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Synopses of Research Articles Death by Necrosis: The Early Stages of Type 1 Diabetes DOI: 10.1371/journal.pmed.0030051 Diabetes mellitus is a major global health problem. The most common form of diabetes—90%–95% of cases—is type 2 or non-insulin-dependent diabetes, which affects mainly adults. The remaining cases are type 1 or insulin-dependent diabetes. Also known as juvenile diabetes, type 1 diabetes usually develops before the age of 30. It is an autoimmune disease in which the insulin-producing orβ-cells of chromatin-binding protein that is released by cells undergoing necrosis but not apoptosis) by ratβ-cells. Finally, because humanβ-cells behave somewhat differently from ratβ-cells, the researchers demonstrate that a combination of cytokines (including IL-1) stimulated HMGB1 release from some preparations of human islets in an NO- dependent manner. Overall, the authors conclude that macrophage-derived cytokines may participate in the early stages of type 1 diabetes by inducing necrotic death in β-cells. Other researchers believe that apoptotic cell death is more important in these early stages, particularly in human cells. But, based on their results, Corbett and colleagues speculate that cytokine induction of necrosis could kick start type 1 diabetes by causing the release of bothβ-cell antigens and HMGB1, which stimulates in?ammatory responses. Although these ?ndings need to be con?rmed within the context of the human pancreas—what cells do in vitro may not re?ect what happens in the body—they provide new insights into the early stages of type 1 diabetes that could suggest ways to prevent or stop its development. the pancreatic islets of Langerhans (groups of specialized cells that regulate blood sugar levels) are destroyed by DOI: 10.1371/journal.pmed.0030051.g001 IL-1 causes nuclear membrane breakdown lymphocytes. Type 1 diabetes affects about one in 500 American children and adolescents; the only treatment is daily insulin injections. β-cell death is