Diabetes mellitus, caused by the malfunction of insulin-dependent glucose and lipid metabolism, presents with the classical triad of symptoms: polydypsia, polyuria, and polyphagia which are often accompanied by chronic fatigue and loss of weight. Complications of diabetes mellitus include retinopathy, nephropathy, neuropathy, and cardiovascular disease. Periodontal diseases are infections affecting the periodontium and resulting in the loss of tooth support. The association between diabetes mellitus and periodontitis has long been discussed with conflicting conclusions. Both of these diseases have a relatively high incidence in the general population (diabetes 1% to 6% and periodontitis 14%) as well as a number of common pathways in their pathogenesis (both diseases are polygenic disorders with some degree of immunoregulatory dysfunction). On the one hand, numerous reports indicate a higher incidence of periodontitis in diabetics compared to healthy controls, while other reports fail to show such a relationship. Clarification of this dilemma is occurring as the diagnostic criteria for periodontitis and diabetes mellitus improve, controlled studies with increased sample sizes are carried out, and the studies take into account major confounding variables that impact on the pathogenesis of both diseases. Current studies tend to support a higher incidence and severity of periodontitis in patients with diabetes mellitus. The overview looks at the bidirectional relationship between periodontitis and diabetes. An analysis of the National Health and Nutrition Examination Survey (NHANES) III data set confirms the previously reported significantly higher prevalence of periodontitis in diabetics than in non-diabetics (17.3% versus 9%). The analysis of the data also shows that the prevalence of diabetes in patients with periodontitis is double that seen in the non-periodontitis patients (12.5% versus 6.3%) and that this difference is also statistically significant. The pathogenesis of the 2 diseases is reviewed with an emphasis on common genetic and immune mechanisms. On the basis of the overview, 2 hypotheses for testing the relationship between periodontitis and diabetes are discussed. The first proposes a direct causal or modifying relationship in which the hyperglycemia and hyperlipidemia of diabetes result in metabolic alterations that may then exacerbate bacteria-induced inflammatory periodontitis. The second hypothesis proposes that a fortuitous combination of genes (gene sets) could result in a host who, under the influence of a variety of environmental stressors, could develop either periodontitis or diabetes or both.

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The safety and efficacy of a degradable, subgingivally placed drug delivery system containing 2.5 mg chlorhexidine (CHX) were evaluated in a randomized, blinded, multi-center study of 118 patients with moderate periodontitis. A split-mouth design was used to compare the treatment outcomes of scaling and root planing (SRP) alone with the combined use of SRP and the CHX in pockets with probing depths of 5 to 8 mm. The two maxillary quadrants were used for the two treatment arms of the study. Scaling and root planing was performed at baseline only, while the CHX was inserted both at baseline and at 3 months. Clinical and safety measurements including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) as well as gingivitis, plaque, and staining indices were recorded at baseline, and at 1, 3, and 6 months. The average PD reduction in the CHX-treated sites was significantly greater than in the sites receiving SRP alone at both 3 and 6 months with a mean difference of 0.42 mm (P < or = 0.01) at 6 months. The reduction in CAL at the treated sites was greater than at the SRP sites, although the difference was statistically significant at the 6-month visit only. An analysis of patients with initial probing depths of 7 to 8 mm (n = 56) revealed a significantly greater reduction in PD and CAL in those pockets treated with CHX compared to SRP at both 3 and 6 months. The mean differences between test and control sites at 6 months were 0.71 mm and 0.56 mm PD and CAL respectively.

Of the many palmoplantar keratoderma (PPK) conditions, only Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS) are associated with premature periodontal destruction. Although both PLS and HMS share the cardinal features of PPK and severe periodontitis, a number of additional findings are reported in HMS including arachnodactyly, acroosteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers. While PLS cases have been identified throughout the world, HMS has only been described among descendants of a religious isolate originally from Cochin, India. Parental consanguinity is a characteristic of many cases of both conditions. Although autosomal recessive transmission of PLS is evident, a more "complex" autosomal recessive pattern of inheritance with phenotypic influences from a closely linked modifying locus has been hypothesised for HMS. Recently, mutations of the cathepsin C gene have been identified as the underlying genetic defect in PLS. To determine if a cathepsin C mutation is also responsible for HMS, we sequenced the gene in aVected and unaVected subjects from the Cochin isolate in which both the PLS and HMS phenotypes appear. Here we report identification of a mutation of cathepsin C (exon 6, 2127A→ G) that changes a highly conserved amino acid in the cathepsin C peptide. This mutation segregates with HMS in four nuclear families. Additionally, the existence of a shared common haplotype for genetic loci flanking the cathepsin C gene suggests that aVected subjects descended from the Cochin isolate are homozygous for a mutation inherited "identical by descent" from a common ancestor. This finding supports simple autosomal recessive inheritance for HMS in these families. We also report a mutation of the same exon 6 CTSC codon (2126C→T) in a Turkish family with classical PLS. These findings provide evidence that PLS and HMS are allelic variants of cathepsin C gene mutations. (J Med Genet 2000;37:88-94)

