Neuroinflammation, diabetes, and COVID-19: Perspectives coming from Ca2+/cAMP signalling

2021 ◽  
Vol 14 ◽  
Author(s):  
Leandro Bueno Bergantin

Background: A link between inflammatory diseases, e.g., epilepsy, dementia, diabetes, and COVID-19, has been established. For instance, observational studies with several individuals established that people with epilepsy have shown an enhanced incidence of manifesting dysfunctions related to cognition, e.g., dementia, while people with dementia have a higher incidence of manifesting epilepsy, thus an evident bidirectional relationship between epilepsy and dementia might occur. In addition, epilepsy commonly cooccurs in patients with diabetes, so an association between these two disorders is also discussed. Intriguingly, some reports have also observed a poor prognosis for people with both diabetes and COVID-19. It is recognized that a dyshomeostasis of both Ca2+ and cAMP signalling pathways could be a molecular connection for these disorders. Objectives: Therefore, clarifying this clinical relationship among epilepsy, dementia, diabetes, and COVID-19 may outcome in novel hypotheses for identifying the etiology of these disorders.

2021 ◽  
Vol 6 (2) ◽  
pp. 43-56
Author(s):  
Gowhar Nazir ◽  
◽  
Josee Amin ◽  

Diabetes mellitus and periodontits are both highly prevalent chronic inflammatory diseases. Both diseases share the same risk factors and are a significant global health care burden adversely affecting the quality of life. Evidence from various studies have demonstrated that diabetes is a major risk factor for periodontal disease and is associated with increased incidence, prevalence and severity of periodontal disease. Hyperglycemia associated with diabetes mellitus results in an increased host immunoinflammatory response which adversely affects the periodontal health. Conversely, periodontits is associated with poor metabolic control in patients with diabetes and increased development of diabetic complications suggesting a bidirectional relationship between the two diseases. Periodontal infection via bacteremia exerts a wide systemic effect by contributing to chronic systemic inflammatory burden worsening diabetic state by increasing insulin resistance. Moreover, studies have demonstrated an improvement in glycemic control following periodontal therapy in prediabetic and diabetic patients with periodontitis.


2019 ◽  
Vol 22 (1) ◽  
pp. 35-43
Author(s):  
Elena E. Maslak ◽  
Victoria N. Naumova

Background: DM mellitus (DM) leads to worsening periodontal diseases, and in turn the inflammatory diseases of maxillofacial region adversely affect the glycemic control and exacerbate the severity of DM, thereby engendering a vicious cycle that compromises the DM management in patients. Taking account of the bidirectional relationship between DM and periodontal disease, interdisciplinary examination of patients with both DM and periodontal diseases is warranted to improve the health outcomes in patients. Aims: This study aims to evaluate the perceptions of dentists and endocrinologists on the interdisciplinary cooperation for identification and management of patients with DM. Materials and methods: Studying patients knowledge about DM and their compliance in providing endocrinological recommendations, dental screening survey to identify DM risk and signs The research was done in 2015-2016 years using clinical survey (dental status survey), statistical analysis. 432 patients from different dental organizations and 433 doctors (371 dentists and 62 endocrinologists) took part in the research. The research was approved by Regional research ethics committee. The written informed consent was taken from each participant. Results: There was insufficient interdisciplinary collaboration for identification and management of patients with diabetes, and lack of motivation among dental patients to endocrinological survey. Hence, it is important to incorporate definitive screening for risk of DM for patients with inflammatory periodontal disease and include dentists in consultation for patients with DM. The feasibility of statutory determination of collaboration between specialists in identification and management of patients with DM was found, dental lectures are necessary in DM school. Conclusions: Our findings suggest the necessity of including dentists in the standard of medical management of patients with DM and incorporating DM screening by a questionnaire upon dental examination.


2021 ◽  
pp. bjophthalmol-2020-318330
Author(s):  
Rohan Verma ◽  
Dongseok Choi ◽  
Allison J Chen ◽  
Christina A Harrington ◽  
David J Wilson ◽  
...  

BackgroundOrbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy.AimsTo test the hypothesis that shared signalling pathways are activated in different forms of OID.MethodsIn this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls.ResultsAmong the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways.ConclusionsAlthough OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Satoshi Ida ◽  
Ryutaro Kaneko ◽  
Kanako Imataka ◽  
Kazuya Murata

Previous studies involving patients with diabetes have indicated that sarcopenia is related to renal function. The objective of the present study was to investigate the association between sarcopenia and urinary albumin level, urinary protein level, and estimated glomerular filtration rate (eGFR) in patients with diabetes. A meta-analysis of observational studies was conducted. A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. Data were extracted from studies investigating the association between sarcopenia and urinary albumin level, urinary protein level, and eGFR and by calculating odds ratio (OR) and 95% confidence intervals (CIs). Statistical analysis was performed using a random-effects model to calculate pooled OR and 95% CI. Six studies (2662 patients) that met the criteria were included in the meta-analysis. Sarcopenia was significantly associated with urinary albumin level with a pooled OR of 2.11 (95% CI, 1.55–2.88; P<0.001). The pooled ORs of the associations between sarcopenia and urinary protein level and decreased eGFR were 1.82 (95% CI, 1.13–2.92; P=0.01) and 3.75 (95% CI, 1.24–11.41), respectively. Sarcopenia was significantly associated with urinary albumin level, urinary protein level, and decreased eGFR. However, further investigations are needed, including meta-analyses with a larger number of studies.


