This proposal from Wake Forest University is to continue as a Clinical Center in the Gastoparesis Clinical Research Consortium (GpCRC) and to continue our excellent follow up and retention of the 105 patients we have thus far recruited to the Registry. In addition, we will continue enrollment into the Registry and complete three treatment trials (NORIG, GLUMIT-DG, APRON). We will also utilize the resources of the Consortium and the Registry to continue to investigate the etiology, epidemiology, and morbidity and mortality associated with gastroparesis. Our center will support the Pathological Basis of Gastroparesis Study conducted by Dr. Farrugia at the Mayo Clinic in Rochester, MN for identification of the molecular factors involved in pathogenesis of gastroparesis as we institute a program of gastric stimulator therapy. The goal of the GpCRC sponsored by the NIDDK since 2006 is to focus on the etiology, treatment strategies, and clinical course of gastroparesis and we will continue to support the Consortium and Data Coordinating Center (DCC) in designing and carrying out the protocols, providing data in a timely manner to the DCC, developing publication priorities, and creating abstracts and manuscripts for publication. Our site will continue to participate fully in all Coordinator and Steering Committee activities. We will also continue to work efficiently with the NIDDK Biosample, Genetic and Data Repositories. Patients with Type 2 diabetes mellitus (T2DM) develop gastroparesis and associated symptoms. Our site specific proposal is to investigate gastric motility and neuro-endocrinological abnormalities in patients with Type 2 diabetes. We hypothesize that these neuro-endocrine defects affect;a) myoelectrical and contractile properties of the stomach and, b) the release of gut hormones which control insulin secretions and hunger and satiety (GLP-1, GIP, ghrelin, VIP and NPY) in a differential manner over time. We propose to investigate the gastric neuromuscular and the endocrinologic reponses to a mixed meal in individuals ranging from pre-diabetes to late Type 2 diabetes (>10 years since diagnosis). PUBLIC HEALTH RELEVANCE: Gastroparesis Consortium's research so far underscores the public health significance of gastroparesis including the need to understand the natural history of gastroparesis, develop effective methods for management of gastroparesis identify patients at risk for progression to more severe gastroparesis and to identify the key cellular changes that lead to gastroparesis.