Diabetic periodontitis: possible lipid‐induced defect in tissue repair through alteration of macrophage phenotype and function

BACKGROUND: Diabetes mellitus is a major health problem in the United States affecting approximately 13 million people. The five ‘classic’ complications which have historically been associated with the condition are microangiopathy, neuropathy, nephropathy, microvascu‐lar disease, and delayed wound healing. Recently, per‐iodontal disease (PD) has been declared the ‘sixth’ major complication of diabetes as diabetics demonstrate an increased incidence and severity of PD. The cellular and molecular basis for diabetic PD is unknown. HYPOTHESIS: Recent evidence suggests that PD and delayed dermal wound healing may be manifestations of the same general systemic deficit in diabetes involving impairment of the cellular and molecular signal of wounding via alterations in macrophage phenotype. Diabetes‐induced hyperlipidemia may interfere with the normal cellular and molecular signal of wounding by alteration of macrophage function and subsequent dysregulation of cytokines at the wound site. RESULTS: Preliminary data in both animal models and humans suggests that hyperglycemia, in combination with elevations of serum low density lipoproteins and tri‐glycerides, leads to formation of advanced glycation end products (AGES) which may alter macrophage phenotype. This may be responsible for dysregulation of macrophage cytokine production and increased inflammatory tissue destruction and alveolar bone loss. IMPLICATIONS: Future investigations will consider diabetic PD in the context of a generalized systemic wound healing deficit that manifests as PD in the face of constant pathologic wounding of the gingiva (bacterial plaque) or delayed dermal wound healing in instances of periodic traumatic wounding to other parts of the body. These types of studies will provide information concerning defective tissue repair in diabetics that will have clinical relevance for the understanding of PD and delayed dermal healing as well as applications of appropriate and specific therapies.