Th 0606wdj Chronic01

Chronic Systemic Diseases

June 1, 2006
Relating periodontal inflammation to diabetes, cardiovascular disease, and low birth weight

Relating periodontal inflammation to diabetes, cardiovascular disease, and low birth weight

by Grishondra Branch-Mays, DDS, MS

Most dental practioners have seen an increase in the number of patients who present with chronic systemic diseases. The literature is replete with reports that suggest a link between systemic and oral diseases, in particular periodontal disease. How can the dental profession practically apply this knowledge to identify and treat potential at-risk patients? Let us explore some information on periodontal inflammation in relationship to diabetes, cardiovascular disease, and pre-term births.

Click here to enlarge image

Periodontal disease is part of an inflammatory disease process initiated by a bacterial challenge. Like other inflammatory processes, periodontal breakdown involves a complex cellular and vascular response, which is ultimately aimed at elimination of the source of injury. The clinical presentation involves a varying degree of gingival inflammation, pocket formation, clinical-attachment loss, and bone loss.1 The extent and severity of the clinical presentation is affected by the composition of the bacterial flora and a complex, host-inflammatory response.

The host cells produce pro-inflammatory mediators in response to the bacterial insult. Page and Schroeder demonstrated that the principle cells present during the inflammatory process include neutrophils (PMNs), lymphocytes, plasma cells, and macrophages. As the lesion progresses, the type of cell that predominates the lesion changes.2,3 Pro-inflammatory mediators called cytokines are soluble proteins that play an important role in the pathogenesis of many inflammatory diseases.4 For example, it has been suggested that elevated levels of pro-inflammatory mediators can elicit breakdown of the periodontal tissues and intensify the severity of the disease.5 Breakdown of collagen and bone has been demonstrated to result from the presence of inflammatory mediators.6 Although our cells produce several inflammatory mediators, those that are commonly associated with loss of the periodontium include interlukin-1, interlukin-6, tumor necrosis factor, prostaglandin E-2, and several other cytokines.6,7

The influence of pro-inflammatory mediators is demonstrable in diabetic patients who also have periodontitis. Several studies concluded that the extent and severity of periodontal disease is increased in uncontrolled diabetics and showed elevated levels of pro-inflammatory mediators produced in the gingival crevicular fluid of these patients.8,9,10 The connection between diabetes and periodontal disease may also be linked to alterations in the PMN’s response that can manifest in both diabetes and some aggressive forms of periodontal disease. According to a recent meta-analysis, diabetic patients have a two-fold higher risk of developing periodontal disease.11 It is thought that diabetic patients are more susceptible to infection, hence increasing the potential for diabetic patients to be affected by periodontal infections. Other potential links can be derived from the production of advanced glycolated end products associated with poor glycemic control. A prolonged increase in glycolated products in the blood stream is associated with collagen breakdown.12 Because of the alterations in the cellular and vascular response and the effect on bone and collagen metabolism, it is reasonable to contemplate an increase in the severity and extent of clinical findings for patients affected by both diseases.

A plausible association with periodontal disease and cardiovascular disease or pre-term birth is the potential for oral bacteria to educe a systemic response. There is some evidence that oral pathogens and pro-inflammatory mediators present in periodontal disease can stimulate the production of acute phase proteins such as C-reactive protein.13 C-reactive protein acts as a measure of the concentration of a protein in serum suggestive of the presence of acute inflammation. One study showed that oral bacteria resulted in a systemic response which was associated with cardiovascular events.14 In males with severe periodontal disease, elevated levels of C-reactive protein were found in comparison to periodontally healthy patients.15 Another study suggested that by extraction of periodontally involved teeth, the level of systemic markers of cardiovascular disease were reduced16, suggesting treatment of periodontitis could lower the risk for cardiovascular disease. Similarly, oral bacteria may have implications in pre-term, low-weight infant births.17,18,19 It was recently reported that the presence of oral bacteria in the uterus of pregnant rats increased the risk of stillbirths and pre-term births.19 Hence, the presence of oral bacteria invading endothelial cells20, the placenta, and amniotic fluids and the ability of the bacteria to stimulate an immune response build a realistic circumstance linking periodontal disease with cardiovascular disease and pre-term birth.

Although the literature suggests associations between the diseases, many of the reports conclude that these relationships are circumstantial. There are studies that have not found clinical measures of periodontal disease to be a factor in cardiovascular disease, show no clear relationship between pre-term birth and periodontitis, and do not show evidence that treating a patient’s periodontal disease will result in improved glycemic control. It has been suggested that future research is necessary to elucidate the extent of the link with periodontal disease to diabetes, cardiovascular disease, and pre-term births. We face many confounders, which have not allowed for more conclusive evidence. Many chronic systemic diseases have similar risk factors such as smoking, obesity, and stress, and completely controlling for these variables is a daunting task. Comparison of the studies is also complex because of the variance in research methodology, which could include but is not limited to the high cost associated with randomized clinical trials, patient demographics, or including a control group in the study. Although the current knowledge of these associations is inconclusive and consequently does not allow us to make specific causal-and-effect relationships at this time, we should develop reasonable strategies to assist us in making appropriate treatment decisions for our patients.

