scholarly journals Distinguishable Immunologic Characteristics of COVID-19 Patients with Comorbid Type 2 Diabetes Compared with Nondiabetic Individuals

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ruxing Zhao ◽  
Yujing Sun ◽  
Yongyuan Zhang ◽  
Weili Wang ◽  
Shouyu Wang ◽  
...  

Background. COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. Methods. We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. Results. Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group ( p < 0.05 ). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. Conclusions. The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D.

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yonghuan Bian ◽  
Changhao Liu ◽  
Zhaojiang Fu

Abstract Background Our study attempted to observe the value of periodontal curettage combined with root planing on moderate-to-severe chronic periodontitis in patients with type 2 diabetes. Methods There involved 72 patients with type 2 diabetes mellitus complicated with moderate-to-severe chronic periodontitis who were diagnosed and treated in our hospital from January 2019 to December 2019. The patients enrolled were randomly divided into four groups using a computer-generated table: root planing and periodontal curettage combined group (n = 18), root planning group (n = 18), periodontal curettage group (n = 18) and cleansing group (n = 18). Blood glucose, plaque index (PI), gingival index (GI), probing depth (PD), attachment loss (AL), serum levels of inflammatory factors (Tumor Necrosis Factor Alpha [TNF- α] and hypersensitive C-reactive protein [hs-CRP]) were observed before and after treatment. The collecting dates were analyzed by the chi-square χ 2 test, repeated measurement analysis of variance, or t-test according to different data types and research objectives. Results Before treatment, there was no significant difference in PI, GI, PD and AL among the four groups (P> 0.05), while after 3-month treatment, the levels of PI, GI, PD and AL in the combined group were lower than those in the root planing group, periodontal curettage group and cleansing group, with both root planing group and periodontal curettage group significantly lower than cleansing group (P< 0.05). The fasting blood glucose, 2-h postprandial blood glucose and glycosylated hemoglobin in the combined group, root planing group, periodontal curettage group and cleansing group were significantly lower than those before treatment (P < 0.05). Before treatment, there was no significant difference in TNF- α and hs-CRP among the four groups (P> 0.05), but the levels of TNF- α and hs-CRP in the four groups decreased significantly after 3-month treatment (P< 0.05). The levels of TNF- α and hs-CRP in the combined group were lower than those in the root planing group, periodontal curettage group and cleansing group, and those in the root planing group and periodontal curettage group were significantly lower than those in the cleansing group (P< 0.05). Conclusion The combination therapy of periodontal curettage and root planing exerted beneficial effects on moderate-to-severe chronic periodontitis in patients with type 2 diabetes mellitus, which holds the potential to maintain the level of blood glucose and improve the quality of life of the patients.


2020 ◽  
Vol 15 (1) ◽  
pp. 364-372 ◽  
Author(s):  
Jie Li ◽  
Haiyan Shangguan ◽  
Xiaoqian Chen ◽  
Xiao Ye ◽  
Bin Zhong ◽  
...  

AbstractDiabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima–media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group (n = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group (n = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.


2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Mina Davari ◽  
Reza Hashemi ◽  
Parvin Mirmiran ◽  
Mehdi Hedayati ◽  
Shamim Sahranavard ◽  
...  

Abstract Background and objectives NF-kB, SIRT1 and systemic inflammation factors including hs-CRP, IL-6 and TNF-α accelerate atherosclerosis pathogenesis. Our purpose was to evaluate the effect of daily supplementation of three-gram cinnamon on plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α among type 2 diabetes patients. Subjects and methods A randomized, double blind, and controlled clinical trial was performed with 44 adult patients who were 25 to 70 years old with type 2 diabetes, randomized to two intervention (n = 22) and control (n = 22) groups differing by daily three grams cinnamon supplementation and placebo for 8 weeks, respectively. The plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α were measured by ELISA assay at the beginning and end of the study. Results After 8-week intervention, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) ended up the trial. It was not observed significant difference in levels of hs-CRP (P = 0.29), TNF-α (P = 0.27), IL-6 (P = 0.52), and Sirtuin-1 (P = 0.51) in between group comparison. While, the result showed significant difference in levels of NF-kB (P = 0.02) between groups. As well as, in among group comparison, there was not observed significant differences except in hs-CRP (P = 0.008) in placebo group. Conclusions This study elucidated that cinnamon supplementation has no beneficial effects in reduction of NF-kB, SIRT1, hs-CRP, IL-6 and TNF-α levels in type 2 diabetes patients which have a considerable role in development of atherogenesis.


