title: Effect of Peripheral Electrical Stimulation (PES) on Nocturnal Blood Glucose in Type 2 Diabetes: A Randomized Crossover Pilot Study.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  We found that during the active period, the most significant effect was on nocturnal glucose control (P < 0.0004), as well as on pre-meal mean glucose levels (P < 0.02). The mean daily glucose levels were also decreased although it did not reach clinical significance (P = 0.07). A reduction in serum cortisol (P < 0.01) but not in insulin was also detected after 2 weeks of treatment. No adverse events were recorded.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02727790.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Catalogna
authors.affiliation: Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Doenyas-Barak
authors.affiliation: Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Roi
authors.initials: R
authors.lastname: Sagi
authors.affiliation: Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ramzia
authors.initials: R
authors.lastname: Abu-Hamad
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Nevo
authors.affiliation: School of Physics and Astronomy, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eshel
authors.initials: E
authors.lastname: Ben-Jacob
authors.affiliation: Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000628:therapy*; D004599:Electric Stimulation Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006854:Hydrocortisone