Bidirectional relationship between diabetes and periodontal disease: review of evidence.
Periodontal disease (PD) and diabetes mellitus (DM) hold a consistent relationship. DM not only There is a bidirectional relationship between DM and PD. PDF | On Jul 16, , Bilal Abdul Qayum Mirza and others published bidirectional relationship between diabetes and periodontal disease. Periodontitis is a common problem in patients with diabetes. The relationship between these 2 maladies appears bidirectional—insofar that the.
This results because insulin deficiency inhibits 6-desaturase enzyme activity. Increasing evidence suggests that lipid composition of membranes is a critical factor influencing cellular function.
The circulating monocytes of diabetic patients are hyper-responsive to LPS. This hyperresponsive monocytic phenotype is not associated with hyperglycemia  can exist independently of periodontitis  and may be related to hyperlipidemia.
MCP-1 acts as a major signal for the chemotaxis of mononuclear leukocytes. Monocytes play a significant part in periodontal tissue breakdown and are present in a greater concentration in patients with periodontitis. G6PDH activity has been found to be considerably decreased in neutrophils, macrophages, and lymphocytes isolated from diabetic rats.
In neutrophils in which G6PDH activity is deficient, phagocytosis, bactericidal ability, and superoxide production are impaired. Glutamine is involved in protein, lipid, and nucleotide syntheses, as well as in NADPH oxidase activity. Glutamine oxidation and glutaminase activity are reduced in neutrophils isolated from diabetic rats.
These free radicals derived from the mitochondrial cellular membrane, nucleus, lysosomes, peroxisomes, endoplasmic reticulum, and cytoplasm  are unstable, either donating unpaired electrons to other cellular molecules or extracting electrons from other molecules in order to achieve a stable milieu.
In low to moderate concentrations, they serve an important homeostatic function but in high concentrations, they are harmful and may contribute to the pathogenesis of chronic inflammatory diseases.
This oxidation results in cellular adhesion and increased production of cytokines and growth factors, resulting in stimulation of smooth muscle cell proliferation and causing an increase in the vessel thickness. In a glucose-rich environment, the reparative capacity of periodontal tissues is compromised.Periodontal Disease Systemic Effects Diabetes
Collagen synthesis, maturation, and general turnover are greatly affected in diabetes. The production of collagen and glycosaminoglycans is significantly reduced in high-glucose environments.
Bidirectional relationship between diabetes and periodontal disease: review of evidence.
Eventually, after chemical rearrangement, these glycated proteins are converted to a more stable, yet still reversible, glucose protein complex known as the amadori product. However, if hyperglycemia is sustained, the amadori products become highly stable and form AGE. Once formed, the AGE remains attached to proteins for its lifetime. Thus, even if hyperglycemia is corrected at this stage, the AGE in the affected tissues does not return to normal. The AGE thus formed accumulates in the periodontium, causing changes in the cells and extracellular matrix ECM components.
Collagen produced by fibroblasts under these conditions is susceptible to rapid degradation by matrix metalloproteinase MMP enzymes, such as collagenase, the production of which is significantly higher in DM.
AGE has an adverse effect on bone collagen at the cellular level and this may result in alterations in bone metabolism. Circulating LDL becomes cross-linked to this AGE-modified collagen and contributes to atheroma formation in the diabetic macrovasculature. In central and peripheral arteries, this enhances the macrovascular complications of diabetes. In smaller vessels, collagen in the vessels can lead to increased basement membrane thickness and compromised transport of nutrients across the membrane.
However, in diabetes, expression of RAGE is markedly increased.
Periodontal disease and diabetes mellitus. Bidirectional relationship.
These monocytes then penetrate the endothelium and migrate under intima layer where they ingest LDL in an oxidized state and become foam cells which are characteristic of atheromatous plaque. Once within the arterial media, these monocytes transform to macrophages releasing an array of proinflammatory cytokines and mitogenic factors causing muscle and collagen proliferation leading to thickening of the vessel walls. The effect on the endothelial cells is an increase in vascular permeability and thrombus formation.
In addition, oxidized LDL, elevated in many diabetic patients, also activates NFkB and may result in similar processes. Thus, alterations in lipid and protein metabolisms induced by the sustained hyperglycemia characteristic of diabetes may play a major role and provide a common link between all the classic complications of this disease. Thus, VEGF can be instrumental in the microvascular complications of diabetes.
Periodontal therapy eliminates the inflammation and helps to counteract insulin resistance. When there is an increase in energy requirement or increase in blood glucose levels, the excess glucose is loaded on the expressed insulin receptors and transported intracellularly.
Thus, excess glucose from circulation is removed and stored intracellularly mostly in adipose tissue. When the cells become resistant to action of insulin, there is an increase in insulin production by the pancreas to attempt and force glucose in the cells. This state of reduced responsiveness to normal circulating levels of insulin is "insulin resistance" and results in hyperinsulinemia. This results in hyperlipidemia, increased cholesterol CHand TRG as seen in individuals with insulin resistance.
An increase in circulating lipids leads to excessive lipid oxidation, deposits of these oxidized fractions on vessel wall, and atherosclerosis. This may reduce the risk for development of periodontitis. Additionally, in diabetic patients with periodontitis, reduction of serum lipids may improve the response to traditional periodontal therapy.
The aim of the traditional approach of periodontal therapy with scaling and root planing is to reduce the number of pathogens from the infected periodontium and disruption of the microbial colonies conducive for bacterial growth. The use of antibiotics can be adjunctive to the periodontal therapy. The lowering of blood glucose levels by insulin treatment has been reported to have a significant correlation with the improvement of phagocytosis capacity by neutrophils 39, The monocyte-macrophage function in diabetics has also been shown to be altered.
