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GENERALIZED PARODONTITIS AND DIABETES MELLITUS TYPE 2: PATHOGENETIC ASPECT
OF COMORBIDITY (LITERATURE REVIEW)
Lenihevych A.
Ph.D. student Department of Dentistry Institute of postgraduate education Bogomolets National Medical University
Kiev
Abstract
Numerous epidemiological researches have shown a close link between parodontal disease and diabetes. Modern ideas about parodontal disease not only as a complication but also as a real risk factor for systemic diseases, including diabetes, require careful consideration of approaches to treatment and prevention of comorbidity pathology.
Keywords: generalized parodontal disease, generalized parodontitis, type 2 diabetes mellitus.
Parodontal disease is the most common dental pathology and one of the most difficult problems in dentistry [5]. Oral health researchers in adults have found that 75% of them aged 55-64 have signs of parodontitis (pocket depth >4 mm), and this figure rises to 82% among patients aged 75-84 [54]. At the same time, among the key determinants in the pathogenesis of chronic generalized parodontitis (CGD) today are metabolic and microcirculatory disorders [9].
More than 400 million people in the world suffer from diabetes mellitus (DM). Experts from the International Diabetes Federation predict that by 2045, about 693 million patients will have diabetes between the ages of 18 and 99 [24]. At the same time, type 2 DM, which develops as a result of impaired interaction of insulin with tissue cells, is described as a real epidemic of our time. Decreased insulin secretion, glucose utilization, or increased gluconeogenesis lead to hypergly-cemia and impaired carbohydrate, protein, and fat metabolism. It is recognized that patients with DM have
three times higher risk of parodontal disease compared to patients without endocrine pathology. At the same time, parodontal diseases on the background of DM are characterized by a clear tendency to chronicity of the pathological process and in 7% of cases become severe [22, 23, 25, 42]. According to Zheng et al. (2021), among 3092 patients with DM and 23494 of the control group, the overall prevalence of parodontitis was 67.8% in patients with diabetes (both types) and 35.5% in patients without diabetes. The depth of probing and the plaque index were significantly greater in DM [56]. According to some data, in patients with DM the risk of gingivitis and parodontitis increases by 2.5-3.5 times depending on the age and severity of DM [55]. Thus, according to Sima and Glogauer (2013), in patients with diabetes the intensity of parodontal lesions is higher than in the control group. The value of the complex parodontal index (CPI) in patients with diabetes is higher among patients of any age (3.4 - at the age of 3544 years, 3.8 - at 45-54 years, 4.1 - at 55-64 years ), while in the control group - 2.9, 3.1, 3.2, respectively [22]. Parodontitis is registered in 100% of cases with DM in last more than 10 years [57]. In a survey by Ge et al. (2021) was attended by 5,220 adults with a history of DM, of whom 3,064 - with type 2 DM. Statistics showed that the prevalence of moderate and severe parodontitis in type 2 DM was 10.57%. In the group of severe parodontitis 79.01% of patients were older than 65 years, 55.56% - patients smoked. With prolonged status of type 2 DM, the percentage of severe parodon-titis increased. Patients with type 2 diabetes and poor glycemic control accounted for 68.52% in the group with severe parodontitis, which was significantly higher than in the group with mild parodontitis (60.99%). According to the authors, among patients with type 2 DM, older age, male gender, smoking and poor glycemic control are associated with the severity of CGP [14].
The noted connection between parodontal disease and diabetes mellitus shifts dentistry beyond the private clinical discipline and creates a powerful pathophysio-logical basis for solving oral health problems in general medical practice [46]. The purpose of Siddiqi et al. (2020 was an assessment of the attitude of patients with DM towards two-way communication and the role of health professionals in providing recommendations on oral health (n = 241). Most (87.81%) participants had type 2 DM, while 11.76 % - type 1 DM, with the majority of participants (66.38%) reporting that the endo-crinologist had never asked for or examined their oral cavity or was interested in gum or tooth problems, and that 54% had never received any information about the two-way relationship between parodontal disease and DM. The authors emphasize the need for mutual assistance of doctors and dentists and consider each patient as a shared responsibility [47].
The study of the relationship between pathological changes in parodontitis and type 2 DM, diagnosed in 90% of patients with diabetes, has been the subject of numerous studies, which proved that not only systemic pathology affects the oral cavity, but also dental diseases affect course of the main pathology [1-3].
According to most authors, diabetes is associated with a decrease in bone density, inhibition of bone formation, which contributes to osteoporosis and osteolysis, which causes parodontal disease and tooth loss [5860]. Yes, according to Poudel et al. (2017), the mobility of teeth is indicated by 84% of patients with DM, bleeding gums - 96%, 92% of patients with DM have missing teeth. Unsatisfactory condition of the oral cavity was noted by 40% of respondents [48]. Bone damage in diabetes is due to the fact that low insulin levels reduce the activity of osteoblasts, cause metabolic acidosis, while increasing the activity of osteoclasts. The authors note the discrepancy between clinical and radiological symptoms of alveolar bone destruction: in moderate gingivitis observed marked resorption of bone tissue of the alveolar process, fix deep parodontal pockets (PD). It is established that the radiological sign of parodonti-tis in DM is diffuse osteoporosis with atrophy of bone tissue [61, 62].
