ArticleLiterature Review

The Effect of Short-Term Hyperglycemia on the Innate Immune System

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Abstract

Background: Diabetes mellitus increases the susceptibility to infection by altering both the innate and the adaptive immune systems. Hyperglycemia has been associated with adverse outcomes in hospitalized patients, especially critically ill patients; these poor outcomes are explained in part by hospital-associated infections. Materials and methods: PubMed, EMBASE and Google Scholar were searched to identify studies published between 1970 and 2014 reporting short-term effects of hyperglycemia on the innate immune system. MeSH database search terms included hyperglycemia, immune system, inflammation, inflammation mediators, neutrophils, endothelial dysfunction, complement system proteins and diabetes. Pertinent articles reported studies in healthy volunteers and diabetic patients, using in vitro laboratory experiments, and with animal models. Results: Hyperglycemia activates protein kinase C, and this inhibits neutrophil migration, phagocytosis, superoxide production and microbial killing. High glucose concentrations decrease the formation of neutrophil extracellular traps. Hyperglycemia can also induce Toll-like receptor expression and inhibit neutrophil function and apoptosis. High glucose concentrations decrease vascular dilation and increase permeability during the initial inflammatory responses, possibly through protein kinase C activation. Hyperglycemia can cause direct glycosylation of proteins and alter the tertiary structure of complement; these changes inhibit immunoglobulin-mediated opsonization of bacteria and complement fixation to bacteria and decreases phagocytosis. Hyperglycemia also stimulates the production and release of cytokines. Several trials have demonstrated that better glycemic control reduces nosocomial infections in critically ill patients and surgical site infections. Conclusions: In summary, acute hyperglycemia can significantly alter innate immune responses to infection, and this potentially explains some of the poor outcomes in hospitalized patients who develop hyperglycemia.

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... Innate immune system, the first line of defense against SARS-CoV-2, is compromised in patients with DM which is known to impair the process of chemotaxis and phagocytosis in polymorphonuclear neutrophils )PMNs(. 9 Diabetes mellitus has been shown to be a pro-inflammatory condition due to the excess production of the cytokines. Coronavirus disease-19 patients, with pre-existing DM, have shown to have higher serum interleukin-6 )IL-6(, C-reactive protein )CRP(, and ferritin levels than those without DM. ...
... p=0.041( than non-diabetic patients. They also had longer duration of hospital stay )median [IQR]: 13 [10] vs. 11 [9]; p=0.027( than non-diabetic patients. Table 3 highlights various laboratory parameters among both the groups. ...
... 25 Previous studies and meta-analyses have shown that hypertension, DM, IHD, CKD, COPD, and active malignancies all were associated with higher mortality in COVID-19 patients. [7][8][9][10]33,34 Similarly, in our study, age, hypertension, DM, and IHD were significantly associated with higher mortality; however, only age was an independent risk factor on multivariate analysis as mortality increased with increasing age )p=0.006(. This difference can be explained by the small sample size to prove such association. ...
Article
Objectives: To describe the effect of diabetes mellitus (DM) on clinical outcomes of patients admitted with COVID-19 infection. Methods: We carried out a single center, observational, retrospective study. We included adult patients with laboratory-confirmed diagnosis of COVID-19 admitted to a tertiary hospital in Jeddah, Saudi Arabia, from April 2020 to December 2020. Electronic medical records were reviewed for demographics, clinical status, hospital course, and outcome; and they were compared between the patients with or without DM. Results: Out of 198 patients included in the study, 86 (43.4%) were diabetic and 112 (56.5%) were non-diabetic. Majority of the patients were males 139 (70.2%) with a mean age of 54.14±14.89 years. In-hospital mortality rate was higher in diabetic patients than in non-diabetic patients (40 vs. 32; p=0.011). The most common comorbidity was hypertension (n=95, 48%) followed by ischemic heart disease (n=35, 17.7%), chronic kidney disease (n=17, 9.6%), and bronchial asthma (n=10, 5.1%). Conclusion: The risk of SARS-CoV-2 infection is higher among diabetic patients; particularly, those with preexisting co-morbidities or geriatric patients. Diabetic patients are prone to a severe clinical course of COVID-19 and a significantly higher mortality rate.
... 4 It was seen that the prevalence of diabetes mellitus was two to threefold higher in patients admitted to intensive care units (ICUs) and the mortality rate was almost double that of the non-diabetic patients. 5 Hyperglycemia in diabetes mellitus interferes with host-viral interactions and host-immune responses through several mechanisms leading to poorer outcomes. 4,5 Furthermore, some studies have reported that COVID-19 has been implicated in the development of new-onset diabetes mellitus. ...
... 5 Hyperglycemia in diabetes mellitus interferes with host-viral interactions and host-immune responses through several mechanisms leading to poorer outcomes. 4,5 Furthermore, some studies have reported that COVID-19 has been implicated in the development of new-onset diabetes mellitus. 5 There is a paucity of data regarding the effect of diabetes mellitus and associated comorbidities on the clinical presentation and outcome of symptomatic patients with COVID-19 in comparison with the non-diabetic patients. ...
... 4,5 Furthermore, some studies have reported that COVID-19 has been implicated in the development of new-onset diabetes mellitus. 5 There is a paucity of data regarding the effect of diabetes mellitus and associated comorbidities on the clinical presentation and outcome of symptomatic patients with COVID-19 in comparison with the non-diabetic patients. Thus, the main purpose of this study was to measure, compare, and describe the clinical and biochemical parameters of COVID-19 patients admitted to ICU, with and without diabetes mellitus. ...
Article
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Background: Elderly population, individuals with metabolic derangements such as diabetes mellitus and obesity, and immunocompromised patients are falling prey to the severity of illness caused by the SARS-CoV-2 viral infection. India, deemed as the “Diabetes Capital of the World,” has a large population vulnerable to COVID-19 infection and its complications. Aims and Objectives: This study was conducted to measure, compare, and describe the clinical and biochemical parameters of COVID-19 patients admitted to the intensive care unit, with and without diabetes mellitus, and their outcomes in terms of morbidity and mortality. Materials and Methods: A cross-sectional comparative study was conducted on 146 hospitalized patients with COVID-19 disease confirmed with reverse transcription polymerase chain reaction, 66 of them categorized as diabetic and 80 as non-diabetic. Details of socio-demographic variables, medical history, and comorbidities of the patients were collected using a pre-tested and validated questionnaire. Vital signs and hematological, biochemical, and respiratory parameters were recorded and analyzed among both the groups of COVID-19 patients. Results: There were statistically significant differences in the age, sequential organ failure assessment scores at admission, SpO2, HbA1c, blood urea, creatinine, serum potassium, random blood sugar, ALT, pCO2, PaO2, acute respiratory distress syndrome (PaO2/FiO2), and the length of hospital stay between the diabetic and non-diabetic patients. Conclusion: Hospitalized patients with COVID-19 disease with diabetes mellitus have higher levels of inflammatory markers and of other predictors of severity of illness, need for admission in critical care units, and risk of in-hospital deaths compared to non-diabetic patients.
... Both hypoglycemia and direct viral interaction with the heme group of hemoglobin (the decrease of this parameter was observed during this study, see Table 2) lead to an increase in heme serum levels in COVID-19 patients. With harmful iron ions, both hypoglycemia and heme induces an inflammatory process (Liu and Li, 2022;Jafar et al., 2016). This inflammation results in high CRP and LDH concentrations as observed in our study. ...
... Elevated cytokine levels linked to COVID-19 severity lead to an increase of activated neutrophils that recognize the virus and coordinate its elimination with adaptive immune responses. However, in some cases like hyperglycemia, they contribute to severe forms of COVID-19 and fatal outcomes by disseminating the virus which leads to both inflammation and tissue damage (Jafar et al., 2016;Rodrigues et al., 2020). Indeed, neutrophils intensively infiltrate the lung and induce an inflammatory process (Parthasarathi et al., 2022). ...
Article
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The COVID-19 disease presents a large range of clinical manifestations and includes asymptomatic, mild, and severe cases. The level of severity is related to parameters associated with immunity, genetics, and biochemistry. Africa shows one of the lowest COVID-19 fatality rates but very few data on the biochemical markers of COVID-19 in patients and the factors associated with disease severity are available for the continent. In Gabon, the COVID-19 fatality rate is only 0.63% but almost no data on biomarkers in COVID-19 patients have been published. Both the number of COVID-19 cases and the mortality rate reported in Africa in general, and in Gabon in particular, are lower than in non-African countries. As such, understanding the factors associated with disease severity in Gabonese patients is a crucial step to better understand the disease in the African context and prepare for future COVID-19 waves and other epidemics of emerging diseases. Here, we compared biochemical and hematological markers among 753 Gabonese COVID-19 patients with asymptomatic (184/753), mild/moderate (420/753), and severe/critical (149/753) forms of the disease using an Analysis of Variance (ANOVA) or a Kruskal-Wallis (KW) test. We modeled these parameters together with comorbidities, age, and sex to predict factors associated with disease severity by using a "binomial generalized linear model" utilizing the "package" stats of R software version 4.0.2. Our results showed that almost all the biochemical and hematological parameters (except creatinine, phosphorus, D-dimers, platelets, and monocytes) varied according to disease severity. However, age and the dysfunction of organs like the kidney, liver, and lung together with the decrease of electrolytes (chloride, potassium, and sodium) are the best predictors of disease severity in Gabonese patients.
... Epidemiological data show that individuals with T2DM have a higher risk of developing infections or tumors [4][5][6][7][8]. Additionally, some data suggest that the immune system in T2DM patients is impaired, highlighting the need to study the relationship between immunity and glucose metabolism [9][10]. ...
... Autoimmune responses might lead to pancreatic in ammation, disrupting the insulin system [21][22][23][24][25][26]. Hyperglycaemia not only affects the heart, vasculature, and kidneys but also conversely damages the immune system, leading to serious diseases, including an increased risk of infection and tumor [4][5][6][7][8][9][10]. Therefore, further understanding of the association between blood glucose levels and immune dysfunction in T2DM might help to control these diseases. ...
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Background To explore the M-MDSCs frequency in T2DM patients and whether it is corelated to the glycaemia, infection and tumor development. Methods We recruited healthy volunteers and T2DM patients for this study. M-MDSCs frequency in the peripheral blood, FPG, HbA1c levels, and other relevant indicators were detected. T2DM patients were further divided into good glycaemic control (GGC) and poor control (PGC) groups, and each patient was followed up for at least 6 months after the M-MDSCs were tested. We then analysed and compared the M-MDSCs frequency in the healthy population to various subgroups of T2DM patients, as well as the associations between M-MDSCs, glycaemia, infection, and tumor development. Results The M-MDSCs frequency was significantly higher in T2DM patients with PGC than in the healthy population (2.54% vs 0.93%), but there was no significant difference between patients with GGC and the healthy group (P > 0.05). The M-MDSCs frequency was positively correlated with FPG and HbA1c levels (R = 0.517 and 0.315, respectively). In addition, the patients who had tumors had the highest M-MDSCs number (12.89%), vastly more than those in the patients who only had an infection (3.14%) and the patients who had neither infection nor tumor (1.95%). When M-MDSCs frequency was higher than 2.8% or 11.24%, the risk ratios for infection or tumor occurrence were 2.5-fold and 43.2-fold higher in T2DM patients, respectively. Conclusions Elevated M-MDSC levels are associated with hyperglycaemia and may be a useful indicator for predicting the risk of infection or tumor development in T2DM patients.
... Various studies have reported that excessive inflammation was reported to be responsible for both morbidity and mortality in COVID-19 patients. [113][114][115][116] A postmortem study of patients who died of COVID-19 found that most of them had high levels of circulating cytokines, profound lymphopenia and substantial mononuclear cell infiltration, which are responsible for inflammation, in organs such as the lungs, heart and kidneys. 117,118 One study found that hyperglycaemia contributed to chronic inflammation by mediating the formation of advanced glycosylation endproducts, which in turn elevated inflammatory indices. ...
... One of the key problems associated with COVID-19 is the cytokine storm. The Table 2 Studies on the influence of diabetes mellitus on the immune system Study Morey et al. 94 Jafar et al. 113 Graves and Kayal. 98 Esposito et al. 114 System TNF-alpha Increased ND Increased Increased Increased Neutrophil counts ND Decreased ND ND ND Interleukin-6 Increased ND ND Increased Increased Chemokines Increased ND ND ND ND cytokine storm is characterised by a drastic increase in immune cell production of inflammatory cytokines, which mediates tissue inflammation resulting to organ damage. ...
Article
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Beginning in December 2019 and still ongoing, coronavirus disease 2019 (COVID-19) infections have posed a public health challenge worldwide. There have been reports of diabetes mellitus (DM) as one of the most prevalent comorbidities in patients with COVID-19. Although the interactions and possible mechanisms of this association have not been fully established, the existence of DM is believed to aggravate the adverse effects of COVID-19 infection. Hence, the need for this paper. Findings from other studies have shown different possible mechanisms of how COVID-19 and DM aggravate the severity of each other. Among the hypothetical mechanisms reported between COVID-19 and DM in this paper are: COVID-19 causes complications of DM through the following: (1) Destruction of β-cells in the pancreas by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. (2) Cytokine storm generation which mediates tissue inflammation resulting in organ damage and (3) The use of corticosteroid drugs which have been found to be highly diabetogenic. Similarly, DM facilitates internalizing of SARS-CoV-2 symptoms through increasing expression of angiotensin-converting enzyme 2 (ACE2) and the furin protein, viral load, entrance and replication of SARS-CoV-2, glycosylation, and compromising of the immune response that worsens COVID-19. Having a clear understanding of the biochemical mechanisms of interactions between COVID-19 and DM may be useful for future research of agents targeted as therapeutic remedies for managing patients with diabetes infected with COVID-19 and vice versa.
... A rapid increase in blood glucose concentration (BGC) after graft reperfusion is one of them [1,2]. Intraoperative hyperglycemia is associated with decreased immunity, increased ischemia-reperfusion injury, infectious complications, and mortality [3][4][5][6][7][8][9][10]. Accordingly, liver transplant anesthesiologists give efforts to maintain glycemic homeostasis after graft reperfusion [9]. ...
... This is important because hyperglycemia even during a short period is known to affect clinical courses. First, acute transient hyperglycemia even during a short period disturbs the innate immune system by inhibiting neutrophil migration, phagocytosis, and complement function, and by stimulating inflammatory cytokines and decreasing microvascular reactivity [3,4]. Deterioration of innate immune response can promote infection progress [6,7,9]. ...
Article
Background: The Portland intensive insulin therapy effectively controls acute hyperglycemic change after graft reperfusion during liver transplantation. However, the time-consuming sophistication acts as a barrier leading to misinterpretation and decreasing compliance to the protocol; thus, we newly introduced an application software "Insulin protocol calculator" which automatically calculates therapeutic bolus/continuous insulin doses based on the Portland protocol. Methods: Of 144 patients who underwent liver transplantation, 74 patients were treated before the introduction of "Insulin protocol calculator" by using a paper manual, and 70 patients were treated by using the application. Compliance was defined as the proportion of patients treated with exact bolus/continuous insulin dose according to the Portland protocol. Results: Compliance was significantly greater in app group than in paper group regarding bolus dose (94.5% and 86.9%, P < 0.001), continuous dose (88.9% and 77.3%, P = 0.001), and both doses (86.6% and 73.8%, P < 0.001). Blood glucose concentration was significantly lower in app group at 3 h (125 ± 17 mg/dl vs. 136 ± 19 mg/dl, P = 0.014) and 4 h (135 ± 22 mg/dl vs. 115 ± 15 mg/dl, P = 0.029) after graft reperfusion. Acute hyperglycemic change during 30 min was more prominent in app group while hyperglycemia incidence was 71.4% vs. 54.1% (P = 0.031). However, hyperglycemia risk was comparable at 2 h (31.4% vs. 31.1%, P = 0.964), and even insignificantly lower in app group at 3 h (7.1% vs. 19.5%, P = 0.184). Conclusions: Compliance to the Portland protocol was significantly improved after introducing the application software; post-reperfusion hyperglycemia was better controlled. "Insulin protocol calculator" is cost-effective and time-saving with potential clinical benefits.
... Together, these reports suggest that diabetic conditions, particularly high glucose, lead to enhanced NETosis. However, other reports indicate that high glucose concentrations decrease the formation of NETs [182,183]. ...
... Neutrophils of diabetic individuals display lower phagocytic activity [159], lower production of ROS [225], and lower chemotactic capacity [238] than neutrophils from healthy control individuals. Some of these functions (migration and bacteria killing) also seem to be compromised in hyperglycemia, and can be induced in vitro upon exposure of neutrophils to serum from diabetic patients [182]. Finally, recent experiments showed that neutrophils can release microvesicles, which are involved in cell-cell communication. ...
Article
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Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state by producing cytokines and chemokines that can reach other parts of the body, creating a systemic inflammatory condition. In this review, we described the recent findings on the role of neutrophils during obesity and the initiation of inflammation. In addition, we discuss the involvement of neutrophils in the generation of obesity-related complications using diabetes as a prime example.
... T2DM and uncontrolled hyperglycemia alters both the humoral as well as the innate immunity (i.e., the cell mediated), [70] resulting in diminished first line of defense against any pathogens. A pro-inflammatory stage is caused by T2DM with a hyperbolic cytokine response. ...
Article
Introduction: In uncontrolled hyperglycemia, lungs, tongue, oropharyngeal and nasopharyngeal airways having increased glycosylated angiotensin-converting enzyme 2 (ACE2) can serve as good viral binding sites for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to a greater tendency and considerable risk of prolonged life-threatening disease. This review was written with the objective to extract the recent advances, updates, and discoveries about the effects of coronavirus disease-2019 (COVID-19) on patients with diabetes and its microvascular complications. It was further written with the aim to discuss the current state of knowledge that has not yet been confirmed or unconfirmed, leading to various debatable issues about COVID-19-associated with microvascular complications in diabetes mellitus. Materials and Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched scientific sites related to our review article such as Web of Science, Embase, PubMed, Scopus, Google Scholar, and MEDLINE of last nearly two and half years. Results: The individuals who are suffering from type 2 diabetes mellitus experience more organ damage by SARS-Cov-2 due to cytokine storm. The pro-inflammatory state, lower primary immune system response, and increased ACE2 level with dysregulation of vascular function and the prothrombic state in patients with diabetes may increase the vulnerability for COVID-19 and worsened prognosis. The patients have reduced prognosis leading to microvascular complications such as diabetic nephropathy, neuropathy and retinopathy. In diabetes retinopathy, it induces the changes in the vasculature of the retinal veins. These viruses can directly affect the nervous tissue and/or can indirectly via activating the immune system-mediated mechanisms leading to diabetic neuropathy as well. Conclusions and Implications: During the cytokine storm the amount of D-dimer in the serum gets significantly increased, due to increased activating plasmin at the early stage of inflammation. Uncontrolled hyperglycemia leads to diabetic complications leading to increased mortality rate in patients with COVID-19. Thus, diabetes and its associated microvascular complications may lead to the severity and mortality in the patients with COVID-19. More of clinical practice and further studies should be implicated through this review article. Laboratory findings and clinical records are of much help in patients with diabetes and COVID-19. Worldwide studies from different countries apart from China should be considered to reach a conclusion about the conditions of patients with diabetes and microvasculature complications around the world.
... When healthy individuals' blood was exposed to bacterial wall components after becoming hyperglycemic the blood's neutrophil degranulation reduces. Another example of neutrophil dysfunction in S. aureus phages was provided by C3-mediated complement suppression brought on by hyperglycemia [36]. It is reported that NETs, which increase susceptibility to infections, are less likely to form when hyperglycemia is present. ...
Chapter
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Diabetes is an age-dependent health issue prevalent worldwide and specially seen in those families with prevalent history of the disorder. Insufficient insulin production by the defective pancreas that leads to high blood glucose levels in the systemic circulation makes the patients more prone to an infection that exaggerates with time as compared to their counterparts. This increased prevalence of infections in diabetics may be due to defects in the immune functionality of the diabetes patients. High blood glucose level evokes inflammatory responses due to provoked inflammatory immune response against hyperglycemic condition in adipocytes and macrophages. The inflammatory mediators attack the pancreatic beta cells thus affecting the insulin production, which in-turn again results in hyperglycemia. Dysfunction of the immune response could not control the invasion of pathogens thereby, increasing the incidence of infectious diseases and related co- morbidities. This chapter discusses about immune dysfunction and suppression in T2DM and the underlying inflammation and infections in diabetics. An elaborate and in-depth understanding of the immune dysfunction in T2DM patients can help in the management and development of better targeted therapeutics to cure the disorder. It may also provide an insight in how to take care of one’s health as a precautionary measure to avoid the complications leading to diabetes and vice versa.
... In a single case study, neutrophils from a GSD-Ib patient had decreased phagocytosis and killing capacity to S. aureus, E. coli and P. gengivalis [44]. Diabetes mellitus, a clinical syndrome associated with the deficiency of insulin secretion or action, is among the known diseases that undermine host defences and increases the susceptibility to bacterial infections mainly through modulation of the immune system [45]. The hyperglycaemic environment blocks G6PD, increasing neutrophil apoptosis and chemotaxis. ...
Article
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Neutrophils are front line cells in immunity that quickly recognize and eliminate pathogens, relying mainly on glycolysis to exert their killing functions. Even though investigations into the influence of metabolic pathways in neutrophil function started in the 1930s, the knowledge of how neutrophils metabolically adapt during a bacterial infection remains poorly understood. In this review, we discuss the current knowledge about the metabolic regulation underlying neutrophils response to bacterial infection. Glycogen metabolism has been shown to be important for multiple neutrophil functions. The potential contribution of metabolic pathways other than glycolysis, such as mitochondrial metabolism, for neutrophil function has recently been explored, including fatty acid oxidation in neutrophil differentiation. Complex III in the mitochondria might also control glycolysis via glycerol-3-phosphate oxidation. Future studies should yield new insights into the role of metabolic change in the anti-bacterial response in neutrophils.
