Peculiarities of bone tissue metabolism in patients with acute otitis media with impared carbonhydrate metabolism
Abstract: Introductions: Relevance of the study is due to the unrecognized effect of carbohydrate metabolism disorders on bone tissue metabolism in patients with acute otitis media (AOM). Aim: to determine the peculiarities of bone tissue metabolism in patients with AOM caused by disorders of carbohydrate metabolism. Materials and methods: Our study included 73 patients aged 18 to 79 (29 males and 44 females) who were randomized into 4 groups according to the aim of the research: Group 1 – 17 patients with AOM, Group 2 … Show more
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The relevance of the study is due to the lack of data to determine the pathogenetic significance of cytokine profile specifics and correlation pleiades in patients with acute otitis media (AOM) on the background of disorders of glucose metabolism and dyslipidemia manifestations. The aim of our research: to determine the peculiarities of cytokine profile of peripheral blood in the amount of IL-4, IL-6 and TNF-α and to investigate the correlation pleiades in patients with AOM on the basis of glucose metabolism disorders with regard to the processes of glucose formation, dyslipidemia, and bone tissue metabolism. Materials and methods: We examined 73 patients with AOM aged 18 to 79 (29 males and 44 females), who were randomized into 4 groups.1 and 2 groups (comparison) (17 patients with acute AOM and 15 patients with AOM with paranasal sinus pathology in groups accordingly) and groups 3 and 4 (main groups) (20 patients with AOM with type 2 diabetes and 21 patients with AOM with glucose metabolism disorders accordingly). Apart from the clinical examination, all patients were tested for glucosylated hemoglobin (HbAlc), IL-4, IL-6, TNF-α and low-density lipoproteins (LDL). The pathogenetic significance of the observed changes was assessed by determining the correlations of the indices given, taking into account the previously established metabolism of bone tissue in the amount of parathormone, osteocalcin, and calcium. Results of the study and discussion: In patients with acute otitis media with impaired glucose metabolism there was a significant (p˂0.001) increase in the pool of proinflammatory cytokines IL-6 (10.26±0.46 pkg/ml and 10.94±0.5 pkg/ml in groups 3 and 4 accordingly) and TNF-α (11.05±0.5 pkg/ml and 9.7±0.5 pkg/ml accordingly in groups 3 and 4).The increase in the level of TNF-α was 1.9 times greater in patients with type 2 diabetes and 1.7 times greater in patients with transient disorders of glucose metabolism, in relat ion to the increase in the amount of IL-6 (1.1 to 1.3 times in groups 3 and 4, respectively).The amount of antiinflammatory cytokine IL-4 was within the reference norms for the methodology used, but was consistent ly lower in patients with glucose metabolism disorders (7.27±0.2 pkg/ml and 7.79±0.2 pkg/ml in groups 3 and 4 respectively, p˂0,001).We also found a significant (p˂0,001) increase in low density lipoproteins as a manifestation of dyslipidemia in patients with AOM against the background of impaired glucose metabolism 1.8 times in group 3 patients (4,6±0,25 mmol/l) and 1.7 times in group 4 patients (4,27±0,2 mmol/l). Influence of carbohydrate metabolism disorders on formation of cytokine profile and significance of dyslipidemia in pathogenesis of AOM is confirmed by the determined authenticity of variations in glucose content, HbAlc and these indices in patients in the main groups (groups 3 and 4) and the comparison groups (groups 1 and 2) due to the absence of differences in the data between groups 1 and 2 and 3 and 4 (p˃0,05). The study of the correlat ion pleiades of the indices with the markers of bone tissue metabolism revealed the inimitability of their presence, number and strength in patients in groups 1-2 due to the lack of correlation with indicators of glucose and HbAlc, IL-6, LDL and parathormone, which may indicate that in these patients only the mucous membrane of the middle ear is involved in the process. In patients with AOM with type 2 diabetes mellitus, multiple interactions of moderate strength, both direct (glucose – TNF-α, IL-6; HbAlc – LDL, TNF-α, IL-6; parathormone – IL-6, LDL; LDL – TNF-α) and inverse (calcium – TNF-α, LDL; IL-6 – calcium, IL-4), with the effect on bone tissue metabolism were found. In patients of group 4, the presence and strength of the interrelationships were similar to the above on the background of type 2 diabetes with a decrease in their number and a strong direct correlation of HbAlc – parathormone, IL-6; parathormone – IL-6, LDL; LDL – IL-6. Conclusions: Blood cytokine profile in patients with acute otitis media with impaired glucose metabolism is characterized by a significant increase in the pool of proinflammatory cytokines ІL-6 and TNF-α, a decrease in the level of anti-inflammatory cytokine ІL-4 in dyslipidemia by indicators of a significant increase in LDL. Multiple interrelationships of the studied indicators in patients with AOM on the background of type 2 diabetes characterize the complex proinflammatory background with an impact on the indicators of bone tissue metabolism. Similar interrelations on the background of transient disorders of glucose metabolism indicate their importance in the pathogenesis of a particular AOM, which is also confirmed by the validity of differences in the indicators and observed correlations in patients of groups 1-2 and 3-4. Taking into account the presence and peculiarities of the influence of any disorders of carbohydrate metabolism, including transient ones, is valuable for increasing the efficiency of diagnosis and treatment of AOM in adults.