2020 ◽  
Vol 32 (1) ◽  
pp. 138-150 ◽  
Author(s):  
Simona Hapca ◽  
Moneeza K. Siddiqui ◽  
Ryan S.Y. Kwan ◽  
Michelle Lim ◽  
Shona Matthew ◽  
...  

BackgroundThere are few observational studies evaluating the risk of AKI in people with type 2 diabetes, and even fewer simultaneously investigating AKI and CKD in this population. This limits understanding of the interplay between AKI and CKD in people with type 2 diabetes compared with the nondiabetic population.MethodsIn this retrospective, cohort study of participants with or without type 2 diabetes, we used electronic healthcare records to evaluate rates of AKI and various statistical methods to determine their relationship to CKD status and further renal function decline.ResultsWe followed the cohort of 16,700 participants (9417 with type 2 diabetes and 7283 controls without diabetes) for a median of 8.2 years. Those with diabetes were more likely than controls to develop AKI (48.6% versus 17.2%, respectively) and have preexisting CKD or CKD that developed during follow-up (46.3% versus 17.2%, respectively). In the absence of CKD, the AKI rate among people with diabetes was nearly five times that of controls (121.5 versus 24.6 per 1000 person-years). Among participants with CKD, AKI rate in people with diabetes was more than twice that of controls (384.8 versus 180.0 per 1000 person-years after CKD diagnostic date, and 109.3 versus 47.4 per 1000 person-years before CKD onset in those developing CKD after recruitment). Decline in eGFR slope before AKI episodes was steeper in people with diabetes versus controls. After AKI episodes, decline in eGFR slope became steeper in people without diabetes, but not among those with diabetes and preexisting CKD.ConclusionsPatients with diabetes have significantly higher rates of AKI compared with patients without diabetes, and this remains true for individuals with preexisting CKD.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bo Cao ◽  
Xingcan Yao ◽  
Lifang Zhang ◽  
Xiaobo Hu ◽  
Min Chen ◽  
...  

Background. This meta-analysis was performed to compare the efficacy and safety of direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) for stroke prevention in real-world patients with diabetes and nonvalvular atrial fibrillation (NVAF) through observational studies. Methods. PubMed, Embase, and Web of Science databases were searched up to August 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) by using a random-effect model. Results. Seven observational studies involving 249,794 diabetic NVAF patients were selected. Compared with VKAs, the use of DOACs was associated with significantly reduced risks of stroke ( RR = 0.56 , 95% CI 0.45-0.70; p < 0.00001 ), ischemic stroke ( RR = 0.61 , 95% CI 0.48-0.78; p < 0.0001 ), stroke or systemic embolism (SSE) ( RR = 0.81 , 95% CI 0.68-0.95; p = 0.01 ), myocardial infarction ( RR = 0.69 , 95% CI 0.55-0.88; p = 0.002 ), major bleeding ( RR = 0.75 , 95% CI 0.63-0.90; p = 0.002 ), intracranial hemorrhage ( RR = 0.50 , 95% CI 0.44-0.56; p < 0.00001 ), and major gastrointestinal bleeding ( RR = 0.77 , 95% CI 0.62-0.95; p = 0.02 ), and a borderline significant decrease in major adverse cardiac events ( RR = 0.87 , 95% CI 0.75-1.00; p = 0.05 ) in NVAF patients with diabetes. Conclusion. For patients with NVAF and diabetes in real-world clinical settings, DOACs showed superior efficacy and safety profile over VKAs and significantly reduced risks of stroke, ischemic stroke, SSE, myocardial infarction, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding.


2020 ◽  
Author(s):  
Debmalya Barh ◽  
Sandeep Tiwari ◽  
Bruno Silva Andrade ◽  
Marianna E. Weener ◽  
Aristóteles Góes-Neto ◽  
...  

ABSTRACTTill date the comprehensive clinical pictures, comorbid conditions, and long-term complications of COVID-19 are not known. Recently using a multi-omics-based strategy, we have predicted the drugs for COVID-19 management with ∼70% accuracy. Here, using a similar multi-omics-based bioinformatics approach and three-ways of analysis, we identified the symptoms, comorbid conditions, and short, mid and possible long-term complications of COVID-19 with ∼90% precision. In our analysis (i) we identified 27 parent, 170 child, and 403 specific conditions associated with COVID-19. (ii) Among the specific conditions, 36 are viral and 53 short-term, 62 short to mid to long-term, 194 mid to long-term, and 57 are congenital conditions. (iii) At a cut off “count of occurrence” of 4, we found ∼ 90% of the enriched conditions are associated with COVID-19. (iv) Except the dry cough and loss of taste, all other COVID-19 associated mild and severe symptoms are enriched. (v) Cardiovascular, pulmonary, metabolic, musculoskeletal, neuropsychiatric, kidney, liver, and immune system disorders are found as top comorbid conditions. (vi) Specific diseases such as myocardial infarction, hypertension, COPD, lung injury, diabetes, cirrhosis, mood disorders, dementia, macular degeneration, chronic kidney disease, lupus, arthritis etc. along with several other diseases are also enriched as top candidates. (vii) Interestingly, many cancers and congenital disorders associated with COVID-19 severity are also identified. (viii) Arthritis, dermatomyositis, glioma, diabetes, psychiatric disorder, cardiovascular diseases having bidirectional relationship with COVID-19 are also found as top ranked conditions. Based on the accuracy (∼90%) of this analysis, long presence of SARS-CoV-2 RNA in human, and our previously proposed “genetic remittance” assumption, we hypothesize that all the identified comorbid conditions including the short-long-mid and mid-long non-communicable diseases (NCDs) could also be long-term consequences in COVID-19 survivors and warrants long-term observational studies.


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