... Bu durum da diyabetli bireyleri COVID-19'a yakalanma bakımından daha duyarlı hale getirebilmektedir. Diyabet hem doğuştan gelen hem de adaptif immün sistemleri değiştirerek enfeksiyon hastalıklarına yatkınlığı artırmaktadır (13). Diyabetli bireylerde T hücre fonksiyonunun, viral klirensin ve fagositik aktivitenin azalması gibi diyabetin immün sistem üzerindeki potansiyel olumsuz etkilerinin COVID-19'a yatkınlığı artırabileceği belirtilmektedir (14). ...
Chapter
Giriş Diyabet metabolik ve kardiyovasküler komplikasyonlar ile seyreden kronik inflamatuvar bir hastalıktır. Diyabet toplumda yaygın görülen bir halk sağlığı sorunu olup hem küresel hem ulusal düzeyde 2000 yılından bu yana artan bir seyir göstermiştir. Uluslararası Diyabet Federasyonu 2021 raporuna göre küresel düzeyde diyabet prevalansının 9,8 olduğu (537 milyon kişi) ve 2045 yılında prevalansın 11,2’ye artacağı (783 milyon kişi) tahmin edilmektedir. Ülkemizde ise yaklaşık 9 milyon (%14,5) diyabetli olduğu belirtilmektedir (1). Aynı rapora göre diyabet, son dönem böbrek yetmezliği, erişkin başlangıçlı körlük ve alt ekstremite ampütasyonları gibi komplikasyonlara sebep olmaktadır. Diyabetik komplikasyonlar da yeti yitimine ve yaşamı tehdit eden bozukluklara neden olmaktadır (2). COVID-19, Çin’in Wuhan kentinde 2019 yılının Aralık ayında yeni bir enfeksiyon hastalığı olarak ortaya çıkmış ve kıtalar arasında hızla yayılmıştır ve şiddetli akut solunum yolu sendromu olarak tanımlanmıştır (3). COVID-19’un etkeni SARS-CoV-2 olarak isimlendirilen tek zincirli, pozitif polariteli, zarflı bir RNA virüsüdür (4). COVID-19, insandan insana damlacık yoluyla bulaşmaktadır. Enfeksiyon etkeni hasta bir kişi öksürdüğünde, hapşırdığında veya konuştuğunda solunum salgılarında bulunan virüs, mukozayla doğrudan temas ederse başka bir kişiye bulaşabilir. Ayrıca enfenksiyon etkenine sahip bir bireyin öksürme, hapşırma yoluyla ortaya saçtıkları damlacıkların sağlıklı kişinin elleri ile temas etmesi sonrasında ağız, burun veya göz mukozasına götürmesi ile de bulaşmaktadır. (4). Kesin olarak inkübasyon süresi bilinmemektedir ancak virüs etkenine maruziyet sonrası 2 ila 14 gün arası olduğu ve çoğu vakanın etkenle temastan 5 gün içerisinde ortaya çıktığı düşünülmektedir (5). COVID-19 enfeksiyonu, tüm yaş gruplarının özellikle de kronik hastalığı bulunan bireylerin sağlığını daha olumsuz etkilemektedir (6). Özellikle diyabetli bireylerin COVID-19’a yakalanma bakımından daha duyarlı hale geldiği ve COVID-19 tanısı aldıklarında COVID-19’un şiddetli seyir gösterme potansiyelinin yüksek olduğu belirtilmektedir (6-9).
... Chronic hyperglycemia continuously stimulates polymorphonuclear lymphocytes and baseline cytokine levels, causing cellular and humoral responses insufficient for pathogens (Dryden et al., 2015). Hyperglycemia impairs neutrophils, significantly reducing their chemotactic migration, phagocytosis, and bactericidal functions (Jafar et al., 2016). Poor glycemic control in DM2 patients also suppresses the immune activity of monocytes and monocyte-derived macrophages (MDM) (Valtierra-Alvarado et al., 2020). ...
Article
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Diabetes mellitus (DM) is a group of metabolic diseases marked by hyperglycemia, which increases the risk of systemic infections. DM patients are at greater risk of hospitalization and mortality from bacterial, viral, and fungal infections. Poor glycemic control can result in skin, blood, bone, urinary, gastrointestinal, and respiratory tract infections and recurrent infections. Therefore, the evidence that infections play a critical role in DM progression and the hazard ratio for a person with DM dying from any infection is higher. Early diagnosis and better glycemic control can help prevent infections and improve treatment outcomes. Perhaps, half (49.7%) of the people living with DM are undiagnosed, resulting in a higher frequency of infections induced by the hyperglycemic milieu that favors immune dysfunction. Novel diagnostic and therapeutic markers for glycemic control and infection prevention are desirable. High-throughput blood-based immunoassays that screen infections and hyperglycemia are required to guide timely interventions and efficiently monitor treatment responses. The present review aims to collect information on the most common infections associated with DM, their origin, pathogenesis, and the potential of immunoproteomics assays in the early diagnosis of the infections. While infections are common in DM, their role in glycemic control and disease pathogenesis is poorly described. Nevertheless, more research is required to identify novel diagnostic and prognostic markers to understand DM pathogenesis and management of infections. Precise monitoring of diabetic infections by immunoproteomics may provide novel insights into disease pathogenesis and healthy prognosis.
... Phagocytosis by monocytes, neutrophils, and macrophages was low in diabetic patients who also suffer from disruptions in neutrophil chemotaxis, anti-bacterial activity, and innate immune function [43]. Surprisingly, short-term hyperglycemia reduces innate immune function [44]. Next to their malfunction in innate immune response, diabetic patients also have a disturbed adaptive immune function [45]. ...
Article
Coronavirus disease 2019 (COVID-19), a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now at pandemic levels leading to considerable morbidity and mortality throughout the globe. Patients with obesity, diabetes, and metabolic syndrome (MetS) are mainly susceptible and more probably to get severe side effects when affected by this virus. The pathophysiologic mechanisms for these notions have not been completely known. The pro-inflammatory milieu observed in patients with metabolic disruption could lead to COVID-19-mediated host immune dysregulation, such as immune dysfunction, severe inflammation, microvascular dysfunction, and thrombosis. The present review expresses the current knowledge regarding the influence of obesity, diabetes mellitus, and MetS on COVID-19 infection and severity, and their pathophysiological mechanisms.
... Hyperglycemia significantly contributed to SAP occurrence in our cohort. This is evidenced by the results of several studies, which demonstrated that glucose level has satisfactory values for predicting SAP (16,39). Noteworthy, hyperglycemia reduces the neutrophil's bactericidal ability by inhibiting migration, phagocytosis, and superoxide production (40). ...
Article
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Background Stroke-associated pneumonia (SAP) commonly complicates acute ischemic stroke (AIS) and significantly worsens outcomes. Type 2 diabetes mellitus (T2DM) may contribute to malnutrition, impair innate immunity function, and increase the probability of SAP occurrence in AIS patients. We aimed to determine early predictors of SAP in AIS patients with T2DM and to construct a nomogram specifically for predicting SAP in this population by combining the A ² DS ² score with available nutrition-related parameters. Methods A total of 1,330 consecutive AIS patients with T2DM were retrospectively recruited. The patients were randomly allocated to the training ( n = 887) and validation groups ( n = 443). Univariate and multivariate binary logistic regression analyses were applied to determine the predictors of SAP in the training group. A nomogram was established according to the identified predictors. The areas under the receiver operating characteristic curve (AUROC) and calibration plots were performed to access the predictive values of the nomogram. The decision curve was applied to evaluate the net benefits of the nomogram. Results The incidence of SAP was 9% and 9.7% in the training and validation groups, respectively. The results revealed that the A ² DS ² score, stroke classification, Geriatric Nutritional Risk Index, hemoglobin, and fast blood glucose were independent predictors for SAP. A novel nomogram, A ² DS ² -Nutrition, was constructed based on these five predictors. The AUROC for A ² DS ² -Nutrition (0.820, 95% CI: 0.794–0.845) was higher than the A ² DS ² score (0.691, 95% CI: 0.660–0.722) in the training group. Similarly, it showed a better predictive performance than the A ² DS ² score [AUROC = 0.864 (95% CI: 0.828–0.894) vs. AUROC = 0.763 (95% CI: 0.720–0.801)] in the validation group. These results were well calibrated in the two groups. Moreover, the decision curve revealed that the A ² DS ² -Nutrition provided an additional net benefit to the AIS patients with T2DM compared to the A ² DS ² score in both groups. Conclusion The A ² DS ² score, stroke classification, Geriatric Nutritional Risk Index, hemoglobin, and fast blood glucose were independent predictors for SAP in AIS patients with T2DM. Thus, the proposed A ² DS ² -Nutrition may be a simple and reliable prediction model for SAP occurrence in AIS patients with T2DM.
... 9 Impaired glycemic control affects both the innate and the adaptive immune systems making the first line of defense less effective to counter infections. 10 In parallel, glucose lowering medications (GLM) may alter the response to coronavirus infection. Metformin, for example, seems to reduce mortality in COVID-19 patients, 11 while the evidence on DPP4i (Dipeptidyl-Peptidase-4 inhibitors) is conflicting 12,13 and insulin appears to be associated with higher mortality rates. ...
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Purpose: Diabetes is a risk factor for COVID-19 severity, but the role played by glucose lowering medications (GLM) is still unclear. The aim of this study was to assess infection rates and outcomes of COVID-19 (hospitalization and mortality) in adults with diabetes assisted by the Local Health Unit of Padua (North-East Italy) according to the ongoing GLM. Patients and methods: People with diabetes were identified using administrative claims, while those with SARS-CoV-2 infection were detected by cross referencing with the local COVID-19 surveillance registry. A multivariate logistic regression model was used to verify the association between GLM classes and the outcome. Results: SARS-CoV-2 infection rates were marginally but significantly higher in individuals with diabetes as compared to those without diabetes (RR 1.04, p = 0.043), though such relative 4% increase may be irrelevant from a clinical and epidemiological perspective. 1923 individuals with GLM-treated diabetes were diagnosed with COVID-19; 456 patients were hospitalized and 167 died. Those treated with insulin had a significantly higher risk of hospitalizations for COVID-19 (OR 1.48 p < 0.01) as were those treated with sulphonylureas/glinides (OR 1.34, p = 0.02). Insulin use was also significantly associated with higher mortality (OR 1.90, p < 0.01). Use of metformin was significantly associated with lower death rates (OR 0.62, p = 0.02). The association of other GLM classes with the outcome was not significant. Conclusion: Diabetes does not appear to modify the risk of SARS-CoV-2 infection in a clinically meaningful way, but strongly increases the rates of hospitalization and death. Insulin use was associated with worse outcomes, whereas metformin use was associated with lower mortality.
... According to research from China and Italy, people with diabetes who were infected with Covid-19 had higher hospital admission rates . As part of the pathophysiology of diabetes, especially in those with uncontrolled glycemia, the innate immune system and humoral immunity are compromised against any infection, including SARS-Cov-2 ineffectiveness (Jafar, N. et al., 2016). Additionally, diabetes results in an elevated cytokine response, which causes an inflammatory condition. ...
