Hyperglycemia Affects the Expression of Inflammatory Genes in Peripheral Blood Mononuclear Cells of Patients with Type 2 Diabetes

Akbari, M; Hassan‐Zadeh, Vahideh

doi:10.1080/08820139.2018.1480031

Cited by 24 publications

(13 citation statements)

References 40 publications

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“…diabetes, our study did not show significant differences in IL-1-induced responses between type 1 diabetes and healthy control participants. This may be due to differences in experimental design or to unique phenotypic characteristics present in the peri-diagnostic period [53,54]. It is also possible that there is, in fact, a difference in IL-1-induced responses, but that our study was not sufficiently powered to detect them.…”

Section: Discussionmentioning

confidence: 94%

Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes

et al. 2020

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Aims/hypothesis Self-antigen-specific T cell responses drive type 1 diabetes pathogenesis, but alterations in innate immune responses are also critical and not as well understood. Innate immunity in human type 1 diabetes has primarily been assessed via gene-expression analysis of unstimulated peripheral blood mononuclear cells, without the immune activation that could amplify disease-associated signals. Increased responsiveness in each of the two main innate immune pathways, driven by either type 1 IFN (IFN-1) or IL-1, have been detected in type 1 diabetes, but the dominant innate pathway is still unclear. This study aimed to determine the key innate pathway in type 1 diabetes and assess the whole blood immune stimulation assay as a tool to investigate this. Methods The TruCulture whole blood ex vivo stimulation assay, paired with gene expression and cytokine measurements, was used to characterise changes in the stimulated innate immune response in type 1 diabetes. We applied specific cytokine-induced signatures to our data, pre-defined from the same assays measured in a separate cohort of healthy individuals. In addition, NOD mice were stimulated with CpG and monocyte gene expression was measured. Results Monocytes from NOD mice showed lower baseline vs diabetes-resistant B6.g7 mice, but higher induced IFN-1associated gene expression. In human participants, ex vivo whole blood stimulation revealed higher induced IFN-1 responses in type 1 diabetes, as compared with healthy control participants. In contrast, neither the IL-1-induced gene signature nor response to the adaptive immune stimulant Staphylococcal enterotoxin B were significantly altered in type 1 diabetes samples vs healthy control participants. Targeted gene-expression analysis showed that this enhanced IFN response was specific to IFN-1, as IFN-γ-driven responses were not significantly different. Conclusions/interpretation Our study identifies increased responsiveness to IFN-1 as a feature of both the NOD mouse model of autoimmune diabetes and human established type 1 diabetes. A stimulated IFN-1 gene signature may be a potential biomarker for type 1 diabetes and used to evaluate the effects of therapies targeting this pathway. Kameron B. Rodrigues and Matthew J. Dufort contributed equally to this study.

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Section: Discussionmentioning

confidence: 94%

Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes

et al. 2020

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“…There are two main causes why increased levels of glycaemia, notably in acute states, is associated with adverse prognosis during COVID-19 infection. The first one is that an elevated blood glucose is associated with a significant increase of inflammatory mediators [ 37 ]; Understanding the role of cytokine storming and progressed states of COVID-19 infection [ 38 ] will emphasize how important it is to be alert to patient’s blood glucose and subsequent induced cytokine release. The second reason is the virus attachment to angiotensin converting enzyme 2 (ACE2) [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The impact of metabolic syndrome on morbidity and mortality among intensive care unit admitted COVID-19 patients

Alamdari

Rahimi

Afaghi

et al. 2020

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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Background and aims Given the limited information describing the connection between metabolic syndrome (MetS) and Coronavirus Disease 2019 (COVID-19), we aimed to assess the impact of MetS on morbidity and mortality among COVID-19 patients. Methods This retrospective cohort study was performed from 1st April to May 3, 2020 on 157 ICU-admitted COVID-19 patients in Shahid Modarres Hospital in Tehran, Iran. Patients’ clinical, laboratory and radiological findings, and subsequent complications, were collected and compared between MetS and non-MetS groups. Results 74 of all cases had MetS. Among the MetS components, waist circumference (p-value = 0.006 for men; p-value<0.0001 for women), Triglycerides (p-value = 0.002), and Fasting Blood Sugar (p-value = 0.007) were significantly higher in MetS group; with no statistical difference found in HDL levels (p-value = 0.21 for men; p-value = 0.13 for women), systolic blood pressure(p-value = 0.07), and diastolic blood pressure (p-value = 0.18) between two groups. Length of ICU admission (p-value = 0.009), the need for invasive mechanical ventilation (p-value = 0.0001), respiratory failure (p-value = 0.0008), and pressure ulcers (p-value = 0.02) were observed significantly more in MetS group. The Odds Ratio (OR) of mortality with 0(OR = 0.3660), 1(OR = 0.5155), 2(OR = 0.5397), 3(OR = 1.9511), 4(OR = 5.7018), and 5(OR = 8.3740) MetS components showed an increased mortality risk as the components’ count increased. The patient with BMI>40 (OR = 6.9368) had more odds of fatality comparing to those with BMI>35 (OR = 4.0690) and BMI>30 (OR = 2.5287). Furthermore, the waist circumference (OR = 8.31; p-value<0.0001) and fasting blood sugar (OR = 2.4588; p-value = 0.0245) were obtained by multivariate logistic regression as independent prognostic factors for mortality. Conclusion The findings suggest a strong relationship between having MetS and increased risk of severe complications and mortality among COVID-19 ICU-admitted patients.

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“…Hyperglycemia also causes inflammation [72] via increasing obesity [73], gut permeability [74], and LDL levels in humans [75]. Inflammatory markers like NFKB, TNF-α, IL-6, and IL-18 levels were elevated in hyperglycemic patients [76,77,78,79]. Inflammation is strongly correlated with various cancers [80,81].…”

Section: Hyperglycemia and Risk Factors For Cancermentioning

confidence: 99%

Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality

Ramteke

Deb

Shepal

et al. 2019

Cancers

109

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Cancer and diabetes are amongst the leading causes of deaths worldwide. There is an alarming rise in cancer incidences and mortality, with approximately 18.1 million new cases and 9.6 million deaths in 2018. A major contributory but neglected factor for risk of neoplastic transformation is hyperglycemia. Epidemiologically too, lifestyle patterns resulting in high blood glucose level, with or without the role of insulin, are more often correlated with cancer risