut Microbiota Reshaping and Skeletal Muscle AMPK Activation in Obese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04105023
• Other study ID #: 1099
• Status: Completed
• Phase: N/A
• Start date: September 15, 2013
• Est. completion date: December 1, 2018

Study information

• Verified date: September 2019
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 1, 2018
• Est. primary completion date: December 15, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Insulin Resistance
• Metabolic Syndrome
• Obesity

Intervention

Dietary Supplement:
• genistein
Administered orally once every 12 hours
• Placebo
Administered orally once every 12 hours

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	National Council of Science and Technology, Mexico

References & Publications (4)

Guevara-Cruz M, Flores-López AG, Aguilar-López M, Sánchez-Tapia M, Medina-Vera I, Díaz D, Tovar AR, Torres N. Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome. J Am Heart Assoc. 2019 Sep 3;8(17):e012401. doi: 10.1161/JAHA.119.012401. Epub 2019 Aug 27. — View Citation

López P, Sánchez M, Perez-Cruz C, Velázquez-Villegas LA, Syeda T, Aguilar-López M, Rocha-Viggiano AK, Del Carmen Silva-Lucero M, Torre-Villalvazo I, Noriega LG, Torres N, Tovar AR. Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet. Mol Nutr Food Res. 2018 Aug;62(16):e1800313. doi: 10.1002/mnfr.201800313. Epub 2018 Jul 29. — View Citation

Medina-Vera I, Sanchez-Tapia M, Noriega-López L, Granados-Portillo O, Guevara-Cruz M, Flores-López A, Avila-Nava A, Fernández ML, Tovar AR, Torres N. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019 Apr;45(2):122-131. doi: 10.1016/j.diabet.2018.09.004. Epub 2018 Sep 25. — View Citation

Palacios-González B, Vargas-Castillo A, Velázquez-Villegas LA, Vasquez-Reyes S, López P, Noriega LG, Aleman G, Tovar-Palacio C, Torre-Villalvazo I, Yang LJ, Zarain-Herzberg A, Torres N, Tovar AR. Genistein increases the thermogenic program of subcutaneous WAT and increases energy expenditure in mice. J Nutr Biochem. 2019 Jun;68:59-68. doi: 10.1016/j.jnutbio.2019.03.012. Epub 2019 Mar 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	intestinal microbiota	Measurement of gut microbiota by sequencing using the Illumina platform	Baseline to 2 month
Secondary	glucose metabolism profile	serum glucose (mg/dL)	Baseline to 2 month
Secondary	Glucose metabolism profile	serum insulin (µUI/ml)	Baseline to 2 month
Secondary	Triglycerides	serum triglycerides (mg/dL)	Baseline to 2 month
Secondary	Total Cholesterol	serum total cholesterol (mg/dL)	Baseline to 2 month
Secondary	LDL cholesterol	serum LDL cholesterol (mg/dL)	Baseline to 2 month
Secondary	HDL cholesterol	serum HDL cholesterol (mg/dL)	Baseline to 2 month
Secondary	Inflammatory profile	plasma lipopolysaccharide (LPS) (ng/mL)	Baseline to 2 month
Secondary	Body weight	body weight (kg)	Baseline to 2 month
Secondary	Blood pressure	blood pressure (mmHg)	Baseline to 2 month