Inflammation and Oxidative Stress in Obesity, Metabolic Syndrome, and Diabetes

I do not think anybody even remotely connected with the field of diabetes, either as a researcher or as a health care provider, would have any serious objection to the concept that some degree of altered inflammatory activity or oxida-tive stress plays a serious role in multiple aspects of diabetes. Just to mention two of the best-known processes, a violent, acute inflammatory event leads to the destruction of beta cells at the onset of type 1 diabetes, and a chronic, subclinical proinflammatory state is at the base of the slow development of micro-and macrovascular complications accounting for the larger part of morbidity and mortality related to all forms of diabetes. This connection has led to a remarkable increase in research activity in this field in recent years. Running a PubMed search with " inflammation and diabetes " as search terms, for instance, returns 14,059 articles; " Oxidative stress and diabetes " 8850 articles; " inflammation and atheroscle-rosis " 11209 articles; and " inflammation and cardiovascular disease " 49245 articles. To a smaller extent, the very content of this special issue is a clear example of the variety and complexity of issues in the prevention, diagnosis, management, and therapy of diabetes, in which one or more inflammatory or oxidative stress component plays a critical role. Inflammation and oxidative stress, however, are two extremely broad and comprehensive terms. This wealth of studies and results certainly clarified a large number of pathways , mediators and regulatory mechanisms, genes and post-transcriptional regulators of gene expression related to inflammation and oxidative stress. However, given the very large, and constantly growing, number of cell types and molecules involved, it often feels as though the rate at which new questions accumulate far exceeds the rate at which prior questions are definitively answered. We have now identified hundreds of cytokines and chemokines, whose full physiological function remains in many cases nebulous. Terms such as " pro " or " anti-inflammatory, " earlier closely associated with individual inflammatory mediators (such as the classically defined proinflammatory interleukin-6), are now used more reluctantly, as the same molecules often display less clear-cut activity, or even shift from one end of the spectrum to the other, depending on the surrounding metabolic or cell-signaling milieu. More importantly, often only some components of the complex inflammatory network are altered in a specific pathological condition. Identifying what these components are, and using them as biomarkers of …