Significance: We are in the midst of an epidemic of type 2 diabetes and the closely related metabolic syndrome. These disorders come from a complete interaction between genes and environment which is not fully understood. The goals of this meeting are to address important new areas of research into the primary pathogenesis of these disorders and especially focus on those that might lead to new therapies. The major topics of the meeting are: Mechanisms of metabolic dysfunction and new therapeutic targets for diabetes and obesity; miRNAs in control of metabolism; Aging, mitochondria, and control of metabolism; Epigenetics and perinatal imprinting in diabetes and obesity; CNS control of metabolism; Gastric bypass surgery and the gut in control of metabolism; Metabolic mediators of insulin resistance; and Signaling defects and inflammation in insulin resistance. The major goals of this meeting are to: 1) Make investigators of aware of important new advances in the field of diabetes research. 2) Bring new topics of research from outside the field to the diabetes research community. 3) Stimulate interactions and potential collaborations between participants. 4) Bring lessons from clinical practice back to the bench. We believe we have identified a program which will bring new scientific knowledge, new methods and new insights from clinical practice together to stimulate interchange of ideas and even collaborations. Although this meeting has been a regular annual event in the Keystone Symposium series, many of the topics and speakers are new and thus will enrich the field in new ways. Innovation: The Diabetes Keystone Symposium remains the most important forum for new basic science presentations in the field of diabetes. By bringing it together with the conference on Adipocyte Biology and have multiple joint sessions, we feel this meeting fill a need in the scientific community that is not filled by other conferences. The meeting has novel content that will inform and challenge the attendees and brings many new research paradigms, as well as novel approaches and methods to this scientific community. The meeting is truly interdisciplinary, with not only basic scientists and clinical scientists, it also includes many disciplines outside the fields of endocrinology and metabolism, including gastroenterology, neuroscience, innate immunity, and genetics.