Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans

Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans. A Large-cohort, Mechanistic Follow-up Study.

Participants will be randomly allocated to either Yakult ingestion or a control group. For the first 20 days, subjects will consume their normal diet (keeping a detailed food diary throughout). On days 21-28 they will switch to a high-fat/high-calorie diet.

The investigators hypothesise that consuming a high-fat, high-energy diet for 7 days will alter the composition of the gut microbiota and induce metabolic endotoxaemia / systemic inflammation as well as decreasing whole body insulin sensitivity (as we have shown previously). In contrast, the investigators hypothesise that consuming Yakult for 21 days before and 7 days throughout the high-fat diet will maintain a favourable gut microbiota and prevent metabolic endotoxaemia / systemic inflammation and thus maintain insulin action / insulin sensitivity.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Insulin Resistance; Insulin Sensitivity
• Intervention / Treatment: Dietary supplement: Yakult light

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Leicestershire
    • Loughborough, Leicestershire, United Kingdom, LE11 3TU
      • Loughborough University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 26 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females
• Aged 18-30
• Physically active (exercising at least 3 times per week for more than 30 min at a time)
• Non-smoker
• Free from cardiovascular or metabolic disease
• Weight stable for at least 6 months
• Normal body mass index (BMI: 18.5-24.9 kg/m2)*

• Compliant (i.e. understands and is willing, able and likely to comply with all study requirements)

  • Note: If BMI is >24.9, but body fat % (as measured by bioelectrical impedance analysis) is below 21% in males and 31% in females, then the subject may still be recruited at the PI's discretion.

Exclusion Criteria:

• Using probiotic or prebiotic supplements within the previous 3 months
• Vegetarians and vegans
• Diagnosis of insulin resistance, pre-diabetes or full diabetes
• Underweight (determined as BMI less than 18.5 kg/m2)
• Overweight or obese (determined as BMI greater than 24.9 kg/m2)
• Those on a calorie controlled diet or other dietary restrictions that would prevent them from consuming the probiotic treatment and high fat/high calorie diet.
• Those who are unwilling to restrict their intake of fermented dairy products.
• Those with known or suspected food intolerances, allergies or hypersensitivity
• Women who are known to be pregnant or who are intending to become pregnant over the course of the study.
• Participation in another clinical trial
• Those who have donated blood within 3 months of the screening visit and participants for whom participation in this study would result in having donated more than 1500 ml of blood in the previous 12 months.
• Participants who take any form of regular medication that is known to affect either the gut microbiota and/or insulin sensitivity or who have taken any antibiotics in the previous 3 months.
• Participants who know they would not be available for all the lab visits during the 4-week study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Participants will receive 2 x 65mL doses of Yakult light per day, for 28 days. Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28.	Dietary supplement: Yakult light; A fermented milk drink containing the probiotic Lactobacillus casei Shirota
No Intervention: Control Group; Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole body insulin sensitivity index	Assessed by oral glucose tolerance test.	The change between pre- and post-high fat diet (assessed on days 21 and 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index	Calculated from height and weight.	Day 0, Day 21 and Day 28
Fasting plasma glucose concentration	Measured in fasting plasma sample.	Day 0, Day 21 and Day 28
Fasting serum insulin concentration	Measured in fasting serum sample.	Day 0, Day 21 and Day 28
Fasting plasma triglyceride concentration	Measured in fasting plasma sample.	Day 0, Day 21 and Day 28
Metabolic endotoxaemia	Plasma markers of endotoxaemia	Day 0, Day 21 and Day 28
Markers of systemic inflammation	Selected plasma cytokines and chemokines	Day 0, Day 21 and Day 28
Incretin response to glucose ingestion	GLP-1	Day 0, Day 21 and Day 28
Microbiome analysis	Faecal DNA analysis of the gut microbiota	Day 0, Day 21 and Day 28

Collaborators and Investigators

• Sponsor: Loughborough University
• Collaborators: Yakult Honsha Co., LTD
• Investigators: Principal Investigator: Carl J Hulston, Loughborough University

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2017
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: January 27, 2017
• First Posted (Estimate): January 31, 2017

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Probiotics; Gut Microbiota; Glycaemic Control; High Fat Diets
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: R16-P132

Drug and device information, study documents

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