**1. Introduction**

Diabetes mellitus is characterized by chronic hyperglycemia and an altered cellular homeostasis, which lead to diffuse vascular damage and multi-organ dysfunction. Diabetic patients

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

risk both micro- and macro-vascular complications: the former result from damage to retinal, renal, and neural tissues, which is the cause of blindness, end-stage renal failure, and non-traumatic lower limb amputation, respectively [1]. Here, we will focus on diabetic wound. Impaired wound healing is associated with increased morbidity and mortality in diabetes mellitus. The majority of non-healing wounds often lead to amputation, increasing the direct costs of their care, rehabilitation, and lost productivity [2].

According to a national survey, the prevalence of chronic cutaneous wounds among hospitalized patients was 1.7% in China. The leading causes were diabetes (31.3% men, 35.3% women) and trauma (26.4% men, 19.2% women). Therefore, diabetes has recently become the leading cause of chronic cutaneous wounds in China [3]. In Shuliang Lu's study, it was indicated that new diabetic foot ulcers were already in poor condition when patients first visited the diabetic foot clinic. Concomitantly, patients had worse health-related quality of life compared with the general population [4].

Several mechanisms have played a role in this condition, such as neuropathy, peripheral arterial disease, biomechanical factors, infection, and wound healing. Brownlee identifies the production of reactive oxygen species (ROS) as the unifying mechanism behind the main pathological pathways triggered by hyperglycemia, one of which leads to the formation of heterogeneous moieties called advanced glycation end products (AGEs) via non-enzymatic glycation and glycoxidation processes [5]. AGEs affect the wound healing process either directly by their interference with various components involved or indirectly through their association with diabetic neuropathy or angiopathy [6, 7]. In addition, RAGE was discovered as a receptor for AGEs, such as carboxymethyl lysine (CML) [8]. RAGE has been postulated to contribute to the development of diabetic complications [9]. The mechanism of RAGE has also been widely discussed.

In this chapter, we will present data regarding the formation and the metabolism of AGEs, the role of RAGE involved in diabetic conditions, evidence emerging from in vitro and in vivo studies as well as studies using anti-AGEs and other related agents to support a pathogenic role for AGEs in the impaired process of diabetic wound healing.
