Oral disease and subsequent cardiovascular disease in people with type 2 diabetes: a prospective cohort study based on the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.

AIMS/HYPOTHESIS: While there are plausible biological mechanisms linking oral health with cardiovascular disease (CVD) and mortality rates, no study, to our knowledge, has examined this association in a representative population of people with type 2 diabetes. METHODS: We used the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study, a large, detailed, randomised controlled trial among a general population of individuals with type 2 diabetes. For the purposes of the present analyses, data from the trial are used within a prospective cohort study design. A total of 10,958 men and women, aged 55 to 88 years and with type 2 diabetes, participated in a baseline medical examination, during which they counted their number of natural teeth and reported the number of days that their gums had bled over the preceding year. Study members were followed up for mortality and morbidity over 5 years. RESULTS: After controlling for a range of potential confounding factors, the group with no teeth had a markedly increased risk of death due to all causes (HR 1.48, 95% CI 1.24-1.78), CVD (1.35, 1.05-1.74) and non-CVD (1.64, 1.26-2.13), relative to the group with the most teeth (≥22 teeth). Frequency of bleeding gums was not associated with any of the outcomes of interest. There was no suggestion that treatment group or sex modified these relationships. CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes, oral disease, as indexed by fewer teeth, was related to an increased risk of death from all causes and of death due to CVD and non-CVD.

SAA and PLTP activity in plasma of periodontal patients before and after full-mouth tooth extraction.

OBJECTIVE: To assess whether treatment of advanced periodontal disease affects plasma levels of serum amyloid A (SAA) and phospholipid transfer protein (PLTP) activity. DESIGN: We measured the levels of SAA and PLTP activity in plasma of 66 patients with advanced periodontal disease before and after treatment by full-mouth tooth extraction (FME). RESULTS: At baseline, median SAA levels in our study population were within the normal range (2.7 microg ml(-1)) but SAA was elevated (>5 microg ml(-1)) in 18% of periodontitis patients. Three months after FME, SAA levels were significantly reduced (P = 0.04). SAA did not correlate with any of the periodontal disease parameters. PLTP activity was elevated in patients with periodontitis, compared to the PLTP activity reference group (age-matched systemically healthy adults, n = 29; 18 micromol ml(-1) h(-1)vs 13 micromol ml(-1) h(-1), respectively, P = 0.002). PLTP activity inversely correlated with average periodontal pocket depth (PPD) per tooth (r(s) = -0.372; P = 0.002). Three months after FME, median PLTP activity did not change significantly. CONCLUSIONS: Full-mouth tooth extraction significantly reduces SAA, a marker of inflammation, while it does not affect plasma PLTP activity. However, the inverse correlation between PLTP activity and average PPD suggests that increased PLTP activity may limit periodontal tissue damage.

Full-mouth tooth extraction lowers systemic inflammatory and thrombotic markers of cardiovascular risk.

Prior studies of a link between periodontal and cardiovascular disease have been limited by being predominantly observational. We used a treatment intervention model to study the relationship between periodontitis and systemic inflammatory and thrombotic cardiovascular indicators of risk. We studied 67 adults with advanced periodontitis requiring full-mouth tooth extraction. Blood samples were obtained: (1) at initial presentation, immediately prior to treatment of presenting symptoms; (2) one to two weeks later, before all teeth were removed; and (3) 12 weeks after full-mouth tooth extraction. After full-mouth tooth extraction, there was a significant decrease in C-reactive protein, plasminogen activator inhibitor-1 and fibrinogen, and white cell and platelet counts. This study shows that elimination of advanced periodontitis by full-mouth tooth extraction reduces systemic inflammatory and thrombotic markers of cardiovascular risk. Analysis of the data supports the hypothesis that treatment of periodontal disease may lower cardiovascular risk, and provides a rationale for further randomized studies.

The genes for mouse salivary androgen-binding protein (ABP) subunits alpha and gamma are located on chromosome 7.

We demonstrate that the previously described gene Androgen binding protein (Abp; Dlouhy and Karn, 1984) codes for the Alpha subunit of ABP and rename the locus Androgen binding protein alpha (Abpa). A study of recombinant inbred strains demonstrates that Abpa is located on chromosome 7 near Glucose phosphate isomerase-1 (Gpi-1). Biochemical and genetic evidence indicates the existence of another ABP subunit, Gamma, and its locus, Androgen binding protein gamma (Abpg), that is closely linked to Abpa. Although no polymorphism has yet been found for the previously described Beta subunit of ABP (Dlouhy and Karn, 1983; 1984), we suggest that it represents a third locus. Androgen binding protein beta (Abpb). ABP subunits appear to dimerize randomly and a model is presented demonstrating the origin of six ABP dimers in the salivas of AbpaaAbpga/AbpabAbpgb heterozygous mice. The results of cell-free translation studies in which the pre-ABP subunits are identified specifically by immunoprecipitation with anti-ABP antibody supports the idea that independent mRNAs code for the Alpha, Beta and Gamma subunits.

