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Purpose of review: To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1[beta].

Recent findings: Recent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1[beta] as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1[beta]-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1[beta] itself. Caspase-1 is required for IL-1[beta] activity and the release of free fatty acids from the adipocyte. An emerging hypothesis gains support from patients with type 2 diabetes in which an imbalance in the amount of IL-1[beta] agonist activity versus the specific countering by the naturally occurring IL-1 receptor antagonist (IL-1Ra) determines the outcome of islet inflammation. An important confirmation comes from clinical trials. Blockade of IL-1 receptor with anakinra, the recombinant form of IL-1Ra, or neutralizing anti-IL-1[beta] antibodies, provides proof-of-principle data that reducing IL-1[beta] activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1[beta]-mediated inflammation in the microenvironment of the islet allows for regeneration.

Summary: Monotherapy or add-on therapy targeting IL-1[beta] in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events.

(C) 2010 Lippincott Williams & Wilkins, Inc.