Type 1 diabetes (T1D) is considered chronic autoimmune disease in which autoreactive T-cells and inflammation cause severe loss of pancreatic beta cells. Insulitis, the pathologic hallmark of T1D, is an inflammatory lesion consisting of immune cell infiltrates around and within the islets. New research initiatives and methodologies are advancing our understanding of pancreas pathology. A major impetus to the field has been given by the institution of the JDRF nPOD (Network for the Pancreatic Organ donor with Diabetes, www.JDRFnPOD.org); nPOD recovers and provides pancreata from organ donors with T1D to the scientific community and facilitates collaborative studies about the pathogenesis and pathology of T1D. Studies by several nPOD investigators have revealed the predominant cellular types that infiltrate the islets, novel molecular aspects associated with insulitis, and the coexistence of additional pathological abnormalities. While insulitis is a critical element of T1D pathogenesis, it is present only in a modest proportion of islets at any given time, even at diagnosis, with overall limited relation to disease duration. Thus, the relative importance of insulitis as a determining factor of diabetes symptoms at diagnosis may be overestimated; at the same time, growing evidence shows that beta cell loss at diagnosis is more modest than previously thought, and co-existing beta cell dysfunction may be a key contributor to insulin deficiency at diagnosis. This recognition has relevance for the design of clinical trials, as targeting the immune system only may have limited therapeutic efficacy. Combination therapies that promote both immunoregulation and address beta cell dysfunction should be more effective in treating this chronic disease process. It remains a major goal to clarify the relation of insulitis with the dynamics of beta cell loss and coexisting mechanisms of dysfunction, according to clinical stage; such improved understanding is key to design therapeutic strategies that target multiple pathogenic mechanisms.
10 Sep 2016 - 12 Sep 2016