Evaluation of anti-AIDS drugs in conventional mice implanted with a permeable membrane device containing human T cells infected with HIV.

We now report the confirmation of the work of Hollingshead et al. (1995) on development of a cell based hollow fiber (HF) system for evaluating potential anti-AIDS drugs in vivo using conventional mice rather than SCID mice. CD4 +, CEM-SS cells infected with HIV/1, strain RF, at a multiplicity of infection of 0.1 were placed into HFs. The fibers were implanted into the peritoneal cavity of outbred Swiss mice. Using this model, the antiviral activity of azidothymidine (AZT) at doses of approximately 150, 75 and 37.5 mg/kg/day was evaluated by administering AZT to the mice in drinking water. Upon fiber removal on day 6, AZT treatment was shown to significantly increase CEM cell viability over the untreated, virus control group and significantly reduced the levels of HIV p24 and HIV RT activity.

Oral disease in relation to future risk of dementia and cognitive decline: prospective cohort study based on the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.

OBJECTIVE: Examine the association of oral disease with future dementia/cognitive decline in a cohort of people with type 2 diabetes. METHODS: A total of 11,140 men and women aged 55-88 years at study induction with type 2 diabetes participated in a baseline medical examination when they reported the number of natural teeth and days of bleeding gums. Dementia and cognitive decline were ascertained periodically during a 5-year follow-up. RESULTS: Relative to the group with the greatest number of teeth (more than or equal to 22), having no teeth was associated with the highest risk of both dementia (hazard ratio; 95% confidence interval: 1.48; 1.24, 1.78) and cognitive decline (1.39; 1.21, 1.59). Number of days of bleeding gums was unrelated to these outcomes. CONCLUSIONS: Tooth loss was associated with an increased risk of both dementia and cognitive decline.

Management of drug-induced gingival enlargement with orthodontic complications.

Gingival enlargement (GE) may be induced by cyclosporin A, phenytoin or calcium channel blockers, used either singly or in combination. The lesion can cause significant disfigurement and functional difficulty as it interferes with eating and speech, impedes effective plaque control, and disturbs occlusal relationships. Orthodontic problems may originate independently of the soft tissue lesion or they may develop secondary to the GE. Management of drug-induced GE with orthodontic complications requires co-operative teamwork. This will be discussed in the management of cases with medical, orthodontic and periodontal interventions.

Microvascular angiopathy in advanced periodontal disease.

Previous studies have shown a perivascular hyaline thickening affecting restricted regions of the microcirculation in gingivitis and moderate periodontitis and in the pulpal vessels in chronic pulpitis. In the present study of the lesion of advanced periodontitis, immunostaining for type IV collagen and laminin demonstrated widespread deposition of basement membrane material, with manifest involvement of the venous network. Some vessels were associated with an increased deposition of both basement membrane proteins, while others showed preferential deposition of either laminin or type IV collagen. Immunostaining also revealed an extensive trabecular network of type IV collagen throughout the affected gingival tissue that was related to recognizable vessels but was co-extensive with less intense staining for laminin. This network was not associated with viable endothelial cells demonstrable by staining with the endothelial marker Ulex agglutinin (UEA-1). The results indicate extensive vascular pathology in advanced periodontitis that could explain the attenuation of the inflammatory reaction and the restricted ability to develop reparative granulation tissue in this disease.

Genetic and dietary interactions in the regulation of HMG-CoA reductase gene expression.

Inbred strains of mice exhibit large genetic variations in hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. A tissue-specific genetic variation between the strains BALB/c and C57BL/6, resulting in about 5-fold higher levels in hepatic reductase activity in strain C57BL/6, was examined in detail. The activity difference between these two strains could be explained entirely by differences in hepatic reductase mRNA levels. In genetic crosses, the variation segregated as a single major Mendelian element. Surprisingly, the mode of inheritance was recessive since F1 mice exhibited the BALB/c levels of enzyme activity. Despite the fact that the rates of hepatic sterol synthesis also differed between the strains by a factor of about five, the altered hepatic reductase expression did not significantly influence plasma lipoprotein levels. The response to a high cholesterol, high fat diet between the strains was remarkably different. Thus, in BALB/c mice, both hepatic reductase activity and mRNA levels were affected only slightly, if at all, by cholesterol feeding, while in strain C57BL/6 mice both were reduced more than 10-fold by cholesterol feeding. Several lines of evidence, including analysis of cis-acting regulatory elements, the nonadditive mode of inheritance, and genetic studies of the HMG-CoA reductase gene locus on mouse chromosome 13, support the possibility that the variation in reductase expression is not due to a mutation of the structural gene but, rather, is determined by a trans-acting factor controlling reductase mRNA levels. The variation provides a striking example, at the molecular level, of the importance of dietary-genetic interactions in the control of cholesterol metabolism.