Dietary Intervention Modifies Gut Microbiota in Type 2 Diabetes.

A Dietary Intervention With Functional Foods Reduce Metabolic Endotoxemia and Attenuates Biochemical Abnormalities in Subjects With Type 2 Diabetes by Modifying the Gut Microbiota.

Aim: To study the effect of a dietary intervention with functional foods on gut microbiota in subjects with type 2 diabetes Materials and methods: Patients with type 2 diabetes were enrolled in a double-blind, parallel-arm, placebo-control study were randomized to receive a dietary portfolio (DP) or placebo (P) treatment for 3 mo. The primary endpoint was the effect of a dietary portfolio based on functional foods on gut microbiota. Secondary endpoints were biochemical parameters, branched chain amino acids, TMAO

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: dietary portfolio

Detailed Description

This study was a single-center, randomized, controlled, double-blind, parallel versus placebo that consisted of six visits. The first visit was a screening evaluation to determine whether subjects meet the inclusion criteria. The selected subjects were invited to a second visit that consisted of a medical history, 2-h oral glucose tolerance test (OGTT), collection of stool samples for DNA isolation and collection of 5 ml blood sample. The participants received the first stage dietary strategy for 15 days. In the third visit and second stage of dietary treatment, subjects were randomized to received the dietary portfolio (DP) or placebo (P) treatment accompanied of the reduced energy diet for 1 mo. In the fourth and fifth visits, with a 1 mo interval, dietary assessment and compliance to the DP or P was evaluated. During each follow-up visit, a 24-h dietary recall was collected, a physical activity questionnaire was filled out and anthropometric and clinical parameters were assessed. In the sixth visit, a 2-h oral glucose tolerance test (OGTT) was performed, and a stool sample for DNA isolation and 5 ml blood were collected.

Dietary Intervention In the first stage, the participants consumed a reduced-energy diet tailored to provide a 500-kcal/d deficit as recommended by NIH (8) the with respect to their habitual diet for 15 days. The diet plan consisted in 45-55% carbohydrates, 15-20% protein, 25-35% fat, <7% saturated fat, 200 mg/d cholesterol, 20-35g fiber, 2000-3000 mg/d sodium based on total energy. In the second stage the participants continued to consume the reduced energy diet with the addition of a combination of functional foods (dietary portfolio; DP). The DP provided 200 kcal that were subtracted from the diet. The DP consisted of a mixture of 14g of dehydrated nopal, 4g of chia seed, 30g of soy protein, 4g of inulin,) and 1g of flavoring. The placebo (P) consisted of 28 g of calcium caseinate, 15g of maltodextrin and 1g of flavoring. The kcal, appearance and flavor were similar in DP and P. The DP and P was given in a package in dehydrated form ready to be dissolved in water. The DP was divided into two packages, the first package contained 17.3 g of DP or P given in the breakfast and dissolved in 250 ml and the second package was given at the dinner time (15:00-16:00 h) and contained 34.7g of P and DP dissolved in 300 mL of water.

Dietary compliance Dietary compliance was assessed with a 24-h dietary recall and 3-d food record (food log), during each visit that were analyzed by Food Processor Nutrition Analysis Software. The compliance of the consumption of the DP or P was evaluated with the number of empty packages returned at the following visit. Physical activity was assessed using the International physical activity questionnaire (IPAQ).

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis of type 2 diabetes
• Male or female.
• Adults between 30 and 60 years old.
• BMI of 25 to 39.9 kg / m².
• Pharmacological treatment with metformin, a combination of metformin and glibenclamide.
• Evolution of the type 2 diabetes of 4 ± 3 years.
• Patients who knew how to read and write.
• Signature of informed consent.

