Sara G. Grossi

A Proposed Model Linking Inflammation to Obesity, Diabetes, and Periodontal Infections

BACKGROUND Obesity is an important risk factor for diabetes, cardiovascular disease, and periodontal disease. Adipocytes appear to secrete proinflammatory cytokines which may be the molecules linking the pathogenesis of these diseases. We evaluated the relationship between obesity, periodontal disease, and diabetes mellitus insulin resistance as well as the plasma levels of tumor necrosis factor alpha (TNFα) and its soluble receptors (sTNFα) to assess the relationship of inflammation to obesity, diabetes, and periodontal infections. METHODS The relationship between periodontal disease, obesity, and insulin resistance was examined in the Third National Health and Nutrition Examination Survey (NHANES III). In a population of 12,367 non-diabetic subjects, the variable body mass index (BMI) was used as an assessment of obesity and periodontal disease was assessed by mean clinical attachment loss. The plasma levels of TNFα and sTNFα were assessed in subsets of 1,221 adults from Erie County, New York, who represented the highest and lowest quartile of BMI. These subjects had extensive periodontal and medical evaluations. RESULTS In the NHANES III portion of the study, BMI was positively related to severity of periodontal attachment loss (P <0.001). Weighted multiple logistic regressions showed that this relationship is likely mediated by insulin resistance, since overweight individuals (with BMI ≥27 kg/m2 ) with high levels of insulin resistance (IR) exhibited an odds ratio of 1.48 (95% confidence interval 1.13 - 1.93) for severe periodontal disease as compared to overweight subjects with low IR. In the Erie County adult population, the highest levels of TNFα and sTNFα receptors were found in those individuals in the highest quartile of BMI. A positive correlation of TNFα levels with periodontal disease was found only in those in the lowest quartile of BMI. CONCLUSIONS Obesity is a significant predictor of periodontal disease and insulin resistance appears to mediate this relationship. Furthermore, obesity is associated with high plasma levels of TNFα and its soluble receptors, which in turn may lead to a hyperinflammatory state increasing the risk for periodontal disease and also accounting in part for insulin resistance. Further studies of the molecular basis of insulin resistance and its relationship to diabetes, periodontal disease, and obesity are necessary to fully test the hypothesis that adipocyte production of proinflammatory cytokines is a pathogenic factor linking obesity to diabetes and periodontal infections.

Response to Periodontal Therapy in Diabetics and Smokers

Diabetics and smokers are two patient groups at high risk for periodontal disease who also exhibit impaired wound healing and, therefore, constitute two different groups in whom the relationship between host-parasite interaction, outcome of periodontal therapy, and systemic factors is best represented. The results of two independent clinical trials involving treatment of periodontal disease in diabetics and smokers are presented. A new treatment regimen-for the management of periodontal disease associated with diabetes mellitus is proposed. This treatment approach incorporates both antimicrobial agents and pharmacological modulation of the host response. Elimination of periodontal infection and reduction of periodontal inflammation in diabetic patients resulted in a significant short-term reduction in the concentration of glycosylated hemoglobin (HbA1c ). Control of chronic infections and modulation of the host response offer a new therapeutic approach in the management of patients with both diabetes and periodontal disease. The effect of smoking on periodontal healing is also discussed. The clinical and microbiological response of smokers to non-surgical periodontal therapy is compared to non-smokers. In addition, possible mechanisms whereby diabetes mellitus and cigarette smoking increase the severity of periodontal disease are discussed. J Periodontol 1996;67:1094-1102.

Systemic Inflammation in Cardiovascular and Periodontal Disease: Comparative Study

ABSTRACT Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, α1-acid-glycoprotein (AAG), α1-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.

Serum Cotinine Levels, Smoking, and Periodontal Attachment Loss:

Cigarette smoking and tobacco use have been the subjects of numerous studies for many years. Smoking has also been associated with periodontal disease. However, no relationship between a reliable biochemical marker and increased severity of the periodontal condition has yet been described. It was thus the aim of this study to apply the measurement of cotinine, the major metabolite of nicotine, as a quantitative method to assess levels of smoking, and to correlate serum levels of cotinine with severity of periodontal disease. The degree of association between smoking and periodontal attachment loss was investigated in a study including 79 patients 25 to 64 years old suffering from periodontitis. Patients were examined and the following parameters recorded: Gingival Assessment (GA), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), and Bone Crest Height (BCH). In addition, self-reported histories of tobacco use as well as blood samples for quantitative analysis of serum levels of cotinine were taken. The serum samples were analyzed for cotinine content by means of a competitive-inhibition ELISA technique. The differences in mean cotinine levels were statistically significant (p = 0.0001) between smokers and non-smokers, showing no overlap between the groups. Severity of periodontal attachment loss was positively correlated with serum levels of cotinine for both measures of periodontal disease (CAL p = 0.005; BCH p = 0.008). Results from the present study indicate that serum cotinine levels used as a biochemical marker of smoking status are correlated with severity of periodontal attachment loss.