Biomarkers ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Shadia A. Fathy ◽  
Mohamed R. Mohamed ◽  
Mohamed A. M. Ali ◽  
Ashraf E. EL-Helaly ◽  
Abdulnabi T. Alattar

2019 ◽  
Vol 6 (2) ◽  
pp. 20
Author(s):  
Jun X ◽  
Yanan Z ◽  
Zhijie C ◽  
Zhihui D ◽  
Danhua S ◽  
...  

Objective: To explore the relationship between serum plasminogen activator inhibitor (PAI-1) level and Type 2 Diabetes Mellitus (T2DM) accompanied by overweight or obesity by observing not only the changes of PAI-1 level in T2DM patients with overweight or obesity, but also glucose and lipid metabolism related indicators, the changes of the inflammatory cytokines secreted by adipocytes, and then making an analysis on the correlation to PAI-1.Methods: 36 cases of healthy examinees were selected as normal control group (NC group), and the experimental group can be divided into T2DM group (54 cases), Overweight/Obesity group (35 cases) and T2DM + Overweight/Obesity group (48 cases). Glucose and lipid metabolism related indicators such as fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbA1c), fasting insulin (FINS), insulin resistance index (IR), body weight index (BMI) and inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and PAI-1 were observed and compared between groups, and then made an analysis to explore the correlation of these factors to PAI-1.Results: (1) Compared with NC group, the levels of FBG, HbA1c, FINS and IR were increased in T2DM group, and the difference was of statistical significance. However, there was no statistically significant difference in TG, TC, LDL-C and BMI between NC group and T2DM group; the levels of FINS, IR, TG, LDL-C, TC and BMI were elevated in Overweight/Obesity group, and the difference was of statistical significance. However, there was no statistically significant difference in FBG and HbA1c; the levels of FBG, HbA1c, FINS, IR, TG, LDL-C, TC and BMI were up-regulated in T2DM + Overweight/Obesity group, and the difference was of statistical significance. Compared with T2DM group, the levels of TG, TC, LDL-C and BMI were increased in Overweight/Obesity group, and the difference was of statistical significance, however, the levels of FBG, HbA1c, FINS and IR were decreased, and the difference was statistically significant; The levels of FINS, IR, TG, TC, LDL-C and BMI were elevated in T2DM + Overweight/Obesity group, and the difference was of statistical significance, however, there was no statistically significant difference in FBG and HbA1c. Compared with Overweight/Obesity group, the levels of FBG, FINS, IR, HbA1c and LDL-C were increased in T2DM + Overweight/Obesity group, and the difference was of statistical significance. However, the difference in TG, TC and BMI was not statistically significant. (2) Compared with NC group, the levels of IL-6, TNF-α and PAI-1 were increased in T2DM group, Overweight/Obesity group and T2DM + Overweight/Obesity group, and the difference was statistically significant. Compared with T2DM group, the levels of IL-6 and TNF-α were elevated in Overweight/Obesity group, and the difference was of statistical significance, but there was no statistically significant difference in PAI-1; the levels of IL-6, TNF-α and PAI-1 were up-regulated in T2DM + Overweight/Obesity group, and the difference was statistically significant. Compared with Overweight/Obesity group, there was no statistically significant difference in IL-6 and TNF-α between T2DM + Overweight/Obesity group and Overweight/Obesity group, but the level of PAI-1 was increased in T2DM + Overweight/Obesity group, and the difference was of statistical significance. (3) Multivariate Logistic Regression Analysis showed that HbA1c, IR, TG, BMI, IL-6 and TNF-α were independently associated with the level of PAI-1 (all p < .05).Conclusions: (1) The level of PAI-1 is higher in type 2 diabetes mellitus patients with overweight or obesity than that in patients only with type 2 diabetes mellitus, and it is one of causes that result in vascular complications. (2) The increase in the level of PAI-1 is considered to be associated with IL-6 and TNF-α secreted by adipocytes.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244806
Author(s):  
Huiyuan Zhang ◽  
Yameng Zhang ◽  
Xiaochun Chen ◽  
Juhong Li ◽  
Ziyang Zhang ◽  
...  

