Renal denervation improves blood pressure, but also insulin and glucose metabolism

Mahfoud F, Schlaich M, Kindermann I et al.
Circulation. 2011;123:1940-1946

Background

Sympathetic overactivity induces insulin resistance, while hyperinsulinemia produces sympathetic activation, thus yielding a vicious cycle [1]. Renal sympathetic afferent and efferent activity can be reduced by a percutaneous, catheter-based approach applying intra-arterial radiofrequency energy, thus treating drug-resistant hypertension. It also reduces muscle sympathetic nerve activity and renal an total body noradrenaline spillover [2-4].
Since the sympathetic nervous system is involved in metabolic control, reduction of its activity might have a substantial effect on glucose metabolism in hypertensive patients. This pilot study aimed to evaluate the relation between sympathetic activity and glucose metabolism and the effect of therapeutic renal denervation in patients with resistant hypertension.  All patients remained on baseline antihypertensive medication. 37 were assigned to the treatment group following protocols of ongoing therapeutic renal denervation trials, whereas 13 control individuals would undergo renal denervation 6 months later. Follow-up was up to 3 months.

Main results

• Renal denervation significantly reduced systolic (-28.+2 mmHg, P<0.001) and diastolic (-10+2 mmHg, P<0.001) blood pressure at 1 month after the procedure. These reductions persisted until the 3-month follow-up (-32 +4 for SBP, -12+2 for DBP respectively, P<0.001). Control subjects did not show a significant change in blood pressure from baseline sitting office systolic (178+2.7) and diastolic (96+2.2) BP.
• Fasting glucose levels were significantly reduced after treatment, from 118+3.4 to 108+3.8 mg/dL (P=0.039), while no changes were seen in the control group. Insulin levels decreased from 20.8+3.0 to 9.3+2.5 µIU/mL (P=0.006), which was associated with reduced C-peptide levels (5.3+0.6 to 3.0+0.9 ng/mL, P=0.002).
• Insulin sensitivity increased significantly after renal denervation (HOMA-IR reduction from 6.0+0.9 to 2.4+0.8, P=0.001, and IS_QUICKI increased from 0.32+0.01 to 0.36+0.01, P=0.001).
• No significant changes in glucose or insulin metabolism were seen during follow-up in the control group..
• During an oral glucose tolerance test (OGTT) after 3 months, glucose levels were significantly reduced after 120 minutes (-27+10.1 mg/dL, P=0.012) in the treatment but not in the control group.  

Conclusion

This study identifies the renal sympathetic nervous system as an important regulator of insulin resistance. Ablation of the renal nerve can substantially improve insulin sensitivity and glucose metabolism, in addition to reducing blood pressure. Thus, selective denervation of the renal sympathetic nerves can improve glucose metabolism and blood pressure control simultaneously in patients with resistant hypertension.

References

1. Mancia G, Bousquet P, Elghozi JL et al. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007;25:909 –920.
2.. Krum H, Schlaich M, Whitbourn R et al. Catheter-based Mahfoud et al Renal Denervation Improves Glucose Metabolism 1945 renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–1281.
3.. Krum H, Sobotka P, Mahfoud F, et al. Device-based antihypertensive therapy: therapeutic modulation of the
autonomic nervous system. Circulation. 2011;123:209 –215.
4. Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomised controlled trial. Lancet. 2010;376:1903–1909.

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