Reproducibility of Probing Depth Measurements Using a Constant-Force Electronic Probe: Analysis of Inter- and Intraexaminer Variability

BACKGROUND Probing depth (PD) is a commonly used method to determine periodontal disease severity in both treating and evaluating disease progression. Agreement among examiners collecting data in scientific investigations is necessary to establish reliable criteria for determining levels of periodontal attachment loss. The objective of our study was to evaluate inter- and intraexaminer variability of PD measurements among study examiners using a constant force periodontal probe, and to compare the variability of tooth-mean and quadrant-mean. METHODS Three examiners, who had been previously trained and calibrated, performed measurements on 20 volunteers. Intraand interexaminer variability of sites was determined by means of standard error of measurement (SE). Data analysis included determination of error for both quadrant mean and tooth mean. RESULTS PD measurements for the quadrant-mean were used to calculate the intraexaminer variability, resulting in a mean (SD) value for an SE of 0.40 mm (± 0.02). Interexaminer variability for quadrant mean was 0.16 mm (± 0.02). For tooth-mean SE, the intraexaminer variability values were equal to 0.38 mm (± 0.07), and interexaminer variability equal to 0.24 mm (± 0.05). CONCLUSIONS All three examiners participating in our study were able to obtain reliable measurements for PD, using the constant force electronic probe. Reproducibility did not vary appreciably when using the whole quadrant mean compared to the tooth mean. These trained examiners were able to provide reproducible measures under 0.5 mm. J Periodontol 2003;74:1736-1740.

The Association Between Osteoporosis and Alveolar Crestal Height in Postmenopausal Women

BACKGROUND Evidence supporting an association between osteoporosis and loss of alveolar crestal bone is limited. This study investigated that association in a large cohort of postmenopausal women. METHODS A cohort of 1,341 postmenopausal women aged 53 to 85 were assessed for alveolar crestal height (ACH) and bone density. ACH was determined from oral radiographs with subjects dichotomized by disease severity. Bone density was assessed by dual energy x-ray absorptiometry, with severity determined by worst T score measured (normal >-1.00; low -1.00 to -2.00; moderate -2.01 to -2.49; osteoporotic <-2.5). RESULTS Compared to subjects in the normal T-score group, the odds of worse ACH increased by 39%, 59%, and 230% for those in the low, moderate, and osteoporotic groups, respectively. Adjustment for weight, education, hormone use, calcium or vitamin D supplementation, and smoking did not appreciably change the findings. Further adjustment for age attenuated the association, with osteoporotic subjects having a 1.9-fold increase of being in the worst ACH group (95% confidence interval [CI] 1.19 to 3.05). After age stratification, in women younger than 70 there was a significant trend by decreasing T-score category (P <0.02). Osteoporotic subjects had worse ACH (odds ratio [OR] = 1.95; 95% CI 1.20 to 3.17). In women aged 70 and older, worse ACH was 2.5- to 4.6-fold increased for decreasing T-score category. After adjustment, the OR (95% CI) for the low, moderate, and osteoporotic groups were 2.66 (1.12 to 6.29), 2.31 (0.89 to 6.01), and 3.57 (1.42 to 8.97), respectively (P trend = 0.026). CONCLUSIONS This study found a strong and consistent association between T score and ACH in postmenopausal women. Increasing age is an important modifier of that association.

Periodontal Disease and Recurrent Cardiovascular Events in Survivors of Myocardial Infarction (MI): The Western New York Acute MI Study

BACKGROUND Periodontal disease and cardiovascular disease (CVD) have been the focus of much research, but little is known about their roles in the recurrent event risk in patients with CVD. This study investigates whether periodontal disease is related to recurrent CVD events and mortality in survivors of incident myocardial infarction (MI). METHODS Participants (668 males and 216 females; mean age: 54 + or - 8.5 years) were recruited (1997 through 2004) from two western New York county hospitals and completed an interviewer-administered questionnaire regarding lifestyle habits, clinical measurements, and a comprehensive dental examination. The periodontal disease status was measured by the mean clinical attachment loss (AL). Follow-up surveys assessed hospitalizations or medical procedures; cardiovascular events were validated by medical records. A National Death Index (NDI) Plus search was conducted. The outcome was recurrent fatal and non-fatal cardiovascular events (International Classification of Diseases codes 390 to 450). RESULTS After an average follow-up of 2.9 years, 154 events were reported. Among never-smokers, the adjusted hazard ratio (95% confidence interval) for the mean clinical AL (millimeters) was 1.43 (1.09 to 1.89). No associations were found in ever-smokers (clinical AL by smoking interaction: P <0.05). CONCLUSION These findings indicate that periodontal disease may be an important factor in determining recurrent cardiovascular events in MI patients and not merely a marker for the effects of cigarette smoking.