The pancreas in human type 1 diabetes: providing new answers to age-old questions.
Although studies of pancreata from type 1 diabetes (T1D) patients largely fell dormant for a period of decades, research efforts have recently been 'rekindled' in this area to address, using modern techniques, many unanswered questions related to the pathogenesis of this disease. As historically noted, a pancreatic infiltrate commonly referred to as 'insulitis' is present at the symptomatic onset of T1D. Recent studies have further characterized this infiltrate both in terms of its cellular composition as well as the mechanisms that likely underlie beta cell death in T1D. In addition, the notion that the pancreas from T1D patients is completely devoid of insulin producing cells years after the onset of disease has been challenged, whereas the concepts of whether beta cell regeneration or replication are present have also been subject to much debate. Novel concepts regarding the rate and degree of beta cell loss throughout the natural history of the disease have also been put forward to aid in explaining the disorder's pathogenesis. Although answers to many long-standing questions in T1D have recently been addressed, perhaps the main finding has been one supporting a disease of remarkable heterogeneity. However, additional lessons remain to be learned from the pancreas in T1D. Hence, attempts aimed at organizing the scientific community to address these issues are ongoing, particularly those from collaborative efforts, including the Belgium Organ Donor Consortium and the Network for Pancreatic Organ Donors with Diabetes (nPOD).DOI: 10.1097/MED.0b013e32832e06ba