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Pandemic Covid-19 infection is an occurrence of a newly virus that discovered spreads quickly over the world, causing systemic or local pneumonia consequences, and was dubbed the virus in China. In 02/ 2020, this illness has been classified as Covid�19 by the WHO (Henry, B. M. et al., 2020). On 11/03/2020, the world health organization declared a SARS-CoV-2 contagion (Castle, S. 2020). In this review, a comparison between studies conducted in Iraq and other countries about some hematological, biochemical, and immunological studies of Covid-19. It was concluded that Covid-19 patients suffers from lymphopenia and neutrophilia and they were mostly with blood group A. There is an association between the severity of Covid-19 disease and serum levels of D-dimer and serum ferritin. There is relationship between the intensity of the disease and kidney problems. C-reactive protein levels increased with the severity of the disease. IL-6 levels linked with the severity of Covid-19. Here in the current review, summarizes some findings of some studies conducted in Iraq on the relationship of Covid-19 infections with some blood biomarkers including, hematological, biochemical and immunological parameters, and compare them with other studies conducted in different countries.
... Some of the possible explanations for this include: (a) compromised innate immunity, which is the first line of defense against COVID-19. Uncontrolled diabetes leads to reduced innate immunity, which gives rise to the unhindered proliferation of the virus [28,29]. (b) Exaggerated cytokine storm response: even in the absence of immune stimulation, diabetes is associated with a pro-inflammatory state characterized by increased levels of interleukin (IL)-1, IL-6, tumor-necrosis factor (TNF)-α, and ferritin. ...
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Background: COVID-19 has been associated with a higher risk of death in patients with diabetes mellitus (DM). However, there is a dearth of data regarding the effects of diabetic ketoacidosis (DKA) in these patients. We explored the in-hospital outcomes of patients who presented with COVID-19 and DKA. Methods: A propensity score-matched observational retrospective cohort study was conducted in hospitalized patients with COVID-19 in the public healthcare system of New York City from 1 March 2020 to 31 October 2020. Patients were matched, and a subgroup analysis of patients with DKA and COVID-19 and patients without COVID-19 was conducted. Results: 13,333 (16.0%) patients with COVID-19 and 70,005 (84.0%) without COVID-19 were included in the analysis. The in-hospital mortality rate was seven-fold in patients with DKA and COVID-19 compared to patients with COVID-19 and without DKA (80 (36.5%) vs. 11 (5.4%), p < 0.001). Patients with COVID-19 and DKA had a two-fold higher likelihood for in-hospital death (OR: 1.95; 95% CI: 1.41–2.70; p < 0.001) after adjusting for multiple variables. Conclusions: DKA was associated with significantly higher in-hospital mortality in hospitalized patients with COVID-19.
... We found significantly decreased phagocytic capacity within the macrophages of PTB + DM and DM patients plausibly due to diabetes-mediated intrinsic defect in these cells. Hyperglycemia can promote direct glycosylation of various proteins, including complements, and modify their tertiary structure, which can limit bacterial opsonization and thereby impair phagocytosis [15]. A subset of TB+DM patients with HbA1c levels of 7.5-8.0 ...
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Diabetes mellitus (DM) alters immune responses and given the rising prevalence of DM in tuberculosis (TB) endemic countries; hyperglycemia can be a potential risk factor for active TB development. However, the impact of hyperglycemia on TB specific innate immune response in terms of macrophage functions remains poorly addressed. We assessed macrophage effector functions in uncontrolled DM patients with or without TB infection (PTB+DM and DM), non‐diabetic TB patients (PTB) and non‐diabetic‐uninfected controls. Phagocytic capacity against BCG and surface expression of different pattern recognition receptors (PRRs) (CD11b, CD14, CD206, MARCO, and TLR‐2) were measured via flow cytometry. Effector molecules (ROS and NO) required for bacterial killing were assessed via DCFDA and Griess reaction respectively. A systematic dysregulation in phagocytic capacity with concurrent alterations in the expression pattern of key PRRs (CD11b, MARCO, and CD206) was observed in PTB+DM. These altered PRR expressions were associated with decreased phagocytic capacity of macrophages. Similarly, ROS was aberrantly higher while NO was lower in PTB+DM. These altered macrophage functions were positively correlated with increasing disease severity. Our results highlight several key patterns of immune dysregulation against TB infection under hyperglycemic conditions and highlight a negative impact of hyperglycemia with etiology and progression of TB. This article is protected by copyright. All rights reserved
... Long-term hyperglycemia is known to increase reactive oxygen release, lead to cellular damage and electrolyte imbalance, and impair immune functions [49]. However, there are publications in the literature showing that the presence of diabetes does not increase mortality [50,51]. ...
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Background: This study aimed to evaluate mortality risk associated with readily accessible laboratory parameters and underlying conditions in hospitalized older adults. Methods: This retrospective study included geriatric patients admitted for inpatient care to the internal medicine wards of two major university hospitals in two different regions of Turkey. Data related to the patients were collected by retrospective review of patient charts and electronic records. Survival data were obtained from the Death Reporting System of the Turkish Ministry of Health. Survival after admission at 30 days and 1 year was noted. Results: The study included 1,465 hospitalized older adults with a median age of 74 years, of whom (51.0%) were women. Of these patients, 115 (7.8%) died within 30 days and 382 (26.1%) died within 12 months. Admission for infectious diseases or palliative support and the presence of malignancy were identified as independent risk factors for both 30-day and 12-month mortality. A 1-unit increase in CCI corresponded to 20% higher odds of both 30-day and 12-month mortality. A 1-unit increase in MPV was associated with 52.5% higher odds of 30-day mortality. A 1-unit increase in CRP was associated with a small but statistically significant 0.6% increase in the odds of 30-day and 12-month mortality. Conclusions: The results of this study show that CCI, CRP, and NLR were associated with higher mortality both at 30 days and 12 months. A 1-unit increase in MPV was associated with 52.5% higher odds of 30-day mortality
... Studies have demonstrated that hyperglycemia considerably interfere the immunity function, which significantly might lead into a poor outcomes among hospitalized patients. [15,21,22] Guan et al stated that DM was the major determinant factor which increase the probability for COVID-19 patients to be admitted in intensive care unit (ICU) with a high mortality rate. [9] Higher inflammation biomarkers, such as high-sensitive C-reactive protein (hs-CRP) and procalcitonin (PCT), has been recorded in diabetic COVID-19 subjects rather than non-diabetic subjects. ...
... Two mechanisms might explain the main finding of decreased CKD and ESRD risks following influenza vaccination in the patients with T2DM. First, acute hyperglycemia episodes mostly occur in patients with severe influenza infection [23]. Infection-induced glycemic deviation can easily enhance acute hyperglycemia in T2DM and thus worsen infection control (known as a vicious circle) [24,25]. ...
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Patients with type 2 diabetes mellitus (T2DM) have a higher risk of chronic kidney disease (CKD) due to vascular complications and chronic inflammation. T2DM contributes to a higher risk of mortality and morbidity related to influenza. In Taiwan, influenza vaccination is recommended for patients with T2DM. A previous meta-analysis reported the efficacy of influenza vaccination in reducing hospitalization and mortality in patients with diabetes; however, the renal protective effect of the vaccine remains unclear. This study evaluated whether influenza vaccination could reduce the incidence of CKD and dialysis in patients with T2DM. The study cohort included all patients aged ≥55 years who were diagnosed as having T2DM between 1 January 2000 and 31 December 2012, by using data from Taiwan’s National Health Insurance Research Database. Each patient was followed up with to assess factors associated with CKD. A time-dependent Cox proportional hazard regression model after adjustment for potential confounders was used to calculate the hazard ratio (HR) of CKD in the vaccinated and unvaccinated patients. The study population comprised 48,017 eligible patients with DM; 23,839 (49.7%) received influenza vaccination and the remaining 24,178 (50.3%) did not. The adjusted HRs (aHRs) for CKD/dialysis decreased in the vaccinated patients compared with the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs: 0.47/0.47, 0.48/0.49, and 0.48/0.48, respectively, all p < 0.0001). We observed similar protective effects against CKD during the influenza and noninfluenza seasons. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor. Furthermore, aHRs for CKD/dialysis were 0.71 (0.65–0.77)/0.77 (0.68–0.87), 0.57 (0.52–0.61)/0.69 (0.56–0.70), and 0.30 (0.28–0.33)/0.28 (0.24–0.31) in the patients who received 1, 2–3, and ≥4 vaccinations during the follow-up period, respectively. This population-based cohort study demonstrated that influenza vaccination exerts a dose-dependent and synergistic protective effect against CKD in the patients with T2DM with associated risk factors.
... 22 Increased blood sugar levels are likely to have a significant impact on the bacterial intracellular breakdown, neutrophil phagocytosis and chemotaxis, and boosting affinity of viral binding and entrance while lowering virus clearance. 23 Furthermore, it has a major impact on proteins by inducing glycosylation and changing complement composition, 24,25 and glycosylation makes cells more vulnerable to viral inflammation and damage. 26,27 Furthermore, endotheliitis could be a trigger for organ malfunction that leads to critical COVID-19 disease, which is exacerbated by endothelial dysfunction combined with chronic hyperglycemia. ...
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Background: It has been documented that the mortality rate in diabetic persons can reach 10%. In addition, it has been shown that the rate of mortality and the need for respiratory support are higher among newly diagnosed cases of diabetes mellitus compared with patients known to have diabetes mellitus for a relatively long duration. In the setting of the pandemic of COVID-19, glycemic control for the patients admitted to hospitals is critical, as is diabetes screening to uncover undiagnosed cases. Aim of the study: To explore the possible link between diabetes mellitus and COVID-19 in Iraq Patients and methods: The current research was carried out in Al-Diwaniyah Province, Iraq, in Al-Diwaniyah Teaching Hospital, including the word of medicine, respiratory unit, and intensive care unit. The study started on Sept 15, 2021 and ended on Apr 15, 2022. The study was cross-sectional and included 100 patients with a diagnosis of COVID-19 evidenced by polymerase chain reaction (PCR) test and CT-scan "computed tomography scan of the chest. Those patients were chosen randomly from the pool of patients visiting the teaching hospital. The age range of patients was between 18 and 94 years, with 45 males and 55 females. Laboratory investigation results were retrieved from patients' records and included random blood sugar, lactate dehydrogenase, d-dimer, HbA1c%, and "C-reactive protein (CRP)." Results: The mean values of age, random blood sugar (RBS), lactate dehydrogenase (LDH), d-dimer, HbA1c, and HS-CRP were comparable between males and females (p > 0.05). Patients with high HbA1c levels (HbA1c ≥ 6.5%) were older and had significantly higher levels of random blood sugar and d-dimer than patients with HbA1c < 6.5%. The d-dimer level showed a significant positive correlation to RBS, LDH, HbA1c, and HS-CRP (p < 0.05). Conclusion: Higher levels of markers of inflammation were associated with HbA1c levels in the diabetic range, indicating a bi-directional relation between diabetes mellitus and the severity of COVID-19.
