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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.

Besides the known effect on blood pressure, our study showed for the first time that RD significantly reduces LV mass and improves diastolic function, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk.

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