Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension A Pilot Study
ABSTRACT 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.
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 178/96±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). Additionally, 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.
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.
URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.
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ABSTRACT: Chronic elevation of sympathetic nervous system is a key factor in metabolic syndrome. Because renal denervation (RDN) is thought to modulate sympathetic activity, we performed the Denervation of the Renal Arteries in Metabolic Syndrome (DREAMS)-study to investigate the effects of RDN on insulin sensitivity and blood pressure (BP) in patients with metabolic syndrome. Twenty-nine patients fulfilling the criteria for metabolic syndrome and who used a maximum of 1 antihypertensive or 1 antidiabetic drug or 1 of both gave informed consent and were treated by RDN. Glucose tolerance tests and 24-hour ambulatory BP measurements were performed at baseline, at 6 and 12 months of follow-up. Moreover, we performed self-monitored BP measurements at home every month. To assess sympathetic activity, we performed muscle sympathetic nerve activity and heart rate variability measurements at baseline and follow-up. The majority of the included patients was men (57%), mean body mass index was 31±5 kg/m(2). Median insulin sensitivity as assessed by the Simple Index assessing Insulin Sensitivity oral glucose tolerance test did not change at 6- and 12-month follow-up (P=0.60 and P=0.77, respectively). Mean 24-hour BP decreased by 6±12/5±7 mm Hg 12 months after RDN (P=0.04/0.01). However, self-monitored BP measurements data showed no reduction over time. Measurements of sympathetic activity showed no reduction in systemic sympathetic activity. In conclusion, RDN did not lead to a significant improvement of insulin sensitivity ≤12 months after treatment. Although a significant reduction in ambulatory BP was observed in this nearly drug-naïve population, the self-monitored BP measurements data suggest that this may be explained by regression to the mean. Moreover, no effect in systemic sympathetic activity was observed. © 2015 American Heart Association, Inc.Hypertension 02/2015; 65(4). DOI:10.1161/HYPERTENSIONAHA.114.04798 · 7.63 Impact Factor
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ABSTRACT: The renal autonomic nervous system may contribute to hypertension and vascular disease. Although the effects of renal artery denervation on blood pressure lowering are controversial, there may be other beneficial vascular effects independent of blood pressure lowering. Bilateral renal denervation (RDN) or sham operation (SO) was performed in 14-week-old male apolipoprotein E-deficient mice on a Western diet starting at 10 weeks of age. Efficacy of RDN was confirmed by reduction of renal norepinephrine levels (SO: 3.8±0.1 versus RDN: 1.7±0.3 ng/mL; P<0.01) at 6 weeks after procedure. Compared with SO, RDN had no effect on blood pressure (SO: 101.0±2.4 versus RDN: 97.5±1.6 mm Hg; P=0.25), total cholesterol (SO: 536.7±28.5 versus RDN: 535.7±62.9 mg/dL; P=0.99), or triglycerides (SO: 83.7±3.5 versus RDN: 86.9±10.2 mg/dL; P=0.78). Quantification of atherosclerosis at 20 weeks of age demonstrated reduced atherosclerosis in mice receiving RDN compared with SO (arterial tree oil-red-O surface staining RDN: 4.2±0.5% versus SO: 6.3±0.7%; P<0.05). Reduced atherosclerosis was associated with increased smooth muscle cell content in atherosclerotic plaques (RDN: 13.3±2.1 versus SO: 8.1±0.6%; P<0.05). Serum levels of aldosterone, monocyte chemoattractant protein-1, and 8-isoprostane were lower in mice that received RDN compared with sham-operated mice (aldosterone; RDN: 206.8±33.2 versus SO: 405.5±59.4 pg/mL, P<0.05; monocyte chemoattractant protein-1; RDN: 51.7±7.9 versus SO: 91.71±4.6 pg/mL, P<0.05; 8-isoprostane; RDN: 331.9±38.2 versus SO: 468.5±42.0 pg/mL, P<0.05). RDN reduces progression of atherosclerosis in apolipoprotein E-deficient mice. These changes are associated with reduced aldosterone levels, monocyte chemoattractant protein-1, and markers of oxidative stress. © 2015 American Heart Association, Inc.Hypertension 02/2015; 65(4). DOI:10.1161/HYPERTENSIONAHA.114.04648 · 7.63 Impact Factor
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ABSTRACT: Insulin resistance (IR) is a general phenomenon of many physiological states, disease states, and diseases. IR has been described in diabetes mellitus, obesity, infection, sepsis, trauma, painful states such as postoperative pain and migraine, schizophrenia, major depression, chronic mental stress, and others. In arthritis, abnormalities of glucose homeostasis were described in 1920; and in 1950 combined glucose and insulin tests unmistakably demonstrated IR. The phenomenon is now described in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, polymyalgia rheumatica, and others. In chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin sensitivity. This paper delineates that IR is either based on inflammatory factors (activation of the immune/ repair system) or on the brain (mental activation via stress axes). Due to the selfishness of the immune system and the selfishness of the brain, both can induce IR independent of each other. Consequently, the immune system can block the brain (for example, by sickness behavior) and the brain can block the immune system (for example, stress-induced immune system alterations). Based on considerations of evolutionary medicine, it is discussed that obesity per se is not a disease. Obesity-related IR depends on provoking factors from either the immune system or the brain. Chronic inflammation and/or stress axis activation are thus needed for obesity-related IR. Due to redundant pathways in stimulating IR, a simple one factor-neutralizing strategy might help in chronic inflammatory diseases (inflammation is the key), but not in obesity-related IR. The new considerations towards IR are interrelated to the published theories of IR (thrifty genotype, thrifty phenotype, and others).Arthritis Research & Therapy 01/2014; 16 Suppl 2:S4. DOI:10.1186/ar4688 · 4.12 Impact Factor