Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension

Abstract

Background-Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results-We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A 1c , calculated insulin sensitivity (homeostasis model assessment-insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96Ϯ3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by Ϫ28/Ϫ10 mm Hg (PϽ0.001) and Ϫ32/Ϫ12 mm Hg (PϽ0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118Ϯ3.4 to 108Ϯ3.8 mg/dL (Pϭ0.039). Insulin levels were decreased from 20.8Ϯ3.0 to 9.3Ϯ2.5 IU/mL (Pϭ0.006) and C-peptide levels from 5.3Ϯ0.6 to 3.0Ϯ0.9 ng/mL (Pϭ0.002). After 3 months, homeostasis model assessment-insulin resistance decreased from 6.0Ϯ0.9 to 2.4Ϯ0.8 (Pϭ0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (Pϭ0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions-Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.

Renal Denervation: Unde Venis et Quo Vadis?

“…In addition to the blood pressure reduction, an improvement of the hyperinsulinism and insulin resistance present in metabolic syndrome seems to occur: 3 months after renal denervation the fasting glucose level (118 ± 3.4 vs. 108 ± 3.8 mg/dL), the insulin level (20.8 ± 3.0 vs. 9.3 ± 2.5 μIU/mL) and the (calculated HOMA) insulin resistance decreased significantly [59]. However, these study populations were relatively small collective and not fully randomized [59,60].…”

“…In addition to the blood pressure reduction, an improvement of the hyperinsulinism and insulin resistance present in metabolic syndrome seems to occur: 3 months after renal denervation the fasting glucose level (118 ± 3.4 vs. 108 ± 3.8 mg/dL), the insulin level (20.8 ± 3.0 vs. 9.3 ± 2.5 μIU/mL) and the (calculated HOMA) insulin resistance decreased significantly [59]. However, these study populations were relatively small collective and not fully randomized [59,60]. Also a decrease of left ventricular hypertrophy (decrease in left ventricular mass index 6.3 ± 2.2 to 9.6 ± 1.9 g/m 2.7 ) and an improvement in the left ventricular diastolic function were described [61] even though this study also has methodological weaknesses (including a lack of data regarding changes in antihypertensive medication in the follow-up period, echocardiography instead of the gold standard of cardiac MRI for determining the left ventricular mass) [62].…”

Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel on Renal Sympathetic Denervation

“…Subgroup analysis and phase II testing have also shown improvements in other diseases associated with autonomic dysfunction, such as sleep apnea, insulin-resistant diabetes, left ventricular (LV) hypertrophy, tachyarrhythmias, and congestive heart failure (CHF) (13,16). Ongoing RDN clinical trials for the treatment of resistant HTN continue this trend of investigating other potential benefits associated with RDN.…”

“…Denervation can also increase venous compliance, leading to increased capacity, which may alleviate the blood pooling in the peripharyngeal tissues. Better BP control can also contribute to apnea improvement through its influence on baroreflex reactivity and central respiratory control (13,16). RDN in patients with resistant HTN and OSA might attenuate the effects of activation of the sympathetic nerves.…”

“…Additional findings from mostly small, uncontrolled, observational studies have suggested numerous favorable cardiovascular responses to RDN that are in need of corroboration (11)(12)(13)(14)(15)(16). The potential for early clinical adoption has also driven the development and clinical testing of multiple new devices for ablation of the perirenal sympathetic nerve fibers (17,18).…”