Insulin Resistance, Insulin Sensitivity, Type 2 Diabetes Mellitus
Conditions
Keywords
Gut Microbiota, High Fat Diets, Probiotics, Glycaemic Control
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTYakult light
A fermented milk drink containing the probiotic Lactobacillus casei Shirota
Sponsors
Yakult Honsha Co., LTD
Loughborough University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Participants will be given a unique identifier, which will not disclose the treatment group. All biological samples will be labelled with only the unique identifier.
Intervention model description
Open label, control trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole body insulin sensitivity index | The change between pre- and post-high fat diet (assessed on days 21 and 28) | Assessed by oral glucose tolerance test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting plasma glucose concentration | Day 0, Day 21 and Day 28 | Measured in fasting plasma sample. |
| Fasting serum insulin concentration | Day 0, Day 21 and Day 28 | Measured in fasting serum sample. |
| Fasting plasma triglyceride concentration | Day 0, Day 21 and Day 28 | Measured in fasting plasma sample. |
| Body Mass Index | Day 0, Day 21 and Day 28 | Calculated from height and weight. |
| Markers of systemic inflammation | Day 0, Day 21 and Day 28 | Selected plasma cytokines and chemokines |
| Incretin response to glucose ingestion | Day 0, Day 21 and Day 28 | GLP-1 |
| Microbiome analysis | Day 0, Day 21 and Day 28 | Faecal DNA analysis of the gut microbiota |
| Metabolic endotoxaemia | Day 0, Day 21 and Day 28 | Plasma markers of endotoxaemia |
Countries
United Kingdom
Outcome results
None listed