| dc.contributor.advisor | Steigen, Terje | |
| dc.contributor.author | Miroslawska, Atena | |
| dc.date.accessioned | 2021-06-08T07:49:08Z | |
| dc.date.available | 2021-06-08T07:49:08Z | |
| dc.date.issued | 2021-06-23 | |
| dc.description.abstract | <p>Background: Denervation of renal sympathetic nerves (RDN) is a mini-invasive endovascular procedure introduced as an antihypertensive treatment with a potentially beneficial effect on insulin resistance. In this open-label non-randomized study we investigated non-diabetic patients with true treatment-resistant hypertension defined as office systolic blood pressure (BP)>140 mmHg and (mean) daytime (ambulatory) BP >135 mmHg, despite four or more antihypertensive drugs.
<p>Methods: Bilateral RDN was performed with the Symplicity Catheter System (N=23), and patients were followed- for six and 24 months. BP measurements were performed after witnessed intake of antihypertensive drugs. BP variability and arterial stiffness indices were calculated from 24-hour BP recordings. Insulin sensitivity was assessed using a two-step hyperinsulinemic- euglycemic clamp with glucose tracer before and six months after RDN. Oral glucose tolerance test, levels of insulin, C-peptide, adiponectin and leptin were measured and surrogate insulin resistance indices were calculated before RDN and during follow-up.
<p>Results: Most of the patients were obese, had metabolic syndrome and severe insulin resistance at baseline. We found a statistically significant reduction of both office and ambulatory 24-hour BP as well as BP variability six months after RDN. Despite decline in BP, neither peripheral nor hepatic insulin sensitivity improved six months after RDN. Twenty patients continued to the two-year follow up. Some rebound in BP was found in most of patients. Arterial stiffness did not change during follow-up. All measured metabolic variables and insulin resistance surrogate indices remained essentially unaltered two years after RDN.
<p>Conclusion: Neither peripheral nor hepatic insulin sensitivity improved after RDN. Our study does not support the notion of a beneficial metabolic effect of RDN in patients with treatment resistant hypertension. | en_US |
| dc.description.doctoraltype | ph.d. | en_US |
| dc.description.popularabstract | In the western world, about 30-40% of adults suffer from too high blood pressure (hypertension). In 1945, when President Roosevelt died of stroke, there were no pills to treat hypertension and surgeons sometimes had to cut the nerves around the kidneys to lower the blood pressure. Although this treatment was performed in more than 1200 cases in the United States until 1953, it was discontinued due to severe surgical complications and the development of medicines that could lower blood pressure. Currently 10 – 20 % of hypertensive patients cannot achieve optimal blood pressure, and have a high risk of stroke or a heart attack, even when taking all the prescribed drugs. For these patients a new and mini-invasive method called renal denervation has been developed in an attempt to turn off the nervous signals sent from the kidneys to the brain, signals that would normally increase blood pressure. These signals run through nerve fibers located in the adventitia (outer layer) of the renal arteries. A thin electric ablation catheter that applies energy (heat) to the vessel wall has been constructed to achieve denervation. With this method, the kidney nerves can be destroyed from inside of the renal vessel, without the need for surgery.
More than 50% of all patients suffering from hypertension are considered to have some degree of insulin resistance (also known as prediabetes). Insulin resistance is a condition during which body cells do not recognize insulin as a key that helps glucose (blood sugar) to enter the cells. This leads to too high glucose concentration in the blood and overproduction of insulin, which subsequently contributes to the increase of blood pressure and development of type 2 diabetes. Some of the previous studies have suggested that renal denervation may end this vicious circle and reduce both high blood pressure and insulin resistance.To confirm these findings a renal denervation study has been conducted at UiT the Arctic University of Norway, selecting only nondiabetic patients who, despite using four or more antihypertensive pills every day, had a very high blood pressure. Because previous studies have shown that many hypertensive patients do not take their medicines as prescribed, in this study compliance to prescription drugs were controlled and non-compliant patients were excluded. The effects of renal denervation on glucose metabolism and blood pressure were examined at 6 and 24 months after the procedure.
