Insulin Resistance, Metabolic Syndrome, Obesity
Conditions
Keywords
Glycaemic Control, Gut Permeability, Gut Microbiota, Metabolic Endotoxemia, Metabolic Health
Brief summary
In the UK, 25% of the adults are affected by metabolic syndrome (NHS, 2016). Metabolic syndrome is a cluster of different conditions including: hyperglycaemia, insulin resistance hypertriglyceridemia, dyslipidaemia and hypertension. Such individuals also have increased risk of developing type 2 diabetes and cardiovascular disease. The factors contributing to the development of metabolic syndrome are potentially numerous and understudied in humans, with much of what we think we know coming from animal research. Recent animal studies have pointed towards gut health playing a role in metabolic health. More specifically it has been suggested that changes in the composition of the gut microbiota may drive insulin resistance and type 2 diabetes through a mechanism that is linked to increased gut permeability and the development of metabolic endotoxemia and inflammation. Yet, this link has not been confirmed in humans. This research will look at the relationship between diet, physical activity, sleeping patterns, obesity status and age etc. and measures of gut bacterial composition, gut barrier function and metabolic health. Findings will provide us with new insights on the effect of different physiological and behavioural/ lifestyle variables on gut health and metabolic function.
Interventions
None listed
Sponsors
University of Reading
Loughborough University
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women aged 18-70 years * BMI 18.5-50 kg/m2 * Not taking antibiotics and antimicrobial drugs for at least three months * Both physically active and sedentary individuals will be eligible to take part in the study * Weight stable (±5kg) for at least 6 months Excusion Criteria: * No cardiometabolic (e.g. heart disease, high blood pressure) or inflammatory illness * Smokers (including the use of vaporisers and e-cigarettes) * Taking anti-inflammatory drugs (excluding aspirin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycaemic control / Whole body insulin sensitivity index | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed by oral glucose tolerance test |
| Systemic Markers of Metabolic Endotoxemia (for example LBP determined using an ELISA) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Serum Lipid Profile (for example total, HDL and LDL cholesterol, TAG, free fatty acids measured by spectrophotometric assay) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples |
| Systemic Markers of Inflammation (for example IL-6, CRP determined using an ELISA/ spectrophotometric assay) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples |
| Systemic Markers of Oxidative Stress (for example protein carbonyls, glutathione and redox enzymes by ELISA/ spectrophotometric assay (in sub-cohort of participants not taking high-dose antioxidant supplements) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples |
| Fasting hormone concentration (for example ghrelin, leptin measured by ELISA) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples |
| Characterisation of immune cell migratory capacity using an ex vivo model (in a sub-cohort of obese participants only) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples by flow cytometry analysis |
| Characterisation of immune cell populations (monocyte subsets) from peripheral blood mononuclear cells | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed following the collection of fasted blood samples by flow cytometry analysis |
| Dietary intake | Cross-sectional (all outcome measures will be collected within a 4 week period) | Assessed via a Food Frequency Questionnaire (FFQ) |
| Fasting blood pressure | Cross-sectional (all outcome measures will be collected within a 4 week period) | Systolic and diastolic blood pressure and central blood pressure, measured in triplicate using a Mobil-O-Graph following 20 min period of seated rest |
| Gut permeability | Cross-sectional (all outcome measures will be collected within a 4 week period) | Urine samples will be used to assess the ratio of lactulose to mannitol excretion |
| Step count | Cross-sectional (all outcome measures will be collected within a 4 week period) | Habitual daily step count as measured by pedometer for 7 consecutive days prior to the first experimental session |
| Self-reported activity | Cross-sectional (all outcome measures will be collected within a 4 week period) | Participants will complete the International Physical Activity Questionnaire to measure participants' time spent in physical activity. |
| Sleeping pattern | Cross-sectional (all outcome measures will be collected within a 4 week period) | Habitual sleep pattern will be assessed by sleep diary 7 consecutive days prior to the first experimental session |
| Functional tests | Cross-sectional (all outcome measures will be collected within a 4 week period) | To be assessed by handgrip strength (measured in force) and timed sit-to-stand movements (measured as time in seconds to perform 5 sit-to-stand movements followed by the maximum number of movements that can be completed in 60 seconds) |
| Questionnaires | Cross-sectional (all outcome measures will be collected within a 4 week period) | Morningness and Eveningness questionnaire; Mood state |
| Urinary metabolomics | Cross-sectional (all outcome measures will be collected within a 4 week period) | Urine samples will be used for metabolic profiling of excreted metabolites |
| Microbiome analysis | Cross-sectional (all outcome measures will be collected within a 4 week period) | Faecal samples will be used to analyse gut microbiota composition through the 16S ribosomal RNA gene sequencing technique |
| Fasting arterial stiffness | Cross-sectional (all outcome measures will be collected within a 4 week period) | Pulse wave analysis and velocity, measured in triplicate using a Mobil-O-Graph following 20 min period of seated rest |
| Anthropometric Measurements (for example height and weight that will be aggregated to report BMI in kg/m^2) | Cross-sectional (all outcome measures will be collected within a 4 week period) | Measured using standard equipment |
Countries
United Kingdom
Contacts
Primary ContactCarl Hulston, PhD
Backup ContactMalvina Begalli, MSc
Outcome results
None listed