The relevance of the study is due to the lack of data to determine the pathogenetic significance of cytokine profile specifics and correlation pleiades in patients with acute otitis media (AOM) on the background of disorders of glucose metabolism and dyslipidemia manifestations. The aim of our research: to determine the peculiarities of cytokine profile of peripheral blood in the amount of IL-4, IL-6 and TNF-α and to investigate the correlation pleiades in patients with AOM on the basis of glucose metabolism disorders with regard to the processes of glucose formation, dyslipidemia, and bone tissue metabolism. Materials and methods: We examined 73 patients with AOM aged 18 to 79 (29 males and 44 females), who were randomized into 4 groups.1 and 2 groups (comparison) (17 patients with acute AOM and 15 patients with AOM with paranasal sinus pathology in groups accordingly) and groups 3 and 4 (main groups) (20 patients with AOM with type 2 diabetes and 21 patients with AOM with glucose metabolism disorders accordingly). Apart from the clinical examination, all patients were tested for glucosylated hemoglobin (HbAlc), IL-4, IL-6, TNF-α and low-density lipoproteins (LDL). The pathogenetic significance of the observed changes was assessed by determining the correlations of the indices given, taking into account the previously established metabolism of bone tissue in the amount of parathormone, osteocalcin, and calcium. Results of the study and discussion: In patients with acute otitis media with impaired glucose metabolism there was a significant (p˂0.001) increase in the pool of proinflammatory cytokines IL-6 (10.26±0.46 pkg/ml and 10.94±0.5 pkg/ml in groups 3 and 4 accordingly) and TNF-α (11.05±0.5 pkg/ml and 9.7±0.5 pkg/ml accordingly in groups 3 and 4).The increase in the level of TNF-α was 1.9 times greater in patients with type 2 diabetes and 1.7 times greater in patients with transient disorders of glucose metabolism, in relat ion to the increase in the amount of IL-6 (1.1 to 1.3 times in groups 3 and 4, respectively).The amount of antiinflammatory cytokine IL-4 was within the reference norms for the methodology used, but was consistent ly lower in patients with glucose metabolism disorders (7.27±0.2 pkg/ml and 7.79±0.2 pkg/ml in groups 3 and 4 respectively, p˂0,001).We also found a significant (p˂0,001) increase in low density lipoproteins as a manifestation of dyslipidemia in patients with AOM against the background of impaired glucose metabolism 1.8 times in group 3 patients (4,6±0,25 mmol/l) and 1.7 times in group 4 patients (4,27±0,2 mmol/l). Influence of carbohydrate metabolism disorders on formation of cytokine profile and significance of dyslipidemia in pathogenesis of AOM is confirmed by the determined authenticity of variations in glucose content, HbAlc and these indices in patients in the main groups (groups 3 and 4) and the comparison groups (groups 1 and 2) due to the absence of differences in the data between groups 1 and 2 and 3 and 4 (p˃0,05). The study of the correlat ion pleiades of the indices with the markers of bone tissue metabolism revealed the inimitability of their presence, number and strength in patients in groups 1-2 due to the lack of correlation with indicators of glucose and HbAlc, IL-6, LDL and parathormone, which may indicate that in these patients only the mucous membrane of the middle ear is involved in the process. In patients with AOM with type 2 diabetes mellitus, multiple interactions of moderate strength, both direct (glucose – TNF-α, IL-6; HbAlc – LDL, TNF-α, IL-6; parathormone – IL-6, LDL; LDL – TNF-α) and inverse (calcium – TNF-α, LDL; IL-6 – calcium, IL-4), with the effect on bone tissue metabolism were found. In patients of group 4, the presence and strength of the interrelationships were similar to the above on the background of type 2 diabetes with a decrease in their number and a strong direct correlation of HbAlc – parathormone, IL-6; parathormone – IL-6, LDL; LDL – IL-6. Conclusions: Blood cytokine profile in patients with acute otitis media with impaired glucose metabolism is characterized by a significant increase in the pool of proinflammatory cytokines ІL-6 and TNF-α, a decrease in the level of anti-inflammatory cytokine ІL-4 in dyslipidemia by indicators of a significant increase in LDL. Multiple interrelationships of the studied indicators in patients with AOM on the background of type 2 diabetes characterize the complex proinflammatory background with an impact on the indicators of bone tissue metabolism. Similar interrelations on the background of transient disorders of glucose metabolism indicate their importance in the pathogenesis of a particular AOM, which is also confirmed by the validity of differences in the indicators and observed correlations in patients of groups 1-2 and 3-4. Taking into account the presence and peculiarities of the influence of any disorders of carbohydrate metabolism, including transient ones, is valuable for increasing the efficiency of diagnosis and treatment of AOM in adults.