The secretion of prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL‐1β), and interleukin 6 (IL‐6) by adherent mononuclear cells (AMNC) from 28 patients with early‐onset periodontitis was studied. The early onset‐periodontitis patients consisted of 12 patients with localized juvenile periodontitis (LJP) and 16 patients with severe generalized periodontitis (SGP). The AMNC responses to different concentrations of lipopolysaccharide (LPS) (E. coli) were determined in these 28 patients and compared to 14 healthy controls. Mediator levels in the supernatant were measured using radioimmunoassays for PGE2, IL‐1β, and IL‐6 determination and an enzyme linked immunosorbent assay for TNFα levels. The mean age of the patients was 19.9 years for the LJP group, 30.4 years for SGP, and 28.0 years for the controls. The mean number of teeth per patient with attachment loss of >6 mm was 4.75 in the LJP patients and 17.3 in the SGP group. In the absence of LPS, LJP AMNC secreted significantly more PGE2 than unstimulated control or SGP AMNC, while similar baseline amounts of IL‐1β, IL‐6, and TNFα were secreted by AMNC from the 3 patient groups. LPS stimulation resulted in the dose‐dependent secretion of significantly higher levels of PGE2 by LJP AMNC compared to SGP AMNC which in turn secreted significantly more than controls. TNFα secretion by LJP monocytes was significantly greater than the SGP and the control groups while IL‐1β secretion by the SGP AMNC was depressed compared to the other two patient groups. No significant difference in IL‐6 secretion was noted among the 3 patient groups. These data suggest that the AMNC from the peripheral blood from each of the 3 patient groups differ considerably in their capacity to secrete inflammatory mediators. It is not clear as to whether these intergroup differences in systemic AMNC responsiveness represent an intrinsic or acquired difference in LPS responsiveness. J Periodontol 1994;65:139–146.

The association between diabetes mellitus and periodontal disease has long been discussed, with conflicting conclusions. On the one hand, numerous reports indicate a high prevalence of periodontal disease in diabetics compared to healthy controls, while others fail to show such a relationship. Clarification of this dilemma has been occurring as the diagnostic criteria for periodontal disease destruction improve and the number and size of the populations surveyed grow. This review is based on a selective review of the literature from the present decade. To date, based mainly on an extensive study of the Pima Indians who have an extremely high incidence of non-insulin-dependent diabetes mellitus (NIDDM), it seems to be clear that patients with NIDDM have a higher prevalence and severity of periodontal disease destruction than non-diabetics in the same population. However, it must be borne in mind that these data are for a special population. Studies on patients with insulin-dependent diabetes mellitus (IDDM) indicate results similar to those found in studies on NIDDM. There is an increase in prevalence and severity of periodontitis compared to controls. For both IDDM and NIDDM, there does not appear to be any correlation between the prevalence or the severity of periodontal disease and the duration of diabetes. Well-controlled diabetic patients as measured by blood glycated hemoglobin levels have less severe periodontal disease than poorly controlled diabetics. The principles of treatment of periodontitis in diabetics are the same as those for non-diabetic patients and are consistent with our approach to all high-risk patients who have already developed periodontal disease. The major efforts should be directed at the prevention of periodontitis in patients at risk of developing diabetes. Another important clinical question relates to the influence of periodontal disease on the control of the diabetic state. Here again the literature is unclear; however, a recent development suggests that effective control of periodontal infection in patients with diabetes reduces the level of advanced glycosylation end products in the serum. If future studies can confirm this effect, then periodontal infection control must be considered an integral part of diabetic control.

Septic shock results from excessive stimulation of host immune cells, particularly monocytes and macrophages, by lipopolysaccharide (LPS) released from gram-negative bacteria. Macrophage-derived cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1 beta), have been identified as central mediators in the pathogenesis of septic shock and the resultant mortality. Therefore, these cytokines were targets for experimental therapy for septic shock. Because of tetracycline's ability to intervene in cellular mechanisms involved in cytokine secretion, we tested the effect of tetracycline on LPS-induced septic shock and inflammatory lesions in mice. Tetracycline was found to protect mice against LPS-induced lethality and to abolish clinical signs of LPS-induced inflammatory lesions. This protection correlates with tetracycline's ability to reduce LPS-induced TNF-alpha levels in serum. Furthermore, tetracycline was found to inhibit LPS-induced TNF-alpha and IL-1 beta secretion, but not cytokine mRNA accumulation, in human monocytes in vitro. The results presented here suggest that tetracycline is a potent drug for LPS-induced pathology and that its mechanism of action involves blockage of posttranscriptional events of cytokine production.

Periodontal destruction measures are significantly correlated with CAD severity, whereas periodontal infectious measures are significantly associated with clinical cardiac status.