The diabetic ulceration is not uncommon, and becomes refractory, as the skin in a diabetic patient is relatively thin as well as hypoesthetic and less sensitive to temperature. As there are already preexisting histological and cellular derangement in the skin, healing of the skin injury is difficult, thus resulting in an intractable ulceration. When diabetes is not controlled, the skin contents of sugar and advanced glycation end product accumulate, invoking cellular deformation and accumulation of matrix metalloproteinases (MMP), resulting in an imbalance between MMP and its inhibitors, malfunction of growth factors, and inflammatory reaction. These processes lead to obvious skin thinning, denaturation of connective tissues, thickening of vascular basal membrane, and neuropathy, etc. These pathological alterations could be recognized as "covert disorder" of skin in diabetic patients and may be underlying disorders in producing indolent diabetic ulcers.
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