As the epidemic of diabetes continues to rise, it becomes essential to develop and implement cost-effective preventative therapeutic strategies . In this study, We compared the efficacy of taVNS and sham taVNS in patients with IGT. Results showed that compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance. In addition, we found that taVNS significantly decreased systolic blood pressure over time (F(1) = 4.21, p = 0.044) as compared with controls who received no treatment. Taken together, our results suggest that taVNS demonstrates potential use as a preventive treatment for pre-diabetes or IGT.
The metabolic syndrome, which includes a constellation of risk factors such as obesity, elevated lipids, and elevated glucose and blood pressure, has increasingly drawn attention from investigators; this syndrome is regarded as both a disease and a risk factor for other major diseases such as cardiovascular disease and Alzheimer’s disease (AD) . These diseases not only harm our well-being and longevity, but also have a tremendous economic impact . Prevention and treatment of these disorders require a considerable number of medical resources. The discovery of a simple and cost-effective method of controlling these disorders may significantly benefit society.
Previous studies have suggested that the vagus nerve plays an important role in maintaining metabolic homeostasis. These studies further suggest that efferent vagus nerve-mediated cholinergic signaling controls immune function and proinflammatory responses via the inflammatory reflex. Deregulation of metabolism and immune function are associated with chronic inflammation, which acts as a critical step in the pathogenesis of insulin resistance and type 2 diabetes mellitus [9, 16].
In a previous study, investigators  found that metabolic syndrome had an independent inverse association with the vagal component of high-frequency heart rate variability. In another study, Licht and colleagues  found that decreased parasympathetic and increased sympathetic activities are associated with increased likelihood of metabolic syndrome. Specifically, they found that lower respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity in which high RSA reflects high parasympathetic activity, was associated with glucose levels and systolic blood pressure. Taken together, these studies suggest that low vagus nerve activity may underlie elevated glucose levels, which provides the biological mechanism of modulating IGT using taVNS.
Anatomical studies have shown that the ear is the only place on the surface of the human body where there is afferent vagus nerve distribution (12; 13). Thus, direct stimulation of the afferent nerve fibers on the ear can regulate the activity of the vagus nerve, which can further regulate metabolic homeostasis. In this study, we found that taVNS reduced both IGT and systolic blood pressure. This result suggests that taVNS has the potential for use as a therapeutic method for IGT and pre-diabetes, as well as potentially for other metabolic syndromes.
In this study, we found that both taVNS and sham taVNS significantly reduced the 2-hour glucose tolerance and levels of HbAlc, indicating that sham taVNS could also produce a significant, and desirable, modulatory effect on glucose levels. We speculate that this may be due to the strong electrical stimulation at the sham point extending to the adjacent area of the ear, where there is vagus nerve distribution. In addition, sham taVNS may produce these placebo effects by influencing patient lifestyle. Patients were asked to apply the postprandial treatment twice daily, which might have reminded them to pay more attention to food intake and levels of daily activity.
There are several limitations in this study. First, treatments in the study were self-administered by the patients, and thus patient compliance may have influenced the observed results. To enhance compliance, all patients were required to complete daily entries into a diary that was checked during assessments. More importantly, however, this self-administration method provides direct evidence for the feasibility of wide application of the method used within the study. This shows promise in significantly reducing the expenses associated with such a treatment. Secondly, the treatment was only 12 weeks in duration, thus the results obtained only represent its short or mid-term effects. Further study is warranted to evaluate the long-term effects of this treatment option. Thirdly, we only measured blood glucose level at three time points (the baseline, after 6 weeks, and after 12 weeks) for statistic analysis. Since blood glucose levels may be affected by the food intake of the previous day, a more frequent measurement in the future study may provide more reliable information for the influence of treatment on blood glucose level. Finally, the no-treatment control group was not included in the randomization scheme, as were the other two treatment groups. The participants constituting the control group were also recruited from a different population. However, the purpose of this group was to add another layer of control to explore the effects of the different treatments; thus, it should not influence the conclusions of this study.