Type 2 Diabetes
Conditions
Keywords
GLP-1 analogues, microvascular, inflammation, fat tissue, clot structure
Brief summary
Some gut hormones, called incretins, stimulate insulin production in order to control sugar levels but also activate brain centres and signal to stop eating. Current administration of incretin-based therapies mimicking these gut hormones is by subcutaneous (just under the skin) injection and has been routinely available for diabetic patients for more than 4 years. It is an effective treatment for the lowering of blood glucose with an average weight loss of about 3-4kg.Recent evidence, from animal studies and limited human studies, suggests that incretins based treatments may also have beneficial effects on blood vessel function. However, it is not known whether this effect is by direct action on the blood vessel independent of an improvement of latent inflammation which is typically associated with weight loss or an anti-inflammatory effect of the incretin treatment itself. The aim of this study is to determine whether the incretin-based diabetes treatment with the GLP-1 (Glucagon-like peptide 1) analogue Liraglutide (also known as Victoza), which mimics the actions of incretins, improves blood vessel function in individuals with type 2 diabetes. It will determine whether the improvement in blood vessel function is independent of the effect of weight loss and changes in inflammation. This by the study of vascular function before and after 4 months of Victoza treatment in subjects with Type 2 diabetes in comparison with 1) participants randomized to hypo-caloric diet to achieve a similar weight loss than with Victoza and 2) participants randomized to treatment with once daily aspirin. Comprehensive assessment of blood vessel function, body fat distribution and metabolic profile at baseline and at the end of the treatment phase will be combined with assessments of inflammation markers in blood and in fat tissue biopsies.
Interventions
DRUGLiraglutide
Administered once daily
OTHERdiet
reduction of caloric intake to promote weight loss
DRUGAspirin
300mg of Aspirin per day
Sponsors
University of Exeter
Royal Devon and Exeter NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes and an HbA1C between 7-8.5% on a stable dose of sulphonylurea and/or metformin
Exclusion criteria
* use of insulin * corticosteroids * contraceptives, tamoxifen * methotrexate * DPP-IV inhibitors * pregnancy * lactation * endocrine disorders * acute MI or cerebrovascular disease * Raynaud's disease or connective tissue disease * current or previous history of malignancy * subjects treated with ergotamine derivatives * unstable blood pressure for the last 3 months * current treatment with warfarin * subjects on any anti-inflammatory or anti-platelet agents * history of any bleeding disorders and GI bleeds.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change of baseline skin maximum hyperaemia at 4 months | baseline and 4 months | laser doppler fluximetry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change of baseline peripheral arterial tone at 4 months | baseline and 4 months | ITAMAR |
| change of baseline endothelial-dependent vasodilation at 4 months | baseline and 4 months | iontophoresis |
| change of baseline capillary density at 4 months | baseline and 4 months | capillaroscopy |
Other
| Measure | Time frame | Description |
|---|---|---|
| change of baseline clot structure at 4 months | baseline and 4 months | rigidity and elasticity of clot structure |
| change of baseline adipose tissue inflammation at 4 months | baseline and 4 months | adipose tissue biopsies will be analysed for gene expression and protein content of inflammatory cytokines |
Countries
United Kingdom
Outcome results
None listed