... The positive correlation between perceived aging and HOMA-IR and insulin level was close to statistical significance (p = 0.07 and p = 0.08 respectively) ( Table 3). Men who were perceived as older than their real age and men who were perceived as younger than their real age did not differ in terms of insulin level (t(114) = − 0. 48 Simple correlation analysis showed also no relationship between glycemic markers levels and perceived age, and perceived aging in women. There was also no relationship between glycemic markers and chronological age (Table 4). ...
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Glycemia is linked with one of the key mechanisms underlying the aging process and inter-individual differences in biological age. Previous research showed that glucose level is linked with perceived age in elder individuals. This study aimed to verify if glycemia is related to perceived facial age in healthy adult individuals as interventions in younger and healthy cohorts are crucial for preventing the onset of age-related diseases. The study sample consisted of 116 healthy men of mean age 35.53 ± 3.54 years (29.95–44.29) and 163 healthy women of mean age 28.38 ± 2.40 (24.25–34.17) years. Glycemia was evaluated by fasting glucose, insulin, HOMA-IR, and glycated hemoglobin level. BMI, facial sexual dimorphism, estradiol, testosterone, and hsCRP levels were controlled. Perceived age was evaluated based on standardized facial photos in an online survey. Additionally perceived facial aging was calculated as a difference between perceived age and chronological age. No relationship between the levels of biochemical indicators of glycemia and perceived facial age or aging was found both in men and women, also when controlled for possible confounders. This study shows that perceived facial age in adult individuals is rather linked with body adiposity of sexual dimorphism but not with glycemic markers.
... Metabolic disorders and DM-related gallstone formation may play a role that is not fully elucidated [21]. Chronically elevated blood sugar levels alter the immune response and render the diabetic more susceptible to infections by various mechanisms, such as glycosylation of the complement proteins, inhibition of immunoglobulin-mediated opsonization of bacteria, inhibition of neutrophil migration phagocytosis, and apoptosis [22][23][24]. Moreover, septic site infection and wound dehiscence were encountered to be more frequent in diabetic patients [25][26][27][28][29]. ...
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Acute cholecystitis, which is usually associated with gallstones is one of the most common surgical causes of emergency hospital admission and may be further complicated by mural necrosis, perforation and abscess formation. Perforation of the gallbladder is a relatively uncommon complication of acute cholecystitis (0.8–3.2% in recent reviews). The intrahepatic perforation causing a liver abscess is an extremely rare condition, anecdotally reported in the scientific literature, even in the rare types of subacute or acute perforation. Liver abscess caused by gallbladder perforation can be a life-threatening complication with a reported mortality of 5.6%. The treatment of synchronous pyogenic liver abscess and acute cholecystitis may be challenging. We reported three cases of liver abscess due to acute cholecystitis in which different therapeutical approaches were employed. The first case was treated with antibiotics and interval laparoscopic cholecystectomy; the second case was treated with emergency cholecystectomy; and the third case with percutaneous aspiration of the abscess only. The appropriate therapeutical method in these cases depends on the patient’s clinical condition, the on-site expertise that is available in the hospital, and the experience of the surgeon.
... Сред пациентите със ЗД най-уязвими са тези с лош гликемичен контрол на заболяването. Хипергликемията стимулира синтеза и освобождаването на ци-токини и е независим рисков фактор за смъртност при COVID-19 [11] . Докладвана е 8% смъртност при диабетно болните с COVID-19 [12] . ...
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The Covid-19 pandemics, which caused significant morbidity and death worldwide, negatively influenced the public health. In the research presented, the age group, the premorbid and laboratory profile of the dead patient with Covid-19 are analyzed, with the idea of identifying the risk factors of unfavorable forecast in the case of infection with SARS-CoV-2. Elderly people with comorbidity are the ones more threatened by a more difficult passing of Covid-19 and a lethal outcome.
... Diabetes can cause a proinflammatory state which leads the upregulated cytokine response with increased level of interleukin-6 (IL-6), also reported in COVID-19. 8 Entry of SARS-CoV2 into a host cell activates an inflammatory response that produces an army of interferon gamma (IFNγ) which results into a cytokine storm. 9 One of the key factors that trigger the process of pathogenesis is cytokine storm which ultimately results in plasma leakage, disseminated vascular coagulation and permeability of vascular membrane detected in COVID-19 patients. ...
Article
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Coronavirus disease 2019 (COVID-19) specifically in diabetic patients has attracted attention worldwide due to the poor prognosis of infection, compromised immunity and delayed response to medicines leading to increased death rate. Several pathophysiological explanations can be linked in support of connection between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) alias COVID-19 and diabetes severity. In patients with diabetes, the innate immune system is compromised and the disease can be triggered by SARS-CoV-2. The exaggerated and inappropriate cytokine response can be evidenced in both diabetic and COVID-19 patients. This is evidenced by the elevated levels of IL-6 in their blood. It has been known that people with diabetes are more prone to having an inflammatory cytokine storm, which can cause acute respiratory distress syndrome (ARDS). Anti-viral drugs and agents can help lower blood sugar levels, but their use should be carefully monitored to see if they can also interact with COVID-19 treatment.
... Hiperglikemia mengubah metabolism netrofil melalui penghambatan G6PD dan aktivasi PKC. Aktivasi PKC menyebabkan penurunan fungsi komplemen, glikosilasi imunoglubulin dan menurunkan fungsinya juga pembentukan struktur tersier C3 (Jafar et al., 2016). ...
... Several risk factors or medical conditions might be associated with an increased risk of developing SA. Half of our patients had a medical history of diabetes mellitus, which by itself increases susceptibility not just for joint infections but for all types of infections due to the effects of hyperglycemia in the body; these could also affect the immune system where it has been found to cause defects on phagocytosis, neutrophil migration, and impaired intracellular killing of microorganisms, among other effects like decreased vascular dilation which affects the initial inflammatory response 26 . Probably, because the knee is the largest joint in the human body, it is also the most commonly affected, as shown in our patients. ...
Article
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Objective: The objective of the study was to determine the added value of synovial fluid (SF) glucose levels and other biochemical parameters as possible biomarkers of bacterial septic arthritis (SA). Materials and methods: We prospectively examined adult patients with SA. As a control group, adults with uninfected joints were enrolled. SF samples were obtained, and microbiological analyses were made. SF glucose levels, pH, and leukocyte esterase were measured using a glucometer and colorimetric test strips. Blood samples were collected from both groups to determine glucose levels. Results: We included eight subjects with knee ligaments lesions, six with meniscus lesions, and five with osteoarthritis as the control group, as well as 20 patients with SA. SF culture was positive in 60%. SF glucose levels from patients were lower than the controls (p = 0.0018) with the lowest concentration in patients with a positive culture (p = 0.0004). Blood and SF glucose concentration from the positive culture patients were compared (p < 0.0001). Leukocyte esterase presented the highest values in patients with a positive culture (p < 0.0001) and a more acidic pH was found compared to the control group (p < 0.0001). Conclusion: These biochemical parameters might be a quick and inexpensive added value for distinguishing between infective and non-infective joint disease.
... 10 Poorly controlled diabetes will impact host resistance to wound infection because elevated blood sugar, even in the short-term, will significantly impact the innate immune response. 11,12 Also, wounds that involve arterial insufficiency have limited access to the host's systemic immunity (i.e., neutrophils), which Bilateral leg venous dermatitis on minimally ambulatory, obese patient with venous insufficiency complicated by general nonadherence to compression recommendations. This inflammation may be mistaken for cellulitis (patient consent was obtained for the use of these photographs) attempt to protect the host from wound infection. ...
Article
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Differentiating acute and chronic wound infections in terms of their microbiological, immunological and clinical characteristics, and their therapeutic strategies.
... 10 Poorly controlled diabetes will impact host resistance to wound infection because elevated blood sugar, even in the short-term, will significantly impact the innate immune response. 11,12 Also, wounds that involve arterial insufficiency have limited access to the host's systemic immunity (i.e., neutrophils), which Bilateral leg venous dermatitis on minimally ambulatory, obese patient with venous insufficiency complicated by general nonadherence to compression recommendations. This inflammation may be mistaken for cellulitis (patient consent was obtained for the use of these photographs) attempt to protect the host from wound infection. ...
Article
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Wound infection is a complex pathology that may manifest either as a rapid onset acute condition, or as a prolonged chronic condition. Although systemic antibiotic therapy is often appropriate and necessary for acute wound infections, it is often used inappropriately, excessively and unsuccessfully in chronic wound infections. Overuse of antibiotics in chronic (hard-to-heal) wound management contributes to antibiotic resistance. This literature review confirms that acute and chronic wound infections are significantly differentiated by their cause (microbial phenotype), the subsequent host immune response and by the resulting clinical manifestations. Consequently, recognition of the type of wound infection followed by appropriate and timely therapy is required to improve wound healing outcomes while encouraging more judicious and responsible use of antibiotics.
... There are several plausible pathophysiological explanations for the connection between diabetes and the occurrence of corona virus-19. As the main line of defense against this infection, a weakened body's defensive system is seen in patients with uncontrolled diabetes [45]. Additionally, as demonstrated in COVID-19 sufferers, diabetes is a pro-inflammatory syndrome characterized by an improper and exaggerated cytokine response, where DM patients had significantly greater amounts of interleukin-6 (IL-6), ferritin, and C-reactive protein in their bloodstream compared non-DM individuals [46]. ...
Article
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Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.
Article
PurposeThis study aimed to characterize postoperative blood glucose fluctuation in patients who underwent esophagectomy for esophageal cancer, and to define its impact on complications and prognosis. Methods The subjects of this retrospective study were 284 patients who underwent esophagectomy at Osaka University Hospital between 2015 and 2017. Data analyzed included clinicopathological background, the immediate postoperative blood glucose level (IPBG), postoperative blood glucose variability (PBGV), insulin dosage, postoperative complications, and prognosis. ResultsThe median IPBG and PBGV were 170 (64–260) mg/dl and 64.5 (11–217) mg/dl, respectively. Postoperative pneumonia was more common in patients with PBGV > 100 mg/dl (P = 0.015). Patients with IPBG < 170 mg/dl had significantly worse 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) than those with IPBG > 170 mg/dl (54.5% vs. 80.4%, respectively, [P < 0.001] and 44.3% vs. 69.3%, respectively, [P = 0.001]). The 5-year OS rates were 43.5%, 68.3%, 80.6%, and 79.0% for patients with IPBG < 154, 154–170, 170–190, and ≥ 190 mg/dl, respectively. The corresponding 5-year RFS rates were 38.1%, 52.4%, 77.0%, and 61.3%, respectively. Multivariate analysis revealed that IPBG < 154 mg/dl and pathological stage were independent poor prognostic factors for OS.ConclusionPBGV was associated with postoperative pneumonia, and low IPBG was an independent poor prognostic factor for patients with esophageal cancer.
