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| Name | Class |
|---|---|
| Diabetes UK | OTHER |
| Liverpool University Hospitals NHS Foundation Trust | OTHER_GOV |
| Royal Liverpool University Hospital | OTHER_GOV |
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Study investigates the hypothesis that an exercise programme of steady walking will have larger effects on insulin sensitivity and glycemic control when combined with Acipimox intake prior to each exercise session in people with pre-diabetes. Thirty-four sedentary, overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with pre-diabetes will be recruited using the same strategy as study 2 and split into two groups (detailed below). Participants will undergo several pre- intervention assessments, followed by a 12-week walking based intervention combined with either Acipimox ingestion or no drug ingestion, pre- each exercise session. Following this, the post-assessment measures will identical to the pre-assessment measures.
Study 3 investigates the hypothesis that an exercise programme of steady walking will have larger effects on insulin sensitivity and glycaemic control when combined with Acipimox intake prior to each exercise session in people with prediabetes. Thirty-four sedentary, overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with prediabetes will be recruited using the same strategy as study 2 and split into two groups (detailed below).
Pre-intervention assessments:
Visit 1: Participants will undergo an assessment of body composition (DXA) and undertake a graded treadmill walking test to estimate maximal aerobic fitness (VO2max).
Visit 2: Participants will be able to opt to undergo an MRI scan, taking place before breakfast. The MRI scan is used to measure fat stored in the liver and muscles. A continuous glucose monitoring (CGM) sensor will be inserted to measure insulin sensitivity.
Visit 3: Participants will arrive at the laboratory after an overnight fast (>10 h) to undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity. Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained from the vastus lateralis muscle of one leg before and after 2 hours of the clamp.
Exercise intervention: Pairs of participants from each group (matched for gender, age and VO2max) will be randomized to undertake 12 weeks of steady walking combined with ingestion of either Acipimox or placebo in a counter-balanced, double-blind design. Supervised treadmill walking sessions will be undertaken at LJMU three times per week, with exercise performed at a speed equivalent to 45% VO2max. Participants will initially exercise for 30 mins per session (weeks 1 and 2), and each session will increase in duration by 5 mins every 2 weeks thereafter, up to 50 minutes of exercise. 1 hour before each walking session, participants will ingest either 250 mg Acipimox or nothing.
Post-intervention assessments: The post-intervention assessments will be identical in all respects to the pre-intervention assessments and will be commenced ≥72 hours after the final training session.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acipimox ingestion | Active Comparator | Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor), muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest 250 mg of Acipimox 1 hour before each exercise session of the 12 week intervention. |
|
| No drug | Placebo Comparator | Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor) with muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest nothing prior to their exercise sessions during the 12-week exercise programme. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise Program | Other | 12-week walking based intervention (3 sessions per week) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity | A pre- and post- hyperinsulinaemic euglycaemic clamp will assess changes in whole body insulin sensitivity. | A change in insulin sensitivity from baseline will be compared to week 12. |
| Measure | Description | Time Frame |
|---|---|---|
| Sub-maximal VO2 walking test | Participants will be assessed for pre- and post- maximal aerobic capacity. | A change in aerobic capacity (VO2) from baseline will be compared to week 12. |
| Percentage of Liver Fat |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer s Barrett, PhD | Liverpool John Moores University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Liverpool John Moores University | Liverpool | Merseyside | L18 8EU | United Kingdom |
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34 pre-diabetics will be split into 2 groups; one will ingest Acipimox for 12-weeks and the other will ingest nothing.
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both participants and investigators will know if they are ingesting Acipimox or nothing.
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| DXA | Diagnostic Test | Participants will undergo an assessment of body composition (DXA) |
|
| MRI | Diagnostic Test | used to measure fat stored in the liver |
|
| Hyperinsulinaemic Euglycaemic Clamp | Diagnostic Test | Participants will arrive at the laboratory after an overnight fast (>10 h) to undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity. Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained from the vastus lateralis muscle of one leg before and after 2 hours of the clamp. |
|
| VO2 Max | Diagnostic Test | Assessment of maximum aerobic capacity. |
|
| Continuous Glucose Monitor | Diagnostic Test | CGM sensor will be inserted to measure insulin sensitivity over a 24hr period. |
|
| Muscle Biopsies | Procedure | Participants will undergo muscle biopsies pre and post the hyperinsulinemic euglyceamic clamp from the vastus lateralis. |
|
| Acipimox 250 MG | Drug | Participants will be randomised into two groups. One group will be prescribed Acipimox that will be taken 1 hour prior to each exercise session. The other group will take no drug. |
|
A pre- and post- intervention MRI scan will show any changes in Liver Fat
| The change percentage of liver fat will be measured at baseline and be compared to value at the end of week 12. |
| Changes in Intramuscular GLUT4 | Muscle biopsy samples will undergo analysis of mechanisms for insulin sensitivity and lipid metabolites using confocal immunofluorescence microscopy. | A change in the co-localisation of GLUT4 will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention. |
| Change in intramuscular DAGs | The amount of DAGs within the muscle will be analysed using liquid chromatography-mass spectrometry. | A change in the amount of DAGs will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention. |
| ID | Term |
|---|---|
| D018149 | Glucose Intolerance |
| ID | Term |
|---|---|
| D006943 | Hyperglycemia |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D055070 | Resistance Training |
| C027696 | acipimox |
| ID | Term |
|---|---|
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
| D005791 | Patient Care |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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