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The prevalence of obesity is increasing at an alarming rate, and the obesity epidemic is driving the epidemic in type 2 diabetes. High-risk obesity is characterized by abdominal obesity with evidence of abnormal glucose and lipid metabolism, and a state of heightened inflammation.With increasing body weight, lipid accumulation occurs not only in adipose tissue, but in other organs as well. This ‘lipotoxicity’ in liver, muscle, islets, and elsewhere may account for many of the features of the metabolic syndrome. Adipose tissue produces many proteins, some of which are inflammatory cytokines, and others of which are antiinflammatory or which improve insulin sensitivity.The treatment of obesity requires the identification of the high-risk patient, and the institution of lifestyle measures with a long-term outlook, and an avoidance of heavily marketed fads. Current research will likely lead to improved medications in the future.