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Background: Observational studies suggested that type 2 diabetes mellitus (T2DM) was associated with an increased risk of coronavirus disease 2019 (COVID-19). However, Mendelian randomization (MR) studies in the European population failed to find causal associations, partly because T2DM was pleiotropically associated with body mass index (BMI). We aimed to estimate the causal effects of T2DM on COVID-19 outcomes in the East Asian (EAS) population using a two-sample MR approach. Methods: We obtained summary statistics from a genome-wide association study (GWAS) that included 433,540 EAS participants as the exposure dataset for T2DM risk and from COVID-19 Host Genetics Initiative GWAS meta-analyses (round 7) of EAS ancestry as the outcome dataset for COVID-19 susceptibility (4,459 cases and 36,121 controls), hospitalization (2,882 cases and 31,200 controls), and severity (794 cases and 4,862 controls). As the main MR analysis, we performed the inverse variance weighted (IVW) method. Moreover, we conducted a series of sensitivity analyses, including IVW multivariable MR using summary statistics for BMI from a GWAS with 158,284 Japanese individuals as a covariate. Results: The IVW method showed that the risk of T2DM significantly increased the risk of COVID-19 susceptibility (odds ratio [OR] per log (OR) increase in T2DM, 1.11; 95% confidence interval [CI], 1.02-1.20; P = 0.014) and hospitalization (OR, 1.15; 95% CI, 1.04-1.26; P = 0.005), although the risk of severity was only suggestive. Moreover, IVW multivariable MR analysis indicated that the causal effects of T2DM on COVID-19 outcomes were independent of the effect of BMI. Conclusions: Our MR study indicated for the first time that genetically predicted T2DM is a risk factor for SARS-CoV-2 infection and hospitalized COVID-19 independent of obesity in the EAS population.
Article
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A diabetes COVID-19-fertőzésben a rossz prognózis és a halálozás jelentős rizikófaktora. A nem megfelelő glikémiás kontroll, a nagy vércukor-variabilitás és a társbetegségek bizonyítottan további független rizikótényezőknek tekinthetők a klinikai gyakorlatban. Éppen ezért a vércukorszint és a diabeteshez kapcsolódó társbetegségek fokozott kontrollja kiemelten fontos a szövődmények elkerülése céljából. Az internet gyors fejlődésével párhuzamosan már a pandémia előtt is elkezdődött a diabetesgondozás fokozatos átalakulása. A járványhelyzet azonban új helyzetet elé állította a cukorbetegeket és az egészségügyi ellátókat egyaránt, megnyitva a lehetőséget a digitális alapú ellátás fejlődésének irányába. A pandémia ideje alatt a Magyar Diabetes Társaság számos formában nyújtott támogatást a cukorbetegek telemedicinaalapú gondozásához.
Article
The high systemic blood glucose concentration of hyperglycemic wound microenvironment (WME) severely impedes the disinfection and healing of infected skin wounds. Herein, a WME-activated smart natural product, integrated GOx-GA-Fe nanozyme (GGFzyme), is engineered, which combines a nanozyme and natural enzyme to promote reactive oxygen species (ROS) generation in situ for hyperglycemic wound disinfection. GGFzyme can consume a high concentration of glucose in hyperglycemia wounds and generate H2O2. The conversion of glucose into gluconic acid not avails starvation treatment but reduces the pH of WME to elevate the catalytic activities of both the nanozyme (GA-Fe) and natural enzyme (GOx). And H2O2 is then high efficiently catalyzed into •OH and O2•- in situ to combat pathogenic bacteria and promote wound disinfection. The high catalytic antibacterial capacity and superior biosafety, combined with beneficial WME modulation, demonstrate that GGFzyme is a promising therapeutic agent for hyperglycemic wounds.
Article
Background While international guidelines recommend low doses of systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) clinical practice patterns show significant heterogeneity. Increasing doses of corticosteroids have inconsistently been associated with a greater risk of hyperglycemia. Methods Patients admitted to inpatient services for AECOPD were retrospectively enrolled. Hospitalization corticosteroid doses, daily blood glucose levels, and other markers of corticosteroid excess were collected. Correlative and regression analyses were conducted to assess the relationship between corticosteroid dose and average hospitalization blood glucose. Results Daily corticosteroid dose significantly predicted a higher blood glucose (rs=0.179, p=0.0095; p<0.0028 respectively) and cumulative corticosteroid dose predicted a longer hospital length of stay in bivariate and multivariate analyses (rs=0.679, p<0.0001; p<0.0001 respectively). Patients that experienced hypernatremia, hypokalemia, acute hyperglycemia, and acute hypertension received larger corticosteroid doses than patients that did not experience these complicating events. Conclusions We identified that increasing amounts of corticosteroids administered to inpatients experiencing AECOPD experienced higher average hospitalization blood glucose values, protracted hospitalizations, and other untoward effects.
Article
Background There is limited information about the incidence and risk factors of surgical site infections (SSIs) after coronary artery bypass (CABG) surgeries in the Omani population. Aim To estimate the prevalence and describe possible risk factors of SSIs after CABG surgeries in Oman. Method A retrospective nested case–control design was used to screen 596 patients who underwent CABG surgeries over 2 years (2016–2017) in two tertiary hospitals in Oman. The CDC definition for SSIs was used to identify the infected cases. Results Prevalence rate of SSIs was 17.4% and 17.5% in 2016 and 2017, respectively. The most isolated microorganism was Gram-positive bacteria (45.2%). Risk factors of SSIs include female gender (OR = 3.2, p < 0.001), diabetes (OR = 5.83, p < 0.001), overweight or obese (OR = 2.14, p < 0.05) and shaving technique [using razor shaving] (OR = 8.4, p < 0.001). Readmission rate for the case group was 44.2%. Conclusion The infection rate of SSIs after CABG surgeries in developing countries, such as Oman, is considerably high. There is an urgent need to establish SSIs preventive program at the national level. Frequent and systematic assessment of infection control practices before and after CABG surgeries is fundamental and priority strategy to prevent SSIs.
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Since the discovery of the coronavirus disease 2019 outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ failure, while the co-existence of these two culprits can accelerate the rate of disease progression and magnify the severity of the disease. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidneys, brain, eyes, gastrointestinal system, and bones, and sub-sequent manifestation of multi-system organ failure.
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Background The importance of infection prevention and control (IPC) services to prevent threats from healthcare-associated infections and improve the quality of healthcare delivery is undeniable. However, IPC services across the UK and Ireland have substantial variability in terms of team structures and delivery models. Aim The aim of this study was to define an optimal IPC service in different contexts and settings within the United Kingdom and Ireland. Methods This mixed methods study adopted discussion huddles with IPC teams to explore various components of IPC programmes and services. A Nominal Group technique was then undertaken to achieve a group consensus of what an optimal infection prevention service should look like. Results Five discussion huddles were conducted which included 53 participants in total. Key themes arising were IPC Service Priorities, IPC Service Enablers for Success, and Necessary Skills and Expertise Required for Delivering an Effective IPC Service. For the nominal technique, 45 responses were identified which were determining the key priorities for an effective IPC service and 69 responses for establishing key enablers for success. Discussion These findings supported the development of a conceptual model for designing an optimal infection prevention service, which can be used to develop IPC services at an international, national, regional and local level. A focus is required around implementation of these highlighted enablers, so are effectively embedded into infection prevention and control services, and wider healthcare settings.
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Coronavirus disease 2019 (COVID-19) has affected millions of people across the world. Clinicians and scientists across the globe need all the information of this pandemic on one platform. Today, it is also necessary to find out the association of COVID-19 with various medical comorbidities, and its effect on vulnerable populations that require special medical attention. This information will be helpful for the management of COVID-19. COVID-19: Effects in Comorbidities and Special Populations is a concise and visual reference for information about this viral disease and its relationship with different medical conditions. The book provides comprehensive knowledge covering COVID-19 comorbidities (for example, CVD, Diabetes, lung diseases, etc.), and the incidence in specific groups (for example, children and the elderly). Chapters outline the features and the management of the disease in specific conditions. Key Features: ✓ 12 chapters covering several aspects of COVID-19 management, making this a perfect text book for virologist and medical students ✓ Focused and structured description of different effects of COVID-19 in specific patient groups ✓ Multiple tables and figures which summarizes and highlight important points ✓ Multiple choice questions for learners ✓ Detailed list of references, abbreviations and symbols This book is an essential reference for practicing and training virologists, pulmonologists, medical students and scientists working in research labs, pharmaceutical and biotechnology industries in connection with the control of COVID-19 infection.
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High sugar intake has long been recognized as a potential environmental risk factor for increased incidence of many non-communicable diseases, including obesity, cardiovascular disease, metabolic syndrome, and type 2 diabetes (T2D). Dietary sugars are mainly hexoses, including glucose, fructose, sucrose and High Fructose Corn Syrup (HFCS). These sugars are primarily absorbed in the gut as fructose and glucose. The consumption of high sugar beverages and processed foods has increased significantly over the past 30 years. Here, we summarize the effects of consuming high levels of dietary hexose on rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, inflammatory bowel disease (IBD) and low-grade chronic inflammation. Based on these reported findings, we emphasize that dietary sugars and mixed processed foods may be a key factor leading to the occurrence and aggravation of inflammation. We concluded that by revealing the roles that excessive intake of hexose has on the regulation of human inflammatory diseases are fundamental questions that need to be solved urgently. Moreover, close attention should also be paid to the combination of high glucose-mediated immune imbalance and tumor development, and strive to make substantial contributions to reverse tumor immune escape.
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: The consequences of undermanaged perioperative hyperglycemia are notable and can have a serious impact on adverse postoperative outcomes, especially surgical site infections and periprosthetic joint infections (PJIs). ➤: Preoperative screening of hemoglobin A1c with a goal threshold of <7.45% is ideal. ➤: There are a variety of risk factors that contribute to hyperglycemia that should be considered in the perioperative period, including glucocorticoid use, nutritional factors, patient-specific factors, anesthesia, and surgery. ➤: There are expected trends in the rise, peak, and fall of postoperative blood glucose levels, and identifying and treating hyperglycemia as swiftly as possible are the fundamental aims of treatment and improved glucose control. Performing frequent postoperative blood glucose monitoring (in the post-anesthesia care unit, on the day of surgery at 1700 and 2100 hours, and in the morning of postoperative day 1) should be considered to allow for the early detection of alterations in glucose metabolism. In addition, instituting a postoperative dietary restriction of carbohydrates should be considered. ➤: The use of insulin as a hypoglycemic agent in orthopaedic patients is relatively safe and is an effective means of controlling fluctuating blood glucose levels. Insulin therapy should be administered to treat hyperglycemia at ≥140 mg/dL when fasting and ≥180 mg/dL postprandially. Insulin therapy should be ceased at blood glucose levels of <110 mg/dL; however, monitoring for glycemic dysregulation should be continued. In all cases of complex diabetes, consultation with diabetes specialty services should be considered. ➤: The emerging use of technology, including continuous subcutaneous insulin pump therapy and continuous glucose monitoring, is an exciting area of further research and development as such technology can more immediately detect and correct aberrations in blood glucose levels.
