Healthy Subjects
Conditions
Keywords
Incretins, KATP channels, intradermal injection
Brief summary
This study aims to examine the involvement of KATP channels on the microvascular actions of the incretin GLP-1 and its analogues in healthy individuals and to determine whether the acute oral administration of different KATP channel blockers which are oral medications for Type 2 diabetes such as Glibenclamide and Glimepiride differentially modulate the microvascular responses in these individuals.
Detailed description
In addition to the glucose lowering effect, incretin based therapies have also an effect on the vascular system. Previous animal work and initial human studies suggest that incretins may be cardioprotective and act as vasodilators through opening of KATP channels. Initial evidence suggests that beneficial vascular effects of incretin modifying agents may be nullified by the co-current treatment of the sulfonylurea (SU) drug glibenclamide. The investigators hypothesis is that the GLP-1 and SUs may have conflicting effects on the KATP channels and thus vascular function. Interestingly the vascular actions of GLP-1 were not modified by a different treatment SUs called glimepiride, thereby raising the possibility that SUs differentially modulating the vascular actions of GLP-1 though this remains controversial.
Interventions
OTHERIntradermal injections of GLP-1 and its analogues
native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms
Sponsors
University of Exeter
Katarina Kos
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI ≤ 25 kg/m2
Exclusion criteria
* current or past history of diabetes (HbA1C more or equal 45mmol/mol) * history of postprandial hypoglycaemia and dumping syndrome * established cardiovascular disease * established cerebrovascular disease * blood pressure ≥ 140/85 mmHg * Raynaud's disease * severe impairment of renalhepatic, thyroid or adrenocortical function * current treatment with any anti-hypertensive treatment * lipid lowering therapy or systemic steroids * lactation, pregnancy * established vascular disease * bariatric surgery * significant weight change within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in skin blood flow to GLP-1 and its analogues | 6 weeks | Skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo |
Countries
United Kingdom
Outcome results
None listed