Periodic Report Summary - DIAMARK (Sensory and biomechanical markers in diabetic neuropathy of the gut. Basic investigations and new approaches for treatment) The Diamark project aims at identifying new biomarkers for the stage of autonomic neuropathy to predict the effect of gastric pacing in diabetic patients. The first phase of the project has been focused on development and validation of methods. New probes have been developed to deliver painful mechanical, thermal and electrical stimulations stimuli in the oesophagus. The probes were tested in a series of pilot experiments and the most reliable and robust method was chosen. Furthermore, methods for biomechanical assessment were also evaluated, by use of different phasic and tonic stimuli. In parallel with the probe development comprehensive work has been done to evaluate the brain-gut axis with different imaging and neurophysiologic methods. Recording techniques for a 128-channel EEG system was optimised and algorithms for inverse modelling and classification of EEG traces were successfully implemented. Finally analysis methods have been developed to combine the different outcomes with multivariate statistics. To validate the methods two series of experiments have been completed. The first experiment was a pilot study in 15 healthy volunteers and 16 type-1 diabetic patients with verified autonomic neuropathy and related gastrointestinal symptoms. This study showed the methods to be robust and reliable and showed no differences in EEG traces for different blood sugar levels in diabetic patients. The second series of experiments included 15 pilot studies in healthy volunteers to develop the final probe construction and to validate the comprehensive experimental set-up. The protocol has until now been completed in 10 healthy volunteers and initiated in 7 diabetic patients. Due to logistics patients will be gathered in groups for electrical pacing, which will improve the consistency of the surgical procedure. Therefore patients will be completed in parallel with enrolment of additional patients. The new studies are planned during summer and fall 2010 in Denmark, Sweden and Hungary. In conclusion we believe that the studies will follow the timelines originally planned, although we have had some delay due to difficulties with probe design.