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Since December 2019, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread around the world, causing the coronavirus 2019 (COVID-19) pandemic. From the beginning, SARS-CoV-2 has put a strain on the health system. In fact, many patients have had severe forms of the disease with the need for hospitalization due to respiratory failure. To contain the pandemic, the most widely used approach has been lockdowns. Social restrictions have been reduced thanks to the development of vaccines and targeted therapies. However, fatal events still occur among people at high risk of serious infection, such as patients with concomitant diabetes. Different mechanisms have been proposed to explain the poor prognosis of patients with diabetes and COVID-19, but the specific cause is unclear. It is now known that insulin resistance, inflammation, and cytokine storm are involved. Moreover, SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptors to enter cells. This receptor is expressed on pancreatic beta cells and, during infection, it appears that receptor involvement may induce hyperglycemia in patients with or without diabetes. In this study, we discuss the mechanisms underlying the poor prognosis in people with COVID-19 and diabetes and what may improve the outcome in these patients.
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Introduction: The coronavirus disease 2019 (COVID-19) pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a novel and serious global health threat and has dramatically spread worldwide 1. COVID-19 is transmitted primarily through respiratory droplet and direct contact. At the time of this article's drafting, 188,616,093 conrmed cases and 4,065,804 deaths have been reported worldwide with new conrmed cases and deaths occurring per day Materials And Methods: All COVID-19 patients consecutively admitted to the hospital between June 1, 2020, and July 31, 2021, were collected. The diagnosis and clinical classication (mild, moderate, severe, and critical) of COVID-19 patients were carried out by two independent doctors based on the Guideline of Novel Coronavirus Pneumonia (8 th revised Edition) issued by the Chinese National Health Commission. Result: Among 202 diagnosed COVID-19 patients from June 2020 to July 2021, some patients were excluded for age < 18 years (n = 5), pregnant women (n = 3), combined with malignant tumor (n = 1), no available or incomplete laboratory data (n = 120), no FPG data available at admission (n = 44), and patients diagnosed before June or discharged in August (n = 29) were excluded. Finally, 99 cases were included in the study Conclusion: Higher FPG was an independent predictor of prolonged duration of SARS-CoV-2 RNA shedding/clearance in the present study. Our ndings indicate that screening FPG level is an effective and simple method to evaluate the prognosis of patients with COVID-19, and intervention should be taken in time when patients with FPG ≥ 6:1 mmol/l regardless of a history of diabetes.
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Unlabelled: Periodontal disease often develops in patients with diabetes, and further exacerbated with diabetic complications. It would be clinically important to clarify the relationship between diabetic microvascular diseases and periodontal disease. This study aimed to evaluate the association between periodontal disease and diabetic complications in patients with type 2 diabetes with poor glycemic control. A total of 447 patients with type 2 diabetes hospitalized at Rakuwakai Otowa Hospital, Japan, were initially recruited in this study. After excluding 134 patients who lacked clinical data or were edentulous, 312 were included in our study. The severity of periodontal disease was evaluated based on the average bone resorption rate. Patients with diabetic nephropathy developed severe periodontal disease (multivariate-adjusted odds ratio, 3.00 [95% CI 1.41-5.19]). Diabetic neuropathy was positively associated with the severity of periodontal disease; the multivariate-adjusted odds ratio (95% CI) was 1.62 (0.87‒2.99) for moderate and 4.26 (2.21‒8.20) for severe periodontal disease. In contrast, diabetic retinopathy was linked with moderate periodontal disease (multivariate-adjusted odds ratio 2.23 [95% CI 1.10-4.10]), but not with severe conditions (multivariate-adjusted odds ratio 0.92 [95% CI 0.67-3.07]). In conclusion, periodontal disease, evaluated by average bone resorption rate, was associated with diabetic nephropathy and neuropathy. Supplementary information: The online version contains supplementary material available at 10.1007/s13340-022-00591-0.
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Obesity and insulin dysregulation (ID) are increasingly prevalent conditions in equid populations worldwide. Immune impairment is well described in humans with metabolic dysfunction and is reported but still incompletely understood in horses. This study evaluated the effect of acute induced transient hyperglycemia on apoptosis, phagocytosis and oxidative burst activity of peripheral blood polymorphonuclear cells (PMN) of lean and obese adult horses with or without insulin dysregulation. Seventeen adult horses were allocated into three groups based on their body condition score (BCS) and metabolic status: lean-insulin sensitive (lean-IS), obese-insulin sensitive (obese-IS) and obese-insulin dysregulated (obese-ID). ID was determined by insulin tolerance testing (ITT). Blood glucose elevation was induced through an infeed-oral glucose test (in-feed OGT), and all assessments of PMN functions (apoptosis, phagocytosis and oxidative burst) were done in vitro after isolation from peripheral blood before and 120 min after carbohydrate overload. Results were analyzed using a repeated measures linear mixed model with significance defined at P<0.05. No differences in apoptosis were observed between experimental groups at any time point. Phagocytic capacity was significantly lower at baseline in the obese-ID group but increased in response to glucose administration when compared to the other two groups. Basal reactive oxygen species production in the obese-IS group differed significantly from the lean-IS and obese-ID groups and decreased significantly in response to glucose administration. Results from this study showed that both metabolic status itself, and oral glucose administration, seem to be factors that alter PMN functionality in horses, specifically phagocytosis and oxidative burst.
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Introduction: The newly discovered coronavirus, SARS-CoV-2, with its respective disease, COVID-19, is the cause of the pandemic that was declared on March 11, 2020, by the World Health Organization. On May 1st 2020, Chile exhibited a total of 17.004 confirmed cases and 234 deaths for COVID-19. However, these rates differ from one region of the country to another. Furthermore, due to their psychosocial characteristics, each region was already different before the pandemic. Objective: This study aims to determine the correlation between psycho-socio-demographic variables and COVID-19’s mortality and case fatality rate, for each chilean region, during March and April 2020. Methodology: A correlational study was carried out. The sample corresponded to the projected Chilean population of 2020, based on the 2017 Chilean Census. The sources of data were the Chilean ministerial databases. Through the use of Microsoft Excel® and XLSTAT®, this data was tabulated, analyzed, and then employed to calculate Pearson’s correlation coefficient. Results: One main find was that the average monthly income of the employed presented the highest correlation with the mortality rate, mounting to a correlation coefficient of 0,430. Regarding the case fatality rate, the most significant correlation was exhibited by the incidence of poverty in the population, with a correlation coefficient of 0,468. Discussion: It is important to continue investigating about social determinants that affect the pandemic, regarding both infected and deceased people, in order to establish significant relationships that will help focalize health promotion and COVID-19 prevention efforts, as well as psychosocial support and protection measures.
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AimTo identify predictive factors for surgical site infection (SSI) in patients with type 2 diabetes and develop a prediction tool.Materials and methodsWe retrospectively analyzed the perioperative blood glucose management of 105 patients with type 2 diabetes treated from 2016 to 2018 at Chiba University Hospital. The primary outcome was SSI onset within 30 postoperative days; moreover, predictive factors were identified using univariate analysis. Principal component analysis and logistic regression analysis were performed to prepare SSI predictive model using the identified predictive factors. The area under the receiver operating characteristic curve (AUC) was evaluated. Based on the predictive model, we developed a risk engine for SSI prediction.ResultsCompared with patients without SSI (n = 70), those with SSI (n = 35) had significantly higher fasting blood glucose levels at referral (169.1 ± 61.8 mg/dL vs. 140.1 ± 56.6, P = 0.036), preoperative mean blood glucose levels (178.3 ± 48.4 mg/dL vs. 155.2 ± 39.7, P = 0.009), preoperative maximum blood glucose levels (280.4 ± 87.3 mg/dL vs. 230.3 ± 92.4, P = 0.009), preoperative blood glucose fluctuations (54.9 ± 24.1 mg/dL vs. 37.7 ± 23.1, P = 0.001), percentage of hospitalization at referral (54.3% vs. 20.0, P < 0.001); longer operation time (432.5 ± 179.6 min vs. 282.5 ± 178.3, P < 0.001); and greater bleeding volume (972.3 ± 920.1 mg/dL vs. 436.4 ± 795.8, P < 0.001). Logistic regression analysis revealed preoperative blood glucose fluctuation and operation time as the most reliable predictive factors. The predictive model had high prediction accuracy (AUC of 0.801). The risk engine prototype for SSI prediction can be accessed at https://www.dm-ope-riskengine.org/.Conclusions The predictive model developed in this study could screen high-risk patients. It may be useful to prevent SSI in such patients.
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Hyperglycemia from diabetes is associated with increased risk of infection from S. aureus and increased severity of illness. Previous work in our laboratory demonstrated that elevated glucose (>6 mM) dramatically inhibited S. aureus-initiated complement-mediated immune effectors. Here we report in vivo studies evaluating the extent to which a hyperglycemic environment alters complement-mediated control of S. aureus infection in a rat peritonitis model. Rats were treated with streptozocin to induce diabetes or sham-treated and then inoculated i.p. with S. aureus. Rats were euthanized and had peritoneal lavage at 2 or 24 hours after infection to evaluate early and late complement-mediated effects. Hyperglycemia decreased the influx of IgG and complement components into the peritoneum in response to S. aureus infection and decreased anaphylatoxin generation. Hyperglycemia decreased C4-fragment and C3-fragment opsonization of S. aureus recovered in peritoneal fluids, compared with euglycemic or insulin-rescued rats. Hyperglycemic rats showed decreased phagocytosis efficiency compared with euglycemic rats, which correlated inversely with bacterial survival. These results suggest that hyperglycemia inhibited humoral effector recruitment, anaphylatoxin generation, and complement-mediated opsonization of S. aureus, suggesting that hyperglycemic inhibition of complement effectors may contribute to the increased risk and severity of S. aureus infections in diabetic patients.
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Postprandial hyperglycemia induces inflammation and endothelial dysfunction resulting in vascular complications in patients with diabetes. Toll-like receptors (TLRs) are central to the regulation of inflammatory responses through activation of nuclear factor-kappa B (NF-ĸB). This study examined the role of TLR2 and 4 in regulating inflammation and endothelial dysfunction when exposed to fluctuating glucose concentrations. HMEC-1 cells (a human microvascular endothelial cell line) were exposed to control (5 mM), 30 mM (high), fluctuating (5/30 mM) and 11.2 mM glucose (approximate glycaemic criteria for the diagnosis of diabetes mellitus) for 72 h. Cells were assessed for TLR2, 4, high mobility group box -1 (HMGB1), NF-ĸB, monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Fluctuating glucose concentrations maximally upregulated TLR4 but not TLR2 expression with increased NF-ĸB activation, IL-8 and ICAM-1 expression. HMGB1 was increased in the supernatants of cells exposed to 30 mM and 11.2 mM glucose compared to control. The addition of recombinant HMGB1 induced NF-ĸB activation and synthesis of proinflammatory cytokines and chemokines, which were prevented by TLR2 or 4 signalling inhibition. An additive effect when both TLR2 and 4 signalling pathways were inhibited was observed. However, only inhibition of TLR4 signalling suppressed the synthesis of MCP-1, IL-8 and ICAM-1. In vivo, streptozotocin-induced diabetic mice exhibited an increase in glomerular ICAM-1 which was not evident in TLR2-/- or TLR4-/- diabetic mice. Collectively, our results suggest that targeting the signalling pathway of TLR2 and 4 may be of therapeutic benefit in attenuating vascular inflammation in diabetic microangiopathy.
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Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.
