AUTHOR=Faber Jens , Eldrup Ebbe , Selmer Christian , Pichat Caroline , Hecquet Sofie Korsgaard , Watt Torquil , Kreiner Svend , Karpatschof Benny , Gyntelberg Finn , Ballegaard Søren , Gjedde Albert TITLE=Reduction of Pressure Pain Sensitivity as Novel Non-pharmacological Therapeutic Approach to Type 2 Diabetes: A Randomized Trial JOURNAL=Frontiers in Neuroscience VOLUME=Volume 15 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.613858 DOI=10.3389/fnins.2021.613858 ISSN=1662-453X ABSTRACT=Autonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects the tradition. The present study focused on the role of cerebral regulation of ANSD as a novel understanding of glucose metabolism and treatment target in type 2 diabetes (T2D), based on the observation that the pressure pain sensitivity (PPS) of the chest bone periosteum can be interpreted as a measure of cerebral ANSD. In patients with ischemic heart disease a recent study demonstrated that mortality was lowered by a home-based non-pharmacological treatment, using PPS as a behavioral guide for stress, and repeated sensory nerve stimulation for reducing PPS. In a randomized controlled trial of 144 patients with T2D, we tested if six months of this treatment reduced PPS, and improved glucose metabolism In the active treatment group, mean glycated hemoglobin A1c (HbA1c) declined from 53.8 mmol/mol to 50.5 (intra-group p = 0.001), compared to the change from 53.8 to 53.4 mmol/mol in the control group (between-group p = 0.036). Mean PPS declined from 76.6 to 56.1 units (p < 0.001) in the active treatment group, and from 77.5 to 72.8 in the control group (p = 0.02; between group p < 0.001). Changes of PPS and HbA1c were correlated (r = 0.37; p < 0.001). We conclude that the proposed approach to treatment of T2D is a potential alternative or supplement to conventional therapy.