Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study

Abstract

BackgroundImpaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure.MethodsIn this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc).Results100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients receiving taVNS significantly differed in measures of FPG (F(2) = 10.62, p < 0.001), 2hPG F(2) = 25.18, p < 0.001) and HbAlc (F(1) = 12.79, p = 0.001) over the course of the 12 week treatment period.ConclusionsOur study suggests that taVNS is a promising, simple, and cost-effective treatment for IGT/ pre-diabetes with only slight risk of mild side-effects.

Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study

“…All treatments were applied with an ear vagus nerve stimulator developed through the cooperation of the Institute of Acupuncture and Moxibustion, China Academy to Chinese Medicine Science (Beijing, China) and Suzhou Medical Appliance Factory (Jiangsu Province, China) with special ear clips (electrodes) (Huang et al, 2014; Rong et al, 2014b; Rong et al, 2012). Patients took a seated position or lay on their sides.…”

“…Similar to previous studies (Rong et al, 2014b; Rong et al, 2012), stimulation parameters included: 1) a 20 Hz continuous sinusoidal wave (wave width of 0.2 ms) (Aihua et al, 2014; He et al, 2013; La Marca et al, 2010; Wang et al, 2012), and 2) stimulation intensity increased gradually (starting from 0) to the highest point that the patients could tolerate (typically between 4–6 mA). Each treatment lasted for 30 minutes and was carried out twice a day (once in the morning, once after dinner) (Huang et al, 2014). …”

“…Consequently, direct stimulation of the afferent nerve fibers on the ear should produce an effect similar to classic VNS in reducing depressive symptoms, but without the burden of surgical intervention (Hein et al, 2013; Rong et al, 2012). In past years, taVNS has been applied to treat disorders such as epilepsy (Rong et al, 2014a; Stefan et al, 2012) and pre-diabetes (Huang et al, 2014) and has also been applied to boost associative memory in older individuals (Jacobs et al, 2015). …”

A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder

“…The treatment procedure of sham tVNS was the same as real tVNS except that the stimulation points for sham tVNS were located at the superior scapha (outer ear margin midpoint) where there is no vagus nerve distribution [26,27] (Figure 1, B). …”

Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder

“…Thus, direct stimulation of the afferent nerve fibers on the ear should produce an effect similar to classic VNS in reducing depressive symptoms, but without the burden of surgical intervention (10-11). In past years, tVNS has been applied to treat MDD (10) and other disorders such as epilepsy (12-13), and pre-diabetes (14). Yet, the underlying mechanism of tVNS remains unclear.…”