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The blood glucose target range and optimal method to reach this range remain a matter of debate in the intensive care unit (ICU). A computer decision support system (CDSS) might improve the outcome of ICU patients through facilitation of a tighter blood glucose control. We conducted a multi-center randomized trial in 34 French ICU. Adult patients expected to require treatment in the ICU for at least 3 days were randomly assigned without blinding to undergo tight computerized glucose control with the CDSS (TGC) or conventional glucose control (CGC), with blood glucose targets of 4.4-6.1 and <10.0 mmol/L, respectively. The primary outcome was all-cause death within 90 days after ICU admission. Of the 2,684 patients who underwent randomization to the TGC and CGC treatment groups, primary outcome was available for 1,335 and 1,311 patients, respectively. The baseline characteristics of these treatment groups were similar in terms of age (61 ± 16 years), SAPS II (51 ± 19), percentage of surgical admissions (40.0 %) and proportion of diabetic patients (20.3 %). A total of 431 (32.3 %) patients in the TGC group and 447 (34.1 %) in the CGC group had died by day 90 (odds ratio for death in the TGC 0.92; 95 % confidence interval 0.78-1.78; p = 0.32). Severe hypoglycemia (<2.2 mmol/L) occurred in 174 of 1,317 patients (13.2 %) in the TGC group and 79 of 1,284 patients (6.2 %) in the CGC group (p < 0.001). Tight computerized glucose control with the CDSS did not significantly change 90-day mortality and was associated with more frequent severe hypoglycemia episodes in comparison with conventional glucose control.
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Chronic hyperglycemia is an established risk factor for endothelial damage. It remains unclear, however, whether brief hyperglycemic exposure exacerbates the damage to vascular endothelial cells induced by endotoxin. We hypothesize that brief hyperglycemic exposure enhances the permeability of the endothelium following stimulation with lipopolysaccharide (LPS). Correlations between modulation of nitric oxide synthase (NOS) pathways and altered endothelial homeostasis have been studied and demonstrated in various pathophysiological conditions. NOS activities are regulated by endogenous inhibitors, including asymmetric dimethylarginine (ADMA), which is metabolized by dimethylarginine dimethylaminohydrolase (DDAH). Since previous data demonstrated that endothelial dysfunction may be related to reduced expression and/or activity of DDAH, in this study, we aimed to determine the effect of increased glucose levels on pulmonary microvascular endothelial cell (PMVEC) permeability, including effects on the NOS pathways. Human PMVECs were incubated with normal (5.5 mM) and high (33 mM) concentrations of D-glucose for 5 days to create a monolayer of cells prior to LPS stimulation (10 μg/ml) for 12 h. When stimulated with LPS, cells incubated with a high glucose (HG) concentration had significant microfilament rearrangement compared with cells incubated with a normal glucose concentration, as determined by immunofluorescence. Scanning electron microscopy revealed a larger average diameter and increased number of fenestrae on the hyperglycemic PMVECs when stimulated with LPS, compared with PMVECs cultured with a normal glucose concentration. The results demonstrated that a high concentration of glucose increases the LPS-stimulated horseradish peroxidase (HRP) permeability compared with a normal concentration of glucose. Furthermore, a HG concentration upregulated LPS-stimulated inducible NOS (iNOS) production and down-regulated endothelial NOS (eNOS) and DDAH-2 expression. Hyperglycemia significantly increased LPS-stimulated nitrite/nitrate production (stable NO end-products). Our results, thus, demonstrate that in vitro HG concentrations exacerbate LPS-stimulated cytoskeletal rearrangement and hyperpermeability of an endothelial monolayer, and cause further imbalance of the NO pathway. These results suggest that it is important to manage even short-term increases in blood glucose, particularly following acute infection.
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Diabetes confers an increased propensity to atherosclerosis. Inflammation is pivotal in atherogenesis, and diabetes is a proinflammatory state. Interleukin (IL)-6, in addition to inducing the acute-phase response, contributes to insulin resistance. Monocytes from type 2 diabetic patients secrete increased IL-6. The aim of this study was to examine molecular mechanisms for increased IL-6 release from monocytes under hyperglycemia. Monocytic cells (THP-1) were cultured in the presence of 5.5 mmol/l (normal) or 15 mmol/l (high) glucose and mannitol. Secreted IL-6, intracellular IL-6, and IL-6 mRNA were significantly increased with hyperglycemia (P < 0.001). Incubation of cells with inhibitors of reactive oxygen species failed to affect high-glucose-induced IL-6 release. Pan-protein kinase C (PKC) inhibitors significantly decreased high-glucose-induced IL-6 release. A specific inhibitor of p38 mitogen-activated protein kinase (MAPK; SB 202190), but not the extracellular signal-regulated kinase inhibitor PD98059, significantly decreased high-glucose-induced IL-6 release. Furthermore, the PKC-alpha/beta2 inhibitor decreased p38MAPK and the resulting high-glucose-induced IL-6 release. Both antisense oligos to PKC-beta and -alpha as well as small interfering RNA (siRNA) to PKC-alpha and -beta resulted in significantly decreased high-glucose-induced IL-6 release. Nuclear factor-kappaB (NF-kappaB) inhibitors significantly decreased IL-6 mRNA and protein. siRNA to PKC-beta and -alpha also significantly decreased NF-kappaB activity and IL-6 release. The combination was not additive to either siRNA alone, suggesting that they work through a common pathway. Thus, IL-6 release from monocytes under hyperglycemia appears to be mediated via upregulation of PKC, through p38MAPK and NF-kappaB, resulting in increased mRNA and protein for IL-6. Thus, inhibition of PKC-alpha and -beta can ameliorate the proinflammatory state of diabetes.
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It is well recognized that poor perioperative blood glucose (BG) control can increase the risk of infection, cardiovascular accidents, and even death in patients undergoing cardiac surgery. Since it has been reported that tight BG control (80-110 mg/dL) yields better outcomes in critically ill patients, it became a standard of care to control BG using intravenous insulin infusion in ICU. However, it has been debated in terms of the optimal target range whether a strict control with intensive insulin therapy is better than liberal control. Because strict BG control can often cause hypoglycemia, which in turn increases the hospital mortality. In fact, a meta-analysis of randomized clinical trials concluded that tight BG control was not associated with significantly reduced hospital mortality but was associated with an increased risk of hypoglycemia. According to the current published guidelines, it seems to be optimal to control BG level of 140-180 mg/dL in ICU. In terms of more strict BG control (110-140 mg/dL), it may be appropriate in selected patients as long as this can be achieved without significant hypoglycemia.
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Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed "NETosis." Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.
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In general, infectious diseases are more frequent and/or serious in patients with diabetes mellitus, which potentially increases their morbimortality. The greater frequency of infections in diabetic patients is caused by the hyperglycemic environment that favors immune dysfunction (e.g., damage to the neutrophil function, depression of the antioxidant system, and humoral immunity), micro- and macro-angiopathies, neuropathy, decrease in the antibacterial activity of urine, gastrointestinal and urinary dysmotility, and greater number of medical interventions in these patients. The infections affect all organs and systems. Some of these problems are seen mostly in diabetic people, such as foot infections, malignant external otitis, rhinocerebral mucormycosis, and gangrenous cholecystitis. In addition to the increased morbidity, infectious processes may be the first manifestation of diabetes mellitus or the precipitating factors for complications inherent to the disease, such as diabetic ketoacidosis and hypoglycemia. Immunization with anti-pneumococcal and influenza vaccines is recommended to reduce hospitalizations, deaths, and medical expenses.
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Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of the host defense complement system in controlling bacterial pathogens in hyperglycemic environments. The interactions of complement C3 with bacteria in elevated glucose were assayed for complement activation to opsonic forms, phagocytosis and bacterial killing. C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry to measure glycation and structural differences. Elevated glucose inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by neutrophils were both decreased in elevated glucose conditions. Interestingly, elevated glucose increased the binding of unactivated C3 to S. aureus, which was reversible on return to normal glucose concentrations. In a model of polymicrobial infection, S. aureus in elevated glucose conditions depleted C3 from serum resulting in decreased complement-mediated killing of E. coli. To investigate the effect of differing glucose concentration on C3 structure and glycation, purified C3 incubated with varying glucose concentrations was analyzed by mass spectrometry. Glycation was limited to the same three lysine residues in both euglycemic and hyperglycemic conditions over one hour, thus glycation could not account for observed changes between glucose conditions. However, surface labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface availability of seven lysine residues in response to increasing glucose concentrations. These results suggest that the tertiary structure of C3 changes in response to hyperglycemic conditions leading to an altered interaction of C3 with bacterial pathogens. These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological control of S. aureus. Mass spectrometric analysis reveals that the glycation state of C3 is the same regardless of glucose concentration over a one-hour time period. However, in conditions of elevated glucose C3 appears to undergo structural changes.
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Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
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Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown. In a prospective, randomized, controlled study of adult patients admitted to our medical ICU, we studied patients who were considered to need intensive care for at least three days. On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]). There was a history of diabetes in 16.9 percent of the patients. In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P=0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P=0.009) and morbidity was also reduced. Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified before therapy. Further studies are needed to confirm these preliminary data. (ClinicalTrials.gov number, NCT00115479.)
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The effect of intensive therapy to achieve tight glycemic control in patients hospitalized in non-critical care settings is unclear. We conducted a systematic review and meta-analysis to determine the effect of intensive glycemic control strategies on the outcomes of death, stroke, myocardial infarction, incidence of infection, and hypoglycemia. We included randomized and observational studies. Bibliographic databases were searched through February 2010. Random effects model was used to pool results across studies. Nineteen studies (nine randomized and 10 observational studies) were included. The risk of bias across studies was moderate. Meta-analysis demonstrates that intensive glycemic control was not associated with significant effect on the risk of death, myocardial infarction, or stroke. There was a trend for increased risk of hypoglycemia (relative risk, 1.58; 95% confidence interval, 0.97-2.57), particularly in surgical studies and when the planned glycemic target was achieved. Intensive glycemic control was associated with decreased risk of infection (relative risk, 0.41; 95% confidence interval, 0.21-0.77) that was mainly derived from studies in surgical settings. Intensive control of hyperglycemia in patients hospitalized in non-critical care settings may reduce the risk of infection. The quality of evidence is low and mainly driven by studies in surgical settings.
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A dysregulated immune response and functional immunosuppression have been considered the major mechanisms of the bacterial sepsis syndrome. More recently, the loss of endothelial barrier function and resultant microvascular leak have been found to be a key determinant of the pathogenesis of bacterial sepsis. Whether a similar paradigm applies to systemic viral syndromes is not known. Answering this question has far-reaching implications for the development of future anti-viral therapeutic strategies. In this review, we provide an overview of the structure and function of the endothelium and how its barrier integrity is compromised in bacterial sepsis. The various in vitro and in vivo methodologies available to investigate vascular leak are reviewed. Emphasis is placed on the advantages and limitations of cell culture techniques, which represent the most commonly used methods. Within this context, we appraise recent studies of three viruses - hantavirus, human herpes virus 8 and dengue virus - that suggest microvascular leak may play a role in the pathogenesis of these viral infections. We conclude with a discussion of how endothelial barrier breakdown may occur in other viral infections such as H5N1 avian influenza virus.
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