Periodontitis and diabetes interrelationships: role of inflammation.
Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifically immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/or increased inflammatory mediators. These cytokines can produce an insulin resistance syndrome similar to that observed in diabetes and initiate destruction of pancreatic beta cells leading to development of diabetes. Thus, there is potential for periodontitis to exacerbate diabetes-induced hyperlipidemia, immune cell alterations, and diminished tissue repair capacity. It may also be possible for chronic periodontitis to induce diabetes.
Iacopino
A M
AM
Division of Prosthodontics, Marquette University School of Dentistry, Milwaukee, Wisconsin, USA. Anthony.Iacopino@marquette.edu
D016470:Bacteremia / Q000276:immunology / Q000503:physiopathology; D001424:Bacterial Infections / Q000276:immunology / Q000503:physiopathology; D018441:Biofilms; D001786:Blood Glucose / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000276:immunology / Q000503:physiopathology*; D004198:Disease Susceptibility; D015536:Down-Regulation; D019446:Endotoxemia / Q000276:immunology / Q000503:physiopathology; D006133:Growth Substances / Q000276:immunology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006949:Hyperlipidemias / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000276:immunology; D007333:Insulin Resistance / Q000502:physiology; D016209:Interleukin-8 / Q000276:immunology; D007515:Islets of Langerhans / Q000503:physiopathology; D010518:Periodontitis / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D010641:Phenotype; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation; D014945:Wound Healing
D001786:Blood Glucose; D008078:Cholesterol, LDL; D006133:Growth Substances; D018836:Inflammation Mediators; D016209:Interleukin-8; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha