Periodontal disease and diabetes mellitus: a two-way relationship.

Severe periodontal disease often coexists with severe diabetes mellitus. Diabetes is a risk factor for severe periodontal disease. A model is presented whereby severe periodontal disease increases the severity of diabetes mellitus and complicates metabolic control. We propose that an infection-mediated upregulation cycle of cytokine synthesis and secretion by chronic stimulus from lipopolysaccharide (LPS) and products of periodontopathic organisms may amplify the magnitude of the advanced glycation end product (AGE)-mediated cytokine response operative in diabetes mellitus. In this model, the combination of these 2 pathways, infection and AGE-mediated cytokine upregulation, helps explain the increase in tissue destruction seen in diabetic periodontitis, and how periodontal infection may complicate the severity of diabetes and the degree of metabolic control, resulting in a 2-way relationship between diabetes mellitus and periodontal disease/infection. This proposed dual pathway of tissue destruction suggests that control of chronic periodontal infection is essential for achieving long-term control of diabetes mellitus. Evidence is presented to support the hypothesis that elimination of periodontal infection by using systemic antibiotics improves metabolic control of diabetes, defined by reduction in glycated hemoglobin or reduction in insulin requirements.

[1]  C. Greenbaum,et al.  Short-term responses to periodontal therapy in insulin-dependent diabetic patients. , 1996, Journal of periodontology.

[2]  I. Ishikawa,et al.  Induction of the immune response to periodontopathic bacteria and its role in the pathogenesis of periodontitis. , 1997, Periodontology 2000.

[3]  G. Bedi,et al.  Purification and characterization of a collagen-degrading protease from Porphyromonas gingivalis. , 1994, The Journal of biological chemistry.

[4]  H. M. Lee,et al.  Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  W. Knowler,et al.  Type 2 diabetes mellitus and periodontal disease. , 1990, Journal of the American Dental Association.

[6]  J. Sconyers,et al.  Relationship of bacteremia to toothbrushing in patients with periodontitis. , 1973, Journal of the American Dental Association.

[7]  G. Keusch,et al.  Infection and diabetes: the case for glucose control. , 1982, The American journal of medicine.

[8]  W. Knowler,et al.  Periodontal Disease and NIDDM in Pima Indians , 1990, Diabetes Care.

[9]  M. Brownlee,et al.  Glomerular Basement Membrane Metabolism in the Diabetic Rat: In Vivo Studies , 1979, Diabetes.

[10]  P. Papapanou,et al.  Periodontal diseases: epidemiology. , 1996, Annals of periodontology.

[11]  L. Golub,et al.  Blocking Periodontal Disease Progression by Inhibiting Tissue-Destructive Enzymes: A Potential Therapeutic Role for Tetracyclines and Their Chemically-Modified Analogs. , 1993, Journal of periodontology.

[12]  R. Page,et al.  The microbial challenge in periodontitis. , 1997, Periodontology 2000.

[13]  W. Knowler,et al.  Severe Periodontitis and Risk for Poor Glycemic Control in Patients with Non-Insulin-Dependent Diabetes Mellitus. , 1996, Journal of periodontology.

[14]  M. Brownlee,et al.  Glycation Products and the Pathogenesis of Diabetic Complications , 1992, Diabetes Care.

[15]  J L Witztum,et al.  Nonenzymatic Glucosylation of Low-Density Lipoprotein Alters Its Biologic Activity , 1982, Diabetes.

[16]  G. Schmalz,et al.  Healing response to non-surgical periodontal therapy in patients with diabetes mellitus: clinical, microbiological, and immunologic results. , 1998, Journal of clinical periodontology.

[17]  G. Sundqvist Pathogenicity and virulence of black-pigmented gram-negative anaerobes. , 1993, FEMS immunology and medical microbiology.

[18]  C. Lang,et al.  Sepsis-induced insulin resistance in rats is mediated by a beta-adrenergic mechanism. , 1992, The American journal of physiology.

[19]  L. Golub,et al.  Tetracycline administration increases protein (presumably procollagen) synthesis and secretion in periodontal ligament fibroblasts of streptozotocin-induced diabetic rats. , 1992, Journal of periodontal research.

[20]  A. Hugoson,et al.  Periodontal conditions in insulin-dependent diabetics. , 1989, Journal of clinical periodontology.

[21]  S. Offenbacher Periodontal diseases: pathogenesis. , 1996, Annals of periodontology.

[22]  Clark Cm,et al.  Prevention and Treatment of the Complications of Diabetes Mellitus , 1995 .

[23]  Y. Konttinen,et al.  The anticollagenolytic potential of lymecycline in the long-term treatment of reactive arthritis. , 1992, Arthritis and rheumatism.

[24]  K. Manogue,et al.  Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. , 1988, Science.