In Ukraine, lesions of the oral cavity in DM, including CGP, are not officially recognized complications of diabetes. As a result, there are no standardized measures for early diagnosis, specific prevention and treatment of CGP [16].
According to the findings of many researchers, there is an awareness that not only the diagnosis of DM or its type has a negative impact on parodontal health, but rather the level (severity) of hyperglycemia is a determining factor [5]. It should be noted that the development of type 2 DM is accompanied by hyperllyce-mia, hyperlipidemia and immune dysfunction [33, 44, 45], ie similar processes involved in the pathogenesis of chronic parodontitis [44].
Several potential mechanisms have been proposed to explain the increased susceptibility to parodontal destruction among patients with DM. These include he-modynamic disorders and the development of angiopathies, disorders of cellular metabolism, immunological and neuroregulatory disorders, as well as chronic tissue damage by end products of enhanced glycosylation. Inflammatory response is considered a critical determinant in both the pathogenesis of parodontitis and DM, as bacteremia caused by parodontitis causes an increase in serum proinflammatory cytokines and reactive oxygen species, which is involved in the etiopathogenesis of DM and increased insulin resistance [12, 20,21].
The development of the inflammatory process in the parodontium, its generalization and chronicity are determined by the species and quantitative composition of the microflora of the oral cavity, as well as the state of the immune system altered by diabetic pathogenetic factors [28]. Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actino-mycetemcomitans, Porphyromonas endodontalis, Prevotella intermedia, Fusobacterium nucleatum/paro-donticum considered the main pathogens involved in the development of parodontitis [27]. The results of the study of the influx of parodontal pathogens in patients with CGP in association with type 2 DM have shown that the composition of the etiologically significant complex of these bacteria and their functions has a distinct originality [43]. It has been shown that in patients
with DM with parodontitis, microorganisms not characteristic of a healthy parodontium (eg, Enterobacter spp., Pseudomonas aeruginosa) were detected, reaching 35% [40, 41].
Patients with poorly controlled type 2 DM have an increased inflammatory response to the bacterial challenge of parodontitis. Hyperinflammatory response combined with impaired healing and wound healing enhances parodontal tissue destruction in these patients [18, 19]. Thus, elevated levels of proinflammatory mediators in poorly controlled diabetes lead to chronic inflammation, progressive tissue destruction and reduced tissue repair capacity [12].
The vascular concept of chronic parodontitis is the basis of the pathogenesis of diabetic parodontitis. The incidence of angiopathy (microcirculatory disorders) in diabetes reaches 68.0-91.3% [63]. However, in type 2 DM, parodontal vessels are affected earlier than vessels in other organs, and the severity of parodontitis is significantly related to the number of microvascular complications. However, the prevalence of parodontitis was not significantly related to the number of microvascular complications, but was associated with male gender, high glycated hemoglobin (HbAlC, >8.0%), older age (>40 years), longer duration of diabetes (>15 years) and fewer kept teeth (<25) [64]. The pronounced clinical symptoms of parodontitis in type 2 DM, especially in its decompensation, are explained by changes in vascular permeability and hemodynamic disorders, in which there are changes in the movement of fluid and proteins from blood into tissues. Wich DM in patients the stability of walls of capillaries of an oral cavity decreases, intensity of changes thus depends on duration of diabetes, that is, parodontal pathology at diabetes is a local display of primary diabetic angiopathy causing metabolic disturbances with development of dystrophic and atrophic changes of all parodontal complex components [64]. Jindal et al. (2015) emphasize that DM is characterized by generalized damage to the vessels of the microcirculatory tract, which is an important factor in the development of inflammation and determines the course of parodontitis and the subsequent prognosis of the disease [69].
Microangiopathy in diabetes leads to increased resorption of bone tissue, impedes the entry of micronu-trients and oxygen diffusion into parodontal tissue, which against the background of existing metabolic disorders further inhibits reparative processes in the alveolar bone [67]. At the same time, in patients with moderate CGP (n = 40) compared with the control group (n = 26) there is a significant increase in serum concentrations of D-dimer (10.5 times), factor Xlla (8.4 times), Willebrand factor (2 times), fibrinogen (64.8%) and antiplasmin (12.7%), as well as a decrease in an-tithrombin (17%). The identified changes confirm that patients with type 2 DM are characterized by severe en-dothelial dysfunction with a decrease in its barrier properties [66]. The consequence of the structural reorganization of vascular walls is focal hemorrhage, as well as inflammatory phenomena as a manifestation of reduced local immunity due to circulatory disorders [68].
Disorders of microcirculation and immune cell functions can be both primary (under the influence of
diabetes) and secondary (under the influence of the inflammatory process in the parodontium). The cause of inflammatory processes in the parodontium is xerostomia and secondary immunodeficiency [65]. Clinical symptoms of xerostomia Carda et al. (2006) found in 76.4% of patients with type 2 DM (n = 17) [38].