The monocytes isolated from the peripheral blood samples from diabetic patients have been shown to secrete significantly more prostaglandin E2 in response to bacterial endotoxins than those without the disease This hyperinflammatory response is thought to be a result of advanced glycosylation end products AGE and their receptors RAGE interaction on monocytes and macrophages. This hyperactive cell phenotype releases excessive cytokines, thus resulting in more connective tissue damage.
It has been proposed that AGE-RAGE binding on macrophage surfaces may alter macrophage phenotype, causing dysregulation of macrophage cytokine production and increased inflammatory tissue destruction and alveolar bone loss Furthermore, it has also been proposed that this altered scavenging function of macrophages is one of the reasons for the delayed wound healing in diabetics Raised levels of monocyte chemoattractant protein MCP -1 in periodontal tissue have been reported in diabetic patients as compared to healthy controls 48, MCP-1 acts as a major signal for the chemotaxis of mononuclear leukocytes.
The increased monocytic activity has been thought to be responsible for the greater periodontal breakdown in diabetic patients. Collagen is the major structural protein in the periodontium. The collagen synthesis, maturation, and general turnover are greatly affected in diabetes.
In diabetic patients, changes in collagen synthesis, maturation, and homeostatic turnover have been demonstrated. Under hyperglycemic conditions, the gingival fibroblasts produce decreased amounts of collagen and glycosaminoglycans This alteration in collagen synthesis has been shown to be reversed by administration of insulin to normalize plasma glucose levels In addition to reduced collagen and glycosaminoglycan synthesis, the newly formed collagen is…………… Periobasics: This is one of the most common complications in diabetic patients.
Increased levels of glucose in the GCF lead to hindering of fibroblast function during wound healing Figure The attachment and spreading of these cells are critical to wound healing and normal tissue turnover Growth factors are important for wound healing.
In the hyperglycemic state, the advanced glycosylation end products AGEs are formed. These affect the vasculature by stimulating arterial smooth muscle cell proliferation and increasing the thickness of the vessel wall. Abnormal cross-linkage of AGEs modified collagen in the basement membrane causes abnormal degradation of these proteins, leading to thickening of the basement membrane.
Studies have indicated an increase in pro-inflammatory cytokine levels in GCF in diabetic patients 58, which can be related to the above-stated action of AGEs.
As already stated, AGEs cross-link with basement membrane collagen and alter the vessel wall structure. The circulating low-density lipoproteins LDL becomes cross-linked to this AGE-modified collagen and contributes to atheroma formation. Furthermore, in small blood vessels, the cross-linking of AGEs with collagen fibers results in increased basement membrane thickness and compromised transport of nutrients across the membrane 59, AGEs are also associated with…………………….
Hyperglycemia increases oxidative stress, which contributes to the cellular and extracellular damage. In addition, antioxidant mechanisms are diminished in diabetic patients, which may further augment oxidative stress 66, The AGEs formed in the diabetic patient have been associated with enhanced oxidant stress 68, 69 and subsequent expression of endothelial vascular cell adhesion molecule VCAM -1 These changes further enhance the destructive process and contribute to the connective tissue destruction.
Effect on osteoblastic and osteoclastic function: Under normal conditions there is a critical balance between the osteoblastic and osteoclastic activity, maintaining the normal bone turnover.
[Diabetes and periodontitis: A bidirectional relationship].
However, in a hyperglycemic state, there is inhibition of osteoblastic cell proliferation and collagen production that result in reduced bone formation and diminished mechanical properties of the newly formed bone The effect of AGEs on osteoclast function is not completely clear.
Some studies have reported significant levels of osteoclasts and increased osteoclast activity in diabetic patientswhereas other studies have reported decreased bone resorption under similar conditions Gingivitis is the inflammation of gingiva with no attachment loss, whereas, in periodontitis, there is a loss of periodontal structures clinically evident as attachment loss.
The host-microbial interactions lead to the production of various chemical mediators which have local and systemic effects.
As both periodontal diseases and diabetes, especially type 2 diabetes, have major inflammatory components, the role of inflammatory mediators is important in the disease progression. The following mechanisms have been proposed to explain the effect of periodontal infection on diabetes mellitus, Micro-organisms involved in periodontal infection in diabetics: As we know that the bacteria involved in periodontitis are usually anaerobic Gram-negative bacteria.
They cause damage to periodontal tissues directly by releasing their virulence factors and indirectly by initiating the release of various inflammatory mediators by host immune cells These findings indicate that periodontal infections may lead to insulin resistance. The microbiological studies done on diabetic patients have not revealed any particular bacterial species which may be increased in number in these patients One study, done on periodontally involed type 1 diabetic and their non-diabetic healthy siblings staying together found no difference in their levels of Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Capnocytophaga species However, one study has reported significantly higher counts of Capnocytophaga species in periodontal pockets of diabetics as compared to periodontal pockets in healthy individuals Role of pro-inflammatory factors: As already stated, periodontal treatment has been associated with improved glycemic control and reductions in HbA1c levels The reason for the improved glycemic control is the reduction in the pro-inflammatory cytokine levels locally, and therefore reduced levels of these mediators in the circulation.
Both of these mediators are strong inducers of acute-phase proteins such as CRP, and both have been shown to impair intracellular insulin signaling 89, Under normal conditions when insulin binds to the insulin receptors on muscle and fat cells, a tyrosine residue of the cytoplasmic domain of the insulin receptor is autophosphorylated.