Effect of vagus nerve stimulation on blood glucose concentration in epilepsy patients – Importance of stimulation parameters

In previous animal experiments, we demonstrated that cervical vagus nerve stimulation (VNS) inhibits pancreatic insulin secretion, thereby raises blood glucose levels, and impairs glucose tolerance through afferent signaling. However, there are no reports suggesting that similar effects occur in patients treated with chronic cervical VNS for epilepsy. In contrast to clinical VNS used for epilepsy, where the stimulation is intermittent with cycles of on and off periods, stimulation was continuous in our previous animal experiments. Thus, we hypothesized that the timing of the stimulation on/off cycles is critical to prevent impaired glucose tolerance in epilepsy patients chronically treated with cervical VNS. We conducted a retrospective analysis of medical records from patients with epilepsy. Blood glucose levels did not differ between patients treated with pharmacotherapy only (98 ± 4 mg/dL, n = 16) and patients treated with VNS plus pharmacotherapy (99 ± 3 mg/dL, n = 24, duration of VNS 4.5 ± 0.5 years). However, a multiple linear correlation analysis of patients with VNS demonstrated that during the follow‐up period of 7.9 ± 0.7 years, blood glucose levels increased in patients with long on and short off periods, whereas blood glucose did not change or even decreased in patients that were stimulated with short on and long off periods. We conclude that chronic cervical VNS in patients with epilepsy is unlikely to induce glucose intolerance or hyperglycemia with commonly used stimulation parameters. However, stimulation on times of longer than 25 sec may bear a risk for hyperglycemia, especially if the stimulation off time is shorter than 200 sec.