Why is this study important?
Previous studies elicited huge enthusiasm, claiming that renal denervation could reduce blood pressure and prevent diabetes, but only simplified methods to assess insulin resistance were used. That is why it was important to seek to confirm these findings using the “gold standard method” called clamp. Clamp is a specialized 6-hour examination, during which every patient gets injected insulin and glucose at the same time and blood samples are taken every 5 minutes to keep blood sugar at a normal level. In this way, one can exactly assess how the tissue responds to insulin. In addition, blood pressure was measured before and after renal denervation.
What have we found?
The results of our study revealed that already before renal denervation, most of our non-diabetic patients suffered from severe insulin resistance. We found that renal denervation did not reduce insulin resistance, neither after short term nor after long term follow-up.
However, we observed a significant decrease in blood pressure after 6 months in about 50 % of patients. There are still unresolved questions, who responds to renal denervation and what is the duration of the effect? We controlled blood pressure 2 years after renal denervation and observed that some of the patients kept the blood pressure reduction, but others did not.
Conclusion: This study could not confirm the previously reported amelioration of glucose metabolism after
renal denervation when using a “gold standard method” for assessing insulin resistance. | en_US |
| dc.description.sponsorship | UIT | en_US |
| dc.identifier.uri | https://hdl.handle.net/10037/21370 | |
| dc.language.iso | eng | en_US |
| dc.publisher | UiT The Arctic University of Norway | en_US |
| dc.publisher | UiT Norges arktiske universitet | en_US |
| dc.relation.haspart | <p>Paper I: Miroslawska, A., Solbu, M., Skjølsvik, E., Toft, I. & Steigen, T.K. (2016). Renal sympathetic denervation: effect on ambulatory blood pressure and blood pressure variability in patients with treatment-resistant hypertension. The Re-Shape CV-risk study. <i>Journal of Human Hypertension, 30</i>(3), 153-157. Also available at <a href=https://doi.org/10.1038/jhh.2015.69>https://doi.org/10.1038/jhh.2015.69</a>.
<p>Paper II: Miroslawska, A.K., Gjessing, P.F., Solbu, M.D., Fuskevåg, O.M., Jenssen, T.G. & Steigen T.K. (2016). Renal Denervation for Resistant Hypertension Fails to Improve Insulin Resistance as Assessed by Hyperinsulinemic-Euglycemic Step Clamp. <i>Diabetes, 65</i>(8), 2164-2168. Reprinted with permission from The American Diabetes Association. Copyright 2016 American Diabetes Association. Also available at <a href=https://doi.org/10.2337/db16-0205>https://doi.org/10.2337/db16-0205</a>.
<p>Paper III: Miroslawska, A.K., Gjessing, P.F., Solbu, M.D., Norvik, J.V., Fuskevåg, O.M., Hanssen, T.A. & Steigen, T.K. (2021). Metabolic effects two years after renal denervation in insulin resistant hypertensive patients. The Re-Shape CV-risk study. <i>Clinical Nutrition, 40</i>(4), 1503-1509. Also available at <a href=https://doi.org/10.1016/j.clnu.2021.02.027>https://doi.org/10.1016/j.clnu.2021.02.027</a>. | en_US |
| dc.rights.accessRights | openAccess | en_US |
| dc.rights.holder | Copyright 2021 The Author(s) | |
| dc.subject.courseID | DOKTOR-003 | |
| dc.subject | VDP::Medical disciplines: 700 | en_US |
| dc.subject | VDP::Medisinske Fag: 700 | en_US |
| dc.title | Renal sympathetic denervation, potential effects on blood pressure and glucose metabolism in patients with severe treatment resistant hypertension. The Re-shape CV-risk study | en_US |
| dc.type | Doctoral thesis | en_US |
| dc.type | Doktorgradsavhandling | en_US |
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