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Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension: A Pilot Study
Study Questions:
Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to each. What is the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension?
Methods:
Fifty patients with therapy-resistant hypertension were enrolled. Eligibility included the following: >18 years of age, glomerular filtration rate ≥45 ml/min/1.72 m2, office blood pressure of ≥160 mm Hg (≥150 mm Hg for patients with type 2 diabetes mellitus) despite being treated with at least three antihypertensive drugs (including one diuretic), with no changes in medication for a minimum of 2 weeks before enrollment. Thirty-seven patients underwent bilateral catheter-based renal artery denervation using radiofrequency ablation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A1c, 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.
Results:
Mean age was 59.7 ± 1.4 years, 40% were type 2 diabetics, and 74% were male. Patients were taking 5.6 ± 0.2 antihypertensive drugs: 100% a diuretic; 94% an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, or both; 88% beta-blockers; 72% calcium channel blockers; 68% centrally acting sympatholytic agents; and 28% aldosterone antagonists. Mean office blood pressure at baseline was 178/96 ± 3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by −28/−10 mm Hg (p < 0.001) and −32/−12 mm Hg (p < 0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118 ± 3.4 to 108 ± 3.8 mg/dl (p = 0.039). Insulin levels were decreased from 20.8 ± 3.0 to 9.3 ± 2.5 µIU/ml (p = 0.006) and C-peptide levels from 5.3 ± 0.6 to 3.0 ± 0.9 ng/ml (p = 0.002). After 3 months, homeostasis model assessment–insulin resistance decreased from 6.0 ± 0.9 to 2.4 ± 0.8 (p = 0.001). Mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dl (p = 0.012). 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 significantly reducing blood pressure 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.
Perspective:
Previous investigators have demonstrated that reflex sympathetic activation induces acute insulin resistance in the human forearm. They posited that insulin resistance and the metabolic syndrome may result from the heightened sympathetic output found in hypertension resulting in a decrease in microvascular flow to skeletal muscle. That radiofrequency ablation of renal sympathetics reduces central sympathetic outflow lends support to this concept.
Keywords: Insulin, Sympatholytics, Sympathetic Nervous System, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Glomerular Filtration Rate, Homeostasis, Insulin Resistance, Hypertension, Diabetes Mellitus, Glucose
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