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Diabetes

Diabetes and Periodontal Infection: It’s a Two Way Street

How Are Diabetes and Gum Disease Connected?

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FACT: Periodontal disease treatment can result in a 0.4% reduction in HbA1c levels

Terminology

What Can Be Done?

Helpful Scientific Studies

Case Study #1: Periodontal disease and diabetes – A two way street.

A large evidence base suggests that diabetes is associated with an increased prevalence, extent and severity of gingivitis and periodontitis. Furthermore, numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. While inflammation plays an obvious role in periodontal diseases, evidence in the medical literature also supports the role of inflammation as a major component in the pathogenesis of diabetes and diabetic complications. Research suggests that, as an infectious process with a prominent inflammatory component, periodontal disease can adversely affect the metabolic control of diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have a positive effect on the diabetic condition, although evidence for this remains somewhat equivocal.

Mealey BL, JADA, Vol.137, Oct.2006 Supplement, pp.26s-31s.

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.

Grossi SG, Genco RJ. Ann Periodontol. 1998 Jul;3(1):51-61 61.

Case Study #2: Diabetic patients have risk for periodontal disease

Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

Hotamisligil GS, Shargill NS, et al., Science. 1993 Jan 1;259(5091):87-91.,

Abstract Attitudes, awareness and oral health-related quality of life in patients with diabetes. The purpose of this study was to assess the knowledge diabetic patients have of their risk for periodontal disease, their attitude towards oral health and their oral health-related quality of life (OHRQL).

One hundred and one consecutive patients (age range 31-79 years) recruited from a diabetic outpatient clinic participated in the study. Twenty-seven per cent of participants had type 1 diabetes, 66% type 2 and 7% did not know what type of diabetes they had. The length of time since participants were diagnosed as diabetic ranged from 1 to 48 years. Metabolic control of diabetes as determined by HbA1c levels ranged from 6.2% to 12.0% compared with the normal range of 4.5-6.0%.

Thirty-three per cent of participants were aware of their increased risk for periodontal disease, 84% of their increased risk for heart disease, 98% for eye disease, 99% for circulatory problems and 94% for kidney disease. Half of the participants who were aware of their increased risk for periodontal disease had received this information from a dentist. Dental attendance was sporadic, with 43% reporting attendance within the last year. OHRQL was not significantly affected by the presence of diabetes in the group surveyed, in comparison with a previous survey of nondiabetic patients.

A significant association was found between metabolic control and dentate status. Awareness of the potential associations between diabetes, oral health and general health needs to be increased in diabetic patients.

Allen EM, Ziada HM, et al. J Oral Rehab, 2008 March;35(3):218-23.

Case Study #3: Periodontal problems can complicate the management of diabetes and uncontrolled diabetes may aggravate periodontal disease

Recent studies indicate that the majority of the U.S. population has some periodontal disease including the most common form, chronic adult periodontitis, formerly known as pyorrhea.

Bidirectional Interrelationships Between Diabetes and Periodontal Diseases: An Epidemiologic Perspective. The evidence reviewed supports viewing the relationship between diabetes and periodontal diseases as bidirectional.

Taylor G. Annals of Periodontology, 2001, Vol. 6, No. 1, Pages 99-112.

Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome. Background-Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers.

We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects. Methods and Results – We studied the relation of Creactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (SI SI) was measured by a ) frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay.

All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), SI SI, and , fasting insulin and proinsulin (all correlation coefficients >0.3, P P

Conclusions-We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to SI SI. These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing . treatment strategies in healthy individuals with features of IRS.

Festa A, D’Agostino R, et al. Circulation 2000;102:42.

Case Study #4: Effect of Periodontitis on Insulin Resistance and the Onset of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats

Background: Studies indicate that an association exists between periodontitis and type 2 diabetes mellitus (T2DM) and/or obesity, with chronic inflammation hypothesized as the common denominator. The purpose of this study was to determine the causal effect of periodontitis and the concomitant impact of diet on the onset of insulin resistance (IR) and T2DM using a rat model system that simulates human obesity and T2DM.

