Effect of Peripheral Electrical Stimulation (PES) on Nocturnal Blood Glucose in Type 2 Diabetes: A Randomized Crossover Pilot Study

BackgroundRegulation of hepatic glucose production has been a target for antidiabetic drug development, due to its major contribution to glucose homeostasis. Previous pre-clinical study demonstrated that peripheral electrical stimulation (PES) may stimulate glucose utilization and improve hepatic insulin sensitivity. The aim of the present study was to evaluate safety, tolerability, and the glucose-lowering effect of this approach in patients with type 2 diabetes (T2DM).MethodsTwelve patients with T2DM were recruited for an open label, interventional, randomized trial. Eleven patients underwent, in a crossover design, an active, and a no-intervention control periods, separated with a two-week washout phase. During the active period, the patients received a daily lower extremity PES treatment (1.33Hz/16Hz burst mode), for 14 days. Study endpoints included changes in glucose levels, number of hypoglycemic episodes, and other potential side effects. Endpoints were analyzed based on continuous glucose meter readings, and laboratory evaluation.ResultsWe found that during the active period, the most significant effect was on nocturnal glucose control (P P P = 0.07). A reduction in serum cortisol (P ConclusionsThese results indicate that repeated PES treatment, even for a very short duration, can improve blood glucose control, possibly by suppressing hepatic glucose production. This effect may be mediated via hypothalamic-pituitary-adrenal axis modulation.Trial registrationClinicalTrials.gov NCT02727790背景 鉴于肝脏葡萄糖生成对葡萄糖稳态具有核心调控作用，其始终是抗糖尿病药物研发的关键靶点。既往临床前研究证实，外周电刺激（peripheral electrical stimulation, PES）可促进葡萄糖利用，并改善肝脏胰岛素敏感性。本研究旨在评估该疗法应用于2型糖尿病（T2DM）患者的安全性、耐受性及降糖效果。 方法 本研究招募12名T2DM患者，开展一项开放标签、干预性随机试验。其中11名患者采用交叉设计，分别接受活性干预阶段与无干预对照阶段，两阶段之间设置为期2周的洗脱期。活性干预期内，患者每日接受下肢外周电刺激治疗（1.33Hz/16Hz脉冲爆发模式），持续14天。研究终点包括血糖水平变化、低血糖发作次数及其他潜在不良反应。终点指标通过持续葡萄糖监测读数与实验室检测进行分析。 结果 研究发现，在活性干预阶段，该疗法对夜间血糖控制的改善效果最为显著（P P P = 0.07）。血清皮质醇水平降低（P 结论 上述结果表明，即便疗程极短，重复外周电刺激治疗即可改善血糖控制，其潜在机制可能为抑制肝脏葡萄糖生成。该效应可能通过调节下丘脑-垂体-肾上腺轴实现。 试验注册 ClinicalTrials.gov 注册号：NCT02727790