Objective To analyze the effect of statins on cytokines levels in gingival crevicular fluid (GCF) and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Methods Systemically healthy controls (C group, n = 62), T2DM patients not taking statins (D group, n = 57) and T2DM patients taking statins (S group, n = 24) were recruited. In each group, subjects (40–85 years) were subclassified into the h (periodontal health)group, the g (gingivitis)group or the p (periodontitis) group according to different periodontal conditions. 17 cytokines in gingival crevicular fluid (GCF) and saliva samples of each subject were measured utilizing the Luminex technology kit. Further, HbA1c (glycated hemoglobin), FPG (fasting plasma glucose), PD (probing depth), CAL (clinical attachment level), BOP (bleeding on probing), GI (gingival index) and PI (periodontal index) were recorded. Data distribution was tested through the Shapiro-Wilk test, upon which the Kruskal-Wallis test was applied followed by Mann-Whitney U test and Bonferroni’s correction. Results Levels of IFN-γ, IL-5, IL-10 and IL-13 in the saliva of the Dh group were significantly lower than those in the Ch group, while factor IL-4 was higher (p<0.05). Levels of MIP-3α, IL-7 and IL-2 in GCF of the Dh group were considerably higher than those in the Ch group (p<0.05), while that of IL-23 was considerably lower. Compared with the Cg group, levels of IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly lower in the saliva of the Dg group (p<0.05). Lower levels of IFN-γ, IL-5 and IL-10 were detected in the Sg group than those in the Cg group (p<0.05). At the same time, levels of IL-1β, IL-6, IL-7, IL-13, IL-17, IL-21 and MIP-3α in the gingival crevicular fluid of the Sg group were lower in comparison with the Dg group. In addition, lower levels of IL-4 and higher levels of IL-7 in GCF were identified in the Dg group than those in the Cg group, while in the Sg group, lower levels of IL-4, MIP-1αand MIP-3αwere observed than those in the Cg group (p<0.05). Lower levels of IFN-γ, IL-6, IL-10, IL-13 and I-TAC were found in the Sp group compared with those in the Cp group. The IFN-γ, IL-6 and IL-10 levels were lower in the Dp group than those in the Cp group (p<0.05). Meanwhile, in the Sp group, lower levels of pro-inflammatory factors IFN-γ, IL-1β, IL-2, IL-6, IL-7, IL-21 and TNF-α, in addition to higher levels of anti-inflammatory factors IL-4 and IL-5 in gingival crevicular fluid, were identified than those in the Dp group. Higher levels of IFN-γ,IL-1β,IL-2,IL-7,IL-21 and TNF-α and a lower level of IL-5 in the Dp group were identified than those in the Cp group (p<0.05). Moreover, statins were able to substantially reduce PD in T2DM patients with periodontitis, indicating an obvious influence on the levels of cytokines secreted by Th1 cells, Th2 cells and Th17 cells, as revealed by PCA (principal component analysis). Conclusion Statins are associated with reduced PD and cytokines levels in the GCF and saliva of T2DM patients with periodontitis.


2018 ◽  
Vol 15 (6) ◽  
pp. 571-575 ◽  
Author(s):  
Ja Young Jeon ◽  
Kyoung Hwa Ha ◽  
Seung Jin Han ◽  
Hae Jin Kim ◽  
Kwan-Woo Lee ◽  
...  

Introduction: We examined whether circulating adiponectin levels are associated with further cardiovascular events in patients with type 2 diabetes. Methods: Between December 2004 and February 2005, 349 patients with type 2 diabetes were enrolled and followed-up until December 2015. Blood levels of total, middle-molecular weight and high-molecular weight adiponectin were measured at baseline. The primary composite outcome was the occurrence of the following events: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina and heart failure. Results: During a median follow-up of 9 years, cardiovascular events occurred in 14% of patients (50/349, 1.9% per year). Median blood levels of total, middle-molecular weight and high-molecular weight adiponectin were 4.8, 3.2 and 1.8 μg/mL, respectively. The cumulative incidence of cardiovascular events was not significantly different between the three groups based on total, middle-molecular weight, high-molecular weight or high-molecular weight/total adiponectin. After adjustment for potential confounding factors, blood adiponectin levels were positively associated with an increased number of cardiovascular events, but between tertiles, there was no significant difference. Conclusion: This observational cohort study suggested that blood adiponectin levels are not related to further cardiovascular events in patients with type 2 diabetes.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Fatima El-Tahir ◽  
Ali Moustafa Shendi Mohamed ◽  
Marwan Elgohary ◽  
Asmaa Mohammed Esh ◽  
Adel Ghorab