[25]  G. King,et al.  Activation of protein kinase C by elevation of glucose concentration: proposal for a mechanism in the development of diabetic vascular complications. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[26]  G. Webster,et al.  Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin. Involvement of protein kinase C. , 1994, Archives of dermatology.

[27]  Y. Konttinen,et al.  Cellular source and tetracycline-inhibition of gingival crevicular fluid collagenase of patients with labile diabetes mellitus. , 1992, Journal of clinical periodontology.

[28]  H. Löe Periodontal Disease: The sixth complication of diabetes mellitus , 1993, Diabetes Care.

[29]  D. Nathan,et al.  Long-term complications of diabetes mellitus. , 1993, The New England journal of medicine.

[30]  R. Genco,et al.  Periodontal disease in non-insulin-dependent diabetes mellitus. , 1991, Journal of periodontology.

[31]  W. Mcarthur,et al.  Leukotoxic activity in different strains of the bacterium Actinobacillus actinomycetemcomitans isolated from juvenile periodontitis in man. , 1981, Archives of oral biology.

[32]  P. Bennett,et al.  Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota. , 1978, American journal of epidemiology.

[33]  M. Brownlee Glycation and Diabetic Complications , 1994, Diabetes.

[34]  A. Cerami,et al.  High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macromolecules. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Y. Konttinen,et al.  Doxycycline in the protection of serum alpha-1-antitrypsin from human neutrophil collagenase and gelatinase , 1993, Antimicrobial Agents and Chemotherapy.

[36]  R. Tapping,et al.  Lipopolysaccharide dependent cellular activation. , 1997, Journal of periodontal research.

[37]  Y. Konttinen,et al.  Specificity of the anticollagenase action of tetracyclines: relevance to their anti-inflammatory potential , 1992, Antimicrobial Agents and Chemotherapy.

[38]  A. Hugoson,et al.  Periodontal disease experience in adult long-duration insulin-dependent diabetics. , 1993, Journal of clinical periodontology.

[39]  M. Reding,et al.  The relationship between reduction in periodontal inflammation and diabetes control: a report of 9 cases. , 1992, Journal of periodontology.

[40]  P. Lönnroth Regulation of insulin action at the cellular level. , 1991, Journal of internal medicine. Supplement.

[41]  R. Genco Molecular pathogenesis of periodontal disease , 1994 .

[42]  B. McBride,et al.  Experimental transient bacteraemias in human subjects with varying degrees of plaque accumulation and gingival inflammation. , 1977, Journal of clinical periodontology.

[43]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[44]  N. Istfan,et al.  Effects of systemic infusions of endotoxin, tumor necrosis factor, and interleukin-1 on glucose metabolism in the rat: relationship to endogenous glucose production and peripheral tissue glucose uptake. , 1994, Metabolism: clinical and experimental.

[45]  J. Potempa,et al.  Porphyromonas gingivalis proteinases as virulence factors in the development of periodontitis. , 1997, Journal of periodontal research.

[46]  A. Cerami,et al.  Nonenzymatic glycosylation and the pathogenesis of diabetic complications. , 1984, Annals of internal medicine.

[47]  J. Ainamo,et al.  A site-by-site follow-up study on the effect of controlled versus poorly controlled insulin-dependent diabetes mellitus. , 1994, Journal of clinical periodontology.

[48]  A. Schmidt,et al.  Advanced glycation endproducts (AGEs) induce oxidant stress in the gingiva: a potential mechanism underlying accelerated periodontal disease associated with diabetes. , 1996, Journal of periodontal research.

[49]  R. Williams,et al.  Periodontal disease and diabetes in young adults. , 1960, Journal of the American Medical Association.

[50]  T. V. Van Dyke,et al.  The acute inflammatory response and the role of phagocytic cells in periodontal health and disease. , 1997, Periodontology 2000.

[51]  S. Amar,et al.  Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes. , 1994, Journal of immunology.

[52]  R. Page,et al.  The host response to the microbial challenge in periodontitis: assembling the players. , 1997, Periodontology 2000.

[53]  G. Viberti,et al.  Single-blind studies of the effects of improved periodontal health on metabolic control in type 1 diabetes mellitus. , 1995, Journal of clinical periodontology.

[54]  L. Shapira,et al.  Tetracycline inhibits Porphyromonas gingivalis lipopolysaccharide-induced lesions in vivo and TNF alpha processing in vitro. , 1997, Journal of periodontal research.

[55]  A. Cerami,et al.  The biochemistry of the complications of diabetes mellitus. , 1981, Annual review of biochemistry.

[56]  R. Genco,et al.  Treatment of periodontal disease in diabetics reduces glycated hemoglobin. , 1997, Journal of periodontology.

[57]  M. Papa,et al.  Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. , 1995, The Journal of biological chemistry.

[58]  B. Mealey Periodontal implications: medically compromised patients. , 1996, Annals of periodontology.

[59]  S. Socransky,et al.  Microbial etiological agents of destructive periodontal diseases. , 1994, Periodontology 2000.