Type 2 diabetes is a worldwide disease reaching epidemic dimensions. The rapid progressionof the disease urgently calls for both a broader and deeper understanding of its pathophysi-ology. In line with this statement, the Human Diabetes Proteome Project (HDPP) was officiallylaunched at the 11th HUPO meeting in Boston, 2012. A special session was dedicated to thisnew initiative, gathering experts in the main topics related to diabetes and its associatedcomplications. Key issues were debated with a focus on how deranged circulating glucoseand free fatty acids induce dysfunction. It has been decided that HDPP will therefore focus onstudying the early stages of diabetes that lead to abnormal glucose and lipid levels. The ini-tiative will initially focused on islets of Langerhans, insulin-producing cell lines, and bloodhuman samples from diabetes-related cohorts. In subsequent stages HDPP will investigatetarget tissues in which glucose and lipids could promote protein dysfunctions. Omics-rootedsystems approaches enhanced by bioinformatics will be deployed to unravel effects of lipidsand glucose triggering diabetes initiation and progression. A first milestone has been defined