The role of advanced glycation end-products in the etiology of insulin resistance and diabetes

Despite new and effective drug therapies, insulin resistance (IR) and type 2 diabetes and its complications remain major medical challenges. It is known that IR, often associated with overnutrition and obesity, results from elevated oxidant stress (OS) and chronic inflammation. Less widely known is that a major cause for this inflammation is excessive consumption of advanced glycation end-products (AGEs) by the citizens of developed countries. AGEs, which were largely thought as oxidative derivatives resulting from diabetic hyperglycemia, are increasingly seen as a potential risk factor for islet β-cell injury, peripheral IR, and diabetes. This article will discuss the relationships between exogenous AGEs, chronic inflammation, IR, and type 2 diabetes. We present new insights on the failure of innate immune defense mechanisms under chronic oxidant overload, which increase susceptibility to IR and type 2 diabetes and its complications. Finally, we describe evidence on AGE restriction, a new non-pharmacologic intervention, which effectively reduces persistent IR, restores innate immune functions, and, thus, optimizes current antidiabetic drug therapies.