Relevance. Relevance of the research is caused by the clinical necessity to increase efficiency of diagnostics and treatment of acute otitis media (AOM) from the modern positions personalized medicine and the feasibility of statistical verification of the validity of the hypothesis about the influence of glucose metabolism disorders on the formation of clinical and pathogenetic features of acute otitis media in adults. Objective. To carry out statistical verification of the hypothesis about the influence of carbohydrate metabolism disorders on the complicated course of AOM on the basis of cluster analysis and to determine its informativity. Materials and methods. The cluster analysis included 73 with AOM. The 1 group (n=17) - patients with AOM; 2 group (n=15) - patients with AOM with presence of the sinus pathology; 3 group (n=20) - patients with AOM due to type 2 diabetes mellitus (DM2); 4 group (n=21) - patients with AOM due to transient glucose metabolism disorders. Apart from the clinical examination, all patients were tested for HbAlc, parathormone, osteocalcin, total calcium, IL-4, IL-6, FNP-α, and low-density lipoproteins (LDL). Cluster analysis on the basis of laboratory indicators was performed by the hierarchical method using the iterative algorithm of k-means and prior standardization of the data. Result. The hypothesis was tested at the level of stratification of patients into 4 and 2 clusters. In the first case, 28.8 %, 31.5 %, 15.6 %, and 24.6 % of the total number of patients were included in clusters I, II, III, and IV. Patients with AOM due to impaired glucose metabolism were predominantly in clusters I and II, comprising 51.2 % and 69.5 % of the cluster contingent respectively, while DM2 prevailed in cluster I and transient glucose metabolism disorders in cluster II (61.9 % and 62.5 % accordingly), 72.7 % and 94.4 % of patients with AOM without impaired glucose metabolism were stratified in clusters III and IV. The analysis of laboratory indicators using the k-means algorithm showed a general tendency for the increase in glucose, HbAlc, parathormone, TNF-α and LDL in patients with AOM in clusters I and II with increased levels of osteocalcin, calcium and IL-4 in patients in clusters III and IV with the presence of a significant difference (p˂0.05). At the level of patients' grouping into two clusters, cluster I included 41.9 % of the total number of patients due to the presence of all glucose metabolism disorders (of these, DM2 occurred in 57.6 % and transient glucose metabolism disorders in 43.3 %). The II cluster (58.9 % of patients) included all patients with AOM without impaired glucose metabolism, accounting for 74.4 % of its structure, and 25.6 % of patients with impaired glucose metabolism (6.97 % for DM2 and 18.6 % for transient impairments). The k-means algorithm revealed a clear and reliable distribution of clusters for all 9 studied indicators, which resulted in an increase in glucose content, HbAlc, levels of parathormone, IL-6, TNF-α and LDL and decreased osteocalcin, calcium and IL-4 in I cluster compared to II. Differences in the indicators at the group-group levels, group-cluster and cluster-cluster revealed a sufficient difference in the first and third cases (with the exception of osteocalcin) and their absence at the group-cluster level (with the exception of parathormone for cluster I, p˂0.01 and glucose and HbAlc for cluster II, p˂0.05). Conclusion. The cluster analysis was informative and confirmed the hypothesis about the influence of glucose metabolism disorders on peculiarities of AOM pathogenesis in adults according to laboratory indices. The principal importance of the presence or absence of impaired glucose metabolism in patients with AOM is confirmed by stratification of patients into two clusters. Thus, all patients without glucose metabolism disorders were included in one (II) cluster. The contingent of patients with impaired glucose metabolism was not homogeneous, with cluster I comprising only patients with impaired glucose metabolism, but 15 % of patients with DM2 and 38.1 % of patients with transient disorders were in cluster II. Therefore, to improve the quality of diagnostics of complicated course of acute otitis media on the basis of glucose metabolism disorders it is necessary to supplement the laboratory indicators with informative clinical criteria. Parathormone level, as well as the combination of IL-6, TNF-α and LDL levels can be used as a marker of impaired glucose metabolism.
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