The most accurate indicator of the body's resistance is the protein content in saliva. In patients with diabetes, the level of protein is increased compared to somatically healthy patients, the level of protein increases as an indicator of inflammation [70]. The major proteins present in saliva (proline-rich proteins, hista-tines, cystatin, defensins, cathelicidin-LL37), and enzymes such as amylase (ptialin), peroxidase, and lyso-zyme are proven and potential biomarkers of disease, and studies of markers of dysfunction and slin protein expression in patients with DM is a promising tool for detecting parodontitis before the development of clinical symptoms [34]. For example, the level of matrix metalloproteinases (MMPs) -8 and -9 are considered promising markers of caries and parodontal disease [31].
Problems related to the identification of new biomarkers of parodontitis in saliva continue to be discussed [35, 36]. There was a significant decrease in ly-sozyme activity in mixed saliva in persons with decompensated DM, a-amylase and peroxidase activity; increase in viscosity, acidity, total protein, alkaline phosphatase activity, changes in microcrystal growth, decreased saliva mineralizing potential and phagocytic activity of oral neutrophils, increased sediment, changes in Ca and P content (Ca level increases, P -decreases), violation the Ca / P ratio [22, 37, 39].
An important role in the pathogenesis of parodontal disease is played by impaired cytokine regulation and synthesis of inflammatory mediators, especially interleukins (IL) -1p, -6, 12, -18, prostaglandin E2, TNF-a, matrix MMP-8, -9 and -13) and chemo-kines [49-51]. In CGP complicated by DM, pathogenet-ically significant changes in the immune status of the body are changes in the ratio of pro-inflammatory (TNF-a, IL-1P, IL-6) and anti-inflammatory (IL-4) cy-tokines, which helps maintain and chronic inflammation in parodontal tissues. In the process of developing inflammation of parodontal tissues and DM, there was an increase in the synthesis of pro-inflammatory cyto-kines [52, 53]. However, according to Abdellatif et al. (2021), there is an unclear link between IL polymorphism and parodontitis in patients with DM. The authors noted that some studies have shown that gene polymorphism (primarily IL-1P) exacerbates parodontitis in patients with type 2 DM, in others it is shown that IL-1P genes do not contribute to the progression of parodontitis in patients with type 2 DM, or have a low probability, the main factor that "controls" the occurrence and progression of parodontitis in patients with type 2 DM is poor routine oral hygiene [15].
There is growing evidence that type 2 DM precedes parodontal disease than vice versa [10,11]. In a systematic review by Wu et al. (2020) summarizes the results of a study of the bidirectional association of parodontitis and type 2 DM with a follow-up period of 2.6 to 20 years. However, well-controlled type 2 DM
did not increase the risk of parodontitis, and poorly controlled - significantly increased the incidence of parodontitis and its severity. Patients with type 2 DM had a 0.89 mm higher rate of clinical loss of attachment (CAL) than in the control group of patients without diabetes (DM-free group), PD was 0.61 mm deeper than in DM-free, and also, patients with type 2 DM had an average of 2.01 fewer teeth left than DM-free patients [8]. Compared with DM-free patients, the risk of alveolar bone damage is 11 times higher in uncontrolled diabetes [26].
Suzuki et al. (2021) analyzed data on 4625 removed teeth in 3750 patients. Among patients with DM, 55.4% had teeth removed due to periodontitis compared to 46.7% of patients in the DM-free group. Thus, DM is significantly associated with tooth extraction due to parodontitis [17]. Among those evaluated by Stoicescu et al. (2021) clinical parameters of oral plaque accumulation were significantly higher in patients with CGP (n = 182) and poor glucose control (74.2 ± 25.2 vs. 62.5 ± 28.7%), and mean values of PPD (3.78 ± 0.9 vs. 3.42 ± 0.8 mm) and CAL (4.5 ± 1.2 vs. 4.1 ± 1.2 mm). Areas with PPD >5 mm were more common among patients with HbAlc >7% compared with patients with HbAlc <7% (27.8 ± 6.2 vs. 23.4 ± 5.8%). The average number of remaining teeth was lower in patients with HbAlc >7% compared with patients with HbAlc <7% (18.5 ± 3.2 vs. 20.4 ± 4.1) [13].
The consensus report of the joint seminar EFP / AAP (2013) states that parodontal therapy after 3 months is associated with a decrease in HbA1C of approximately 0.4%, which is a clinical effect equivalent to the addition of a second drug to the pharmacological treatment of diabetes [4]. It has also been found that in patients with type 2 DM, periodontitis is associated with higher levels of HbA1C [7].
Thus, an analytical review of the results of numerous studies of cocmorbidity of generalized parodontitis and type 2 DM will prove the relationship between diabetes and the development of inflammatory and destructive changes in the parodontium. At the same time, against the background of DM, parodontal disease occurs earlier than in patients without endocrine pathology, have a more severe course and progress faster. Parodontal diseases in type 2 DM have a specific course due to metabolic, inflammatory disorders and systemic angiopathy. Analysis of the current literature suggests that screening for parodontal disease should be part of the clinical examination of patients with diabetes, and treatment of CGP will help improve not only the dental status of patients, but also glycemic control and reduce the number of diabetic complications.
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