10.1371/journal.pone.0168805 Merav Catalogna Merav Catalogna Keren Doenyas-Barak Keren Doenyas-Barak Roi Sagi Roi Sagi Ramzia Abu-Hamad Ramzia Abu-Hamad Uri Nevo Uri Nevo Eshel Ben-Jacob Eshel Ben-Jacob Shai Efrati Shai Efrati Effect of Peripheral Electrical Stimulation (PES) on Nocturnal Blood Glucose in Type 2 Diabetes: A Randomized Crossover Pilot Study Public Library of Science 2016 glucose levels no-intervention control periods Type 2 Diabetes antidiabetic drug development type 2 diabetes hepatic glucose production PES Peripheral Electrical Stimulation Randomized Crossover Pilot Study Background Regulation T 2DM Methods hepatic insulin sensitivity hypothalamic-pituitary-adrenal axis modulation glucose meter readings Nocturnal Blood Glucose blood glucose control NCT 2016-12-20 21:20:51 Dataset https://plos.figshare.com/articles/dataset/Effect_of_Peripheral_Electrical_Stimulation_PES_on_Nocturnal_Blood_Glucose_in_Type_2_Diabetes_A_Randomized_Crossover_Pilot_Study/4486766 <div><p>Background</p><p>Regulation 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).</p><p>Methods</p><p>Twelve 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.</p><p>Results</p><p>We found that during the active period, the most significant effect was on nocturnal glucose control (<i>P</i> < 0.0004), as well as on pre-meal mean glucose levels (<i>P</i> < 0.02). The mean daily glucose levels were also decreased although it did not reach clinical significance (<i>P</i> = 0.07). A reduction in serum cortisol (<i>P</i> < 0.01) but not in insulin was also detected after 2 weeks of treatment. No adverse events were recorded.</p><p>Conclusions</p><p>These 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.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02727790" target="_blank">NCT02727790</a></p></div>