Role of macrophages in complications of type 2 diabetes

Macrophage accumulation is a feature of Type 2 diabetes and is associated with the development of diabetic complications (nephropathy, atherosclerosis, neuropathy and retinopathy). The present article reviews the current evidence that macrophages contribute to the complications of Type 2 diabetes. Macrophage-depletion studies in rodent models have demonstrated a causal role for macrophages in the development of diabetic complications. Components of the diabetic milieu (high glucose, advanced glycation end-products and oxidized low-density lipoprotein) promote macrophage accumulation (via induction of chemokines and adhesion molecules) and macrophage activation within diabetic tissues. Macrophages mediate diabetic injury through a variety of mechanisms, including production of reactive oxygen species, cytokines and proteases, which result in tissue damage leading to sclerosis. A number of existing and experimental therapies can indirectly reduce macrophage-mediated injury in diabetic complications. The present article discusses the use of these therapies, given alone and in combination, in suppressing macrophage accumulation and activity. In conclusion, current evidence supports a critical role for macrophages in the evolution of diabetic complications. Present therapies are limited in slowing the progression of macrophage-mediated injury. Novel strategies that are more specific at targeting macrophages may provide better protection against the development of Type 2 diabetic complications.