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases worldwide. The development of DKD includes immunologic and inflammatory mechanisms which involve activation of the innate immune system and participation of inflammatory cytokines such as tumor necrosis factor (TNF)-α. Chemerin is an adipokine that has been suggested to be related to inflammation and has been correlated with the development of diabetic complications.We aimed to explore the potential links between chemerin, inflammation and the development of DKD in patients with type 2 diabetes mellitus (DM). Method The study population included 94 subjects: 84 patients with type 2 DM (89.4%), classified into 3 groups according to the 24 hr urinary albumin, and 10 normoalbuminuric non-diabetic controls (10.6%). Demographic, clinical and analytical data, and chemerin and TNF-α levels were collected. Results A total of 84 diabetic patients were enrolled, 32 males (38.1%) and 52 females (61.9%), mean age 57.9±10.7 years. They were divided into 3 groups: 14 with normalbuminuria, 27 with microalbuminuria, and 43 with macroalbuminuria (24 h urinary albumin &lt;30, 30-300 and &gt;300 mg/dl respectively). Chemerin levels increased significantly with the rise in albuminuria (control: 21.3 (10.8 –180), normoalbuminuria: 794 (556.9-1066), microalbuminura: 1155.5 (718 – 1877) and macroalbuminuria: 1619 (705 – 8067) ng/ml; p&lt; 0.001, Kruskal Wallis test), yet with no significant difference between the control and normoalbuminuria groups. Serum TNF-α was significantly elevated in macroalbuminuria compared to control groups (p=0.017) with no significant difference between normoalbuminuria, microalbuminuria and macroalbumenuria groups (control: 77.85 (59 – 124.7), normoalbuminuria: 85.15 (59-146), microalbumenuria: 89 (68 – 180) and macroalbuminuria: 100 (66 – 556) pg/ml) (Figure). Among the diabetics, a significant association was evident between serum chemerin and serum TNF-α (r= 0.84; p&lt;0.001). Both biomarkers were significantly associated with the inflammatory markers ESR and CRP, serum creatinine, BUN, 24 hour urine albumin, HbA1c, and diabetes duration and negatively with eGFR and serum albumin (p&lt;0.05). On linear stepwise regression analysis, chemerin was significantly associated with TNF-α (unstandardized β 9.954, p&lt;0.001) and ESR (unstandardized β 19.596, p&lt;0.001); and TNF-α was significantly correlated with chemerin (unstandardized β 0.059, p&lt;0.001), 24 hour urine albumin (unstandardized β 0.004, p&lt;0.001) and HbA1c (unstandardized β -13.699, p=0.014). Conclusion Chemerin increased progressively with the rise in albuminuria, and was associated with the inflammatory milieu in patients with DKD, given the significant association with the inflammatory markers TNF-α and ESR. TNF-α, as surrogate of inflammation, was strongly associated with albuminuria. As such, our results suggest a potential role of Chemerin and TNF-α in the development and progressions of DKD. Larger studies are warranted to further explore the potential links between chemerin, inflammation and DKD.


Author(s):  
Sudhir Kumar Ambati

Viral infections are common in people with type 2 diabetes, which is associated with poor immune responses. In type 2 diabetes, the normal functioning of the immune system and immune cells is suppressed, which allows the viruses to enter the host cells and cause infections. The impacts of type 2 diabetes on immune response and viral infections are associated with different mechanisms, including suppression or impairment of cytokine production, dysfunctioning of immune cells, defects in the phagocytosis, and disruption of natural killer cells. The high concentration of blood glucose or hyperglycemia in type 2 diabetes affects the production of cytokines, including interleukins, interferon, TNF-α, and IFN-γ. These cytokines are involved in fighting pathogens, and they induce the production of antibodies involved in the adaptive immune response. Therefore, disruption of these cytokines production leads to compromised immune response and invading pathogens like viruses enter and replicate in the host body. 


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