Insulin Resistance, Treatment Resistant Essential Hypertension
Conditions
Brief summary
Renal sympathetic nerves contribute to development of hypertension. Sympathetic overactivity also induces insulin resistance and it could therefore be assumed that a renal denervation might improve insulin sensitivity. Studies have shown that glucose metabolism is improved in patients with treatment resistant essential hypertension both 1 and 3 months after renal denervation compared to a control group with treatment resistant essential hypertension. Fasting glucose, insulin and C-peptide decreased significantly as did insulin resistance assessed by HOMA-IR. The investigators wish to investigate the effect of renal denervation on insulin sensitivity using the gold standard - the hyperinsulinemic euglycemic clamp and to investigate the degree of insulin resistance in muscle, liver and adipose tissue.
Interventions
PROCEDURERenal denervation
The patients are examined prior to and 6 months after renal denervation. On the day of examination the patients will have blood samples taken and the hyperinsulinemic euglycemic clamp and muscle and adipose tissue biopsies will be performed.
Sponsors
University of Aarhus
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Systolic daytime ambulatory BP at least 145 mmHg and compliance to a minimum of 3 antihypertensive drugs, including a diuretic
Exclusion criteria
* Diabetes * Pregnancy * Non compliance * Heart Failure (NYHA 3-4) * LV ejection fraction \< 50 % * Renal insufficiency (eGFR\<30) * Unstable coronary heart disease * Coronary intervention within 6 months * Myocardial infarction within 6 months * Claudication * Orthostatic syncope within 6 months * Secondary Hypertension * Permanent atrial fibrillation * Significant Heart Valve Disease * Clinically Significant abnormal electrolytes, haemoglobin, Liver enzymes, TSH * Second and third degree heart block * Macroscopic haematuria * Proximal significant coronary stenosis * Renal artery anatomy not suitable for renal artery ablation (Stenosis, small diameter \< 4 mm, length \< 2 cm, multiple renal arteries, severe calcifications)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity expressed as an M-value | 4 hours | To assess insulin sensitivity the hyperinsulinemic euglycemic clamp is used. The patients are given 0.8 mU/kg/min insulin as an infusion for 2 hours and the blood glucose is clamped at 5 mmol/l. For assessment of endogenous glucose production (EGP) during the glucose clamps, a tracer (3-3 H glucose) is added to the glucose infusion. The patients will be examined by the hyperinsulinemic euglycemic clamp prior to the renal denervation and 6 months after. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin signaling | 6 months | Two biopsies from the lateral vastus muscle and two biopsies from the abdominal subcutaneous adipose tissue are obtained under local anesthesia. Biopsies are taken at baseline and during the clamp. Protein expression involved in the insulin signalling cascade is assessed using standard western blotting techniques. |
Countries
Denmark
Outcome results
None listed