Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

May, Marcus; Ahrens, Jelka; Menne, Jan; Haller, Hermann; Beige, Joachim; Eckert, Siegfried; Jordan, Jens; Engeli, Stefan

doi:10.2337/db13-1651

Cited by 20 publications

(10 citation statements)

References 21 publications

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“…110 However, in a randomized, double-blind, crossover study of 16 patients with hypertension who were defined as BP responders to baroreflex activation therapy, acute baroreceptor stimulation had no discernible effect on insulin sensitivity. 111 Furthermore, in patients with chronic kidney disease, muscle SNA is increased in proportion to the degree of renal impairment. 59,110,112,113 Sympathetic overactivity, therefore, constitutes a putative therapeutic target to slow progression of chronic kidney disease and its cardiovascular complications.…”

Section: Current and Potential Indicationsmentioning

confidence: 99%

Carotid baroreflex activation therapy for resistant hypertension

Victor

2015

Nat Rev Cardiol

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Arterial baroreceptors are mechanosensitive sensory nerve endings in the walls of the carotid sinuses and aortic arch that buffer the increases and decreases in arterial blood pressure. Electrical field stimulation of the carotid sinus, known as carotid baroreflex activation therapy, holds promise as a novel device-based intervention to supplement, but not replace, drug therapy for patients with resistant hypertension. Acute electrical field stimulation of even one carotid sinus can cause a sufficiently large reflex decrease in blood pressure to overcome offsetting reflexes from the contralateral carotid baroreceptors and aortic baroreceptors that are not paced. However, the initial phase III Rheos Pivotal Trial on continuous carotid baroreceptor pacing for resistant hypertension with the first-generation baroreceptor pacemaker yielded equivocal data on efficacy and adverse effects due to facial nerve injury during surgical implantation. A miniaturized second-generation pacing electrode has seemingly overcome the safety issue, and early results with the new device suggest efficacy of unilateral carotid sinus stimulation in heart failure. A phase III trial of this new device for resistant hypertension has been registered.

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Section: Current and Potential Indicationsmentioning

confidence: 99%

Carotid baroreflex activation therapy for resistant hypertension

Victor

2015

Nat Rev Cardiol

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“…In humans, there is an inverse relationship between insulin sensitivity and whole body NE spillover in obese individuals, and MSNA is higher in those with insulin resistance compared to those who are insulin sensitive 10 . Not all studies, however, have found that sympathetic activity is associated with decreased insulin sensitivity 11, 12 . Furthermore, a direct causal link between the sympathetic nervous system and insulin sensitivity has not been established in obesity.…”

Section: Introductionmentioning

confidence: 99%

Autonomic Blockade Improves Insulin Sensitivity in Obese Subjects

et al. 2014

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Obesity is an important risk factor for the development of insulin resistance. Initial compensatory mechanisms include an increase in insulin levels, which are thought to induce sympathetic activation in an attempt to restore energy balance. We have previously shown, however, that sympathetic activity has no beneficial effect on resting energy expenditure in obesity. On the contrary, we hypothesize that sympathetic activation contributes to insulin resistance. To test this hypothesis, we determined insulin sensitivity using a standard hyperinsulinemic euglycemic clamp protocol in obese subjects randomly assigned in a crossover design one month apart to receive saline (intact day) or trimetaphan (4 mg/min IV, autonomic blocked day). Whole body glucose uptake (MBW in mg/kg/min) was used as index of maximal muscle glucose utilization. During autonomic blockade we clamped blood pressure with a concomitant titrated IV infusion of the nitric oxide synthase inhibitor L-NMMA. Of the 21 obese subjects (43±2 years of age, 35±2 kg/m2 BMI) studied fourteen were insulin resistant; they were more obese, had higher plasma glucose and insulin, and higher muscle sympathetic nerve activity (23.3±1.5 vs. 17.2±2.1 burst/min, p=0.03) compared to insulin sensitive subjects. Glucose utilization improved during autonomic blockade in insulin resistant subjects (MBW 3.8±0.3 blocked vs. 3.1±0.3 mg/kg/min intact; p=0.025), with no effect in the insulin sensitive group. These findings support the concept that sympathetic activation contributes to insulin resistance in obesity and may result in a feedback loop whereby the compensatory increase in insulin levels contributes to greater sympathetic activation.

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“…Confirmation of these findings in properly controlled clinical trials is mandatory [37•]. In an acute study by our group, electrical carotid sinus stimulation did not improve glucose metabolism assessed by frequently sampled intravenous glucose tolerance testing [38].…”

Section: Evidence For Organ Protection?mentioning

confidence: 69%

Electrical Carotid Sinus Stimulation: Chances and Challenges in the Management of Treatment Resistant Arterial Hypertension

Chobanyan-Jürgens

Jordan

2015

Curr Hypertens Rep

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Treatment resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term blood pressure control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced blood pressure in a controlled clinical trial but nevertheless failed to meet the primary efficacy endpoint. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in blood pressure with the second-generation device. We hope that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Meanwhile, we should find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation.

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Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

Cited by 20 publications

References 21 publications

Carotid baroreflex activation therapy for resistant hypertension

Carotid baroreflex activation therapy for resistant hypertension

Autonomic Blockade Improves Insulin Sensitivity in Obese Subjects

Electrical Carotid Sinus Stimulation: Chances and Challenges in the Management of Treatment Resistant Arterial Hypertension

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