For example, we should remain up to date on current medical and dental literature on the systemic-oral connection, set up health care provider networks to allow for consultation and dissemination of information for patients with multiple chronic diseases who are often at greater risk for other diseases, provide patients with updated information on the importance of dental health with emphasis on reducing risk factors commonly associated with chronic systemic disease, and provide appropriate treatment options for patients with periodontal disease.


1 Fleming, TF. Annuals of Periodontology, Vol. 4 1999.

2 Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest 1976: 33:235-249

3 Page RC, Simpson DM, Ammons WF. Host tissue response in chronic inflammatory periodontal disease. IV. The periodontal and dental status of a group of aged great apes. J Periodntol 1975: 46:144-155.

4 Okada H, Murakami S. Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med. 1998: 9:248-66.

5 Baker PJ. The role of immune responses in bone loss during periodontal disease. Microbes Infect 2000: 2:1181-1192.

6 van der Zee E, Everts V, Beertsen W. Cytokines modulate routes of collagen breakdown. Review with special emphasis on mechanisms of collagen degradation in the periodontium and the burst hypothesis of periodontal disease progression. J Clin Periodontol. 1997: 24:297-305.

7 McCauley LK, Nohutcu RM. Mediators of periodontal osseous destruction and remodeling: principles and implications for diagnosis and therapy. J Periodontol. 2002: 73:1377-91.

8 Iacopino AM. Periodontitis and diabetes interrelationships: role of inflammation. Ann Periodontol. 2001. 6:125-37.

9 Safkan-Seppala B, Sorsa T, Tervahartiala T, Beklen A, Konttinen YT. Collagenases in gingival crevicular fluid in type 1 diabetes mellitus. J Periodontol. 2006: 77:189-94.

10 Engebretson SP, Hey-Hadavi J, Ehrhardt FJ, Hsu D, Celenti RS, Grbic JT, Lamster IB. Gingival crevicular fluid levels of interleukin-1beta and glycemic control in patients with chronic periodontitis and type 2 diabetes. J Periodontol. 2004: 75:1203-8.

11 Faria-Almeida R, Navarro A, Bascones, A. Clinical and metabolic changes after conventional treatment of type 2 diabetic patients with chronic periodontitis. J Periodontol. 2006: 77: 591-598.

12 Takeda M, Ojima M, Yoshioka H, Inaba H, Kogo M, Shizukuishi S, Nomura M, Amano A. Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients. J Periodontol. 2006: 77:15-20.

13 De Nardin E. The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease. Ann Periodontol. 2001: 6:30-40

14 Beck JD, Eke P, Heiss G, Madianos P, Couper D, Lin D, Moss K, Elter J, Offenbacher S. Periodontal disease and coronary heart disease: a reappraisal of the exposure. Circulation. 2005: 112:19-24.

15 Briggs JE, McKeown PP, Crawford VL, Woodside JV, Stout RW, Evans A, Linden GJ. Angiographically confirmed coronary heart disease and periodontal disease in middle-aged males. J Periodontol. 2006: 77:95-102.

16 Taylor BA, Tofler GH, Carey HM, Morel-Kopp MC, Philcox S, Carter TR, Elliott MJ, Kull AD, Ward C, Schenck K. Full-mouth tooth extraction lowers systemic inflammatory and thrombotic markers effects of maternal Campylobacter rectus infection on murine placenta, fetal and neonatal survival, and brain development. J Dent Res. 2006: 85:74-78.

17 Offenbacher S, Riché EL, Barros SP, Bobetsis YA, Lin D, Beck JD. Effects of maternal Campylobacter rectus infection on murine placenta, fetal and neonatal survival, and brain development. J Periodontol. 76:2133-2143.

18 Han YW, Ikegami A, Bissada NF, Herbst M, Redline RW, Ashmead GG. Transmission of an uncultivated bergeyella strain from the oral cavity to amniotic fluid in a case of preterm birth. J Clin Microbiol. 2006: 44:1475-83.

19 Han YW, Redline RW, Li M, Yin L, Hill GB, McCormick TS. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect Immun. 2004: 72: 2272-2279.

20 Schenkein HA, Barbour SE, Berry CR, Kipps B, Tew JG. Invasion of human vascular endothelial cells by Actinobacillus actinomycetemcomitans via the receptor for platelet-activating factor. Infect Immun. 2000: 68:5416-9.

Click here to enlarge image

Grishondra Branch-Mays, DDS, MS
Dr. Branch-Mays received her DDS degree from the University of Michigan in 1991 and her certificate and Masters of Science in Periodontics in 1994 from the University of Iowa College of Dentistry. E-mail her at [email protected].