Type 2 diabetes is a worldwide disease reaching epidemic dimensions. The rapid progression of the disease urgently calls for both a broader and deeper understanding of its pathophysiology. In line with this statement, the Human Diabetes Proteome Project (HDPP) was officially launched at the 11th HUPO meeting in Boston, 2012. A special session was dedicated to this new initiative, gathering experts in the main topics related to diabetes and its associated complications. Key issues were debated with a focus on how deranged circulating glucose and free fatty acids induce dysfunction. It has been decided that HDPP will therefore focus on studying the early stages of diabetes that lead to abnormal glucose and lipid levels. The initiative will initially focused on islets of Langerhans, insulin-producing cell lines, and blood human samples from diabetes-related cohorts. In subsequent stages HDPP will investigate target tissues in which glucose and lipids could promote protein dysfunctions. Omics-rooted systems approaches enhanced by bioinformatics will be deployed to unravel effects of lipids and glucose triggering diabetes initiation and progression. A first milestone has been defined for the 12th HUPO meeting in Yokohama, 2013: the 1000 diabetes-associated protein (the 1000-HDPP) database, i.e. a freely available internet resource (www.HDPP.info) of more than 1000 proteins with links to their corresponding proteotypic peptides, affinity reagents and protein-specific biological/biomedical information. Human islets digested and seperated by off-gel electrophoresis. Analysis by LTQ-Orbitrap velos mass spectrometer (fragmentation by CID,gaz phase fractionnation with four m/z windows: 400-520, 515-690, 685-979, 974-2000)