Methods: Twenty- Twentyeight, 5-week-old female eight, Zucker diabetic fatty (ZDF, fa/fa fa) rats were divided into four groups of seven animals: high-fat ) fed-periodontitis (HF/P), high-fat fed-no periodontitis (HF/C), low-fat fed-periodontitis (LF/P), and low-fat fed-no periodontitis (LF/C). Periodontitis was induced by ligature placement. Fasting plasma insulin and glucose levels were measured, and glucose tolerance tests were performed to assess glucose homeostasis, IR, and the onset of T2DM. The level of tumor necrosis factor-alpha (TNF-a), leptin, triglycerides, and free fatty acids were determined in week 13 at sacrifice.

Results: HF/P rats developed more severe IR compared to HF/C rats (P125 mg/dl) 2 weeks earlier than HF/C rats. There was no difference in the severity and onset of IR and T2DM between LF/P and LF/C rats. The level of TNF-a was significantly higher in HF/P rats compared to HF/C rats (P

Conclusion: Periodontitis accelerated the onset of severe IR and impaired glucose homeostasis in high-fat fed ZDF rats. rats.

Watanabe K, Petro B, et al. Journal of Periodontology, 2008, Vol. 79, No. 7, Pages 1208-1216.

Heightened Gingival Inflammation and Attachment Loss in Type 2 Diabetics With Hyperlipidemia Hyperlipidemia. This confirms our earlier work in the diabetic rat model. These studies indicate that decreased metabolic control in type 2 diabetics results in increased serum triglycerides and has a negative influence on all clinical measures of periodontal health, particularly in patients without preexisting periodontitis.

Levels of the cytokine IL-1ß showed a trend for increasing as diabetic control diminished. In contrast, levels of the growth factor PDGF, which normally increase in periodontitis, decreased in poorly controlled diabetics with periodontitis.

These studies suggest a possible dysregulation of the normal cytokine/growth factor signaling axis in poorly controlled type 2 diabetics that may contribute to periodontal breakdown/diminished repair.

Cutler CW, Machen RL, et al. J Periodontol 1999;70:1313-1321 1321.

Inflammation. Research has uncovered a link between inflammation and diabetes as well. In the Cardiovascular Health Study, the quartile of people with the highest CRP levels were three to four times more likely to develop diabetes within three to four years of the study than the quartile of people with the lowest levels of CRP.

Some researchers speculate that Type 2 diabetes and atherosclerosis may be caused by some of the same underlying mechanisms-and that one of these mechanisms may be inflammation. portunities for using antiinflammatory strategies to correct the metabolic consequences of excess adiposity.. TNF-a, IL IL-6, resistin, and undoubtedly -other pro- or antiinflammatory cytokines appear to participate in the induction and maintenance of the subacute inflammatory state associated with obesity.

MCP-1 and other chemokines have essential roles in the recruitment of macrophages to adipose tissue. These cytokines and chemokines activate intracellular pathways that promote the development of insulin resistance and T2D.

Shoelson SE, Lee J, Goldfine AB. J. Clin. Invest. 116(7):1793-1801(2006).

Case Study #5: Clinical and Metabolic Changes After Conventional Treatment of Type 2 Diabetic Patients With Chronic Periodontitis Periodontitis

The aim of this study was to compare the response to conventional periodontal treatment between patients with or without type 2 diabetes mellitus from a clinical and metabolic standpoint. Both groups of patients showed a clinical improvement after basic non-surgical periodontal treatment. The diabetic patients showed improved metabolic control (lower HbA1c) at 3 and 6 months after periodontal treatment.

Faria-Almeida R, Navarro A, et. al, Journal of Periodontology 2006.050084.

C-Reactive Protein and Incident Cardiovascular Events Among Men With Diabetes. Several large prospective studies have shown that baseline levels of C-reactive protein (CRP) are an independent predictor of cardiovascular events among apparently healthy individuals. However, prospective data on whether CRP predicts cardiovascular events in diabetic patients are limited so far. High plasma levels of CRP were associated with an increased risk of incident cardiovascular events among diabetic men, independent of currently established lifestyle risk factors, blood lipids, and glycemic control.

Schulze M, Rimm EB, et.al. Diabetes Care 27:889-894, 2004.

Dental considerations for the treatment of patients with diabetes mellitus. The susceptibility to periodontal disease-often called the “sixth complication of diabetes mellitus”-is the most common oral complication of diabetes. The patient with poorly controlled diabetes is at greater risk of developing periodontal disease. The dental team can improve the metabolic control of a patient’s diabetes by maintaining optimal oral health.

Vernillo AT, J Am Dent Assoc, Vol 134, No suppl_1, 24S-33S.

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