Exclusion Criteria:

• Diseases that produce secondary obesity.
• Cardiovascular event.
• Weight loss> 3 kg in the last 3 months after the evaluation of the criteria.
• Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
• Gravidity status.
• Positive smoking.
• Treatment with antihypertensive drugs
• Treatment with other hypoglycemic agents that were not metformin
• Treatment with statins, fibrates or other drugs to control dyslipidemia, 6 months before the start of the protocol.
• Any drug or medication that activates intestinal motility
• Use of laxatives or antispasmodics 4 weeks before the study
• Treatment with antibiotics 6 months before the study
• Use of steroids, chemotherapy, immunosuppressant or radiotherapy.
• Uncontrolled type 2 diabetes, ( HbA1c concentration ≥ 9.9%)
• Fasting glucose ≥ 220 mg / dL
• Fasting cholesterol ≥ 240 mg / dL
• Fasting triglycerides ≥ 350 mg / dL
• Serum creatinine in women> 1.2 mg / dL in men> 1.3 mg / d

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. Dietary portfolio (DP); the dietary portfolio was given daily in the breakfast and dinner for 2.5 months	Dietary supplement: dietary portfolio; The dietary intervention was a combination of functional foods (dehydrated nopal, chia seed, soy protein and inulin) that was provided in dehydrated form in packages of 17.3 g dissolved in 250 ml water for breakfast and 34.7 g in 300 ml water for dinner.
Placebo Comparator: 2. placebo (P); the placebo (P) was based was given daily in the breakfast and dinner for 2.5 months	Dietary supplement: dietary portfolio; The dietary intervention was a combination of functional foods (dehydrated nopal, chia seed, soy protein and inulin) that was provided in dehydrated form in packages of 17.3 g dissolved in 250 ml water for breakfast and 34.7 g in 300 ml water for dinner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intestinal microbiota	Measurement of intestinal microbiota by sequencing using the Illumina platform	Change from baseline gut microbiota at three months after the dietary intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose metabolism profile	serum glucose (mg/dl)	Change from baseline serum glucose at three months after dietary intervention
Glucose metabolism profile	serum insulin (µUI/ml)	Change from baseline serum insulin at three months after dietary intervention
Glucose metabolism profile	plasma glycated hemoglobin (HbA1c) (%)	Change from baseline plasma HbA1c at three months after dietary intervention
Lipid metabolism profile	serum triglycerides (mg/dl)	Change from baseline serum triglycerides at three months after dietary intervention
Lipid metabolism profile	serum total cholesterol (mg/dl)	Change from baseline serum total cholesterol at three months after dietary intervention
Lipid metabolism profile	serum LDL cholesterol (mg/dl)	Change from baseline serum LDL cholesterol at three months after dietary intervention
Lipid metabolism profile	serum HDL cholesterol (mg/dl)	Change from baseline serum HDL cholesterol at three months after dietary intervention
Lipid metabolism profile	plasma free fatty acids (FFA) (mmol/L)	Change from baseline plasma free fatty acids at three months after dietary intervention
metabolomic profile	plasma betaine (µmol/L)	Change from baseline plasma betaine at three months after dietary intervention
metabolomic profile	plasma choline (µmol/L)	Change from baseline plasma choline at three months after dietary intervention
metabolomic profile	plasma trimethylamine oxide (TMAO) (µmol/L)	Change from baseline plasma TMAO at three months after dietary intervention
metabolomic profile	plasma branched chain amino acids (BCAA) (µmol/L)	Change from baseline plasma BCAA at three months after dietary intervention
inflammatory profile	plasma lipopolysaccharide (LPS) (ng/ml)	Change from baseline plasma LPS at three months after dietary intervention
inflammatory profile	serum C reactive protein (CRP) (mg/dl)	Change from baseline serum CRP at three months after dietary intervention

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborators: University of Connecticut
• Investigators: Principal Investigator: Nimbe Torres, PhD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

General Publications

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• Serralde-Zuniga AE, Guevara-Cruz M, Tovar AR, Herrera-Hernandez MF, Noriega LG, Granados O, Torres N. Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans. Genes Nutr. 2014 Nov;9(6):431. doi: 10.1007/s12263-014-0431-5. Epub 2014 Sep 27.
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Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2014
• Primary Completion (Actual): September 28, 2016
• Study Completion (Actual): December 28, 2016

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 29, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: type 2 diabetes; gut microbiota; TMAO; branched chain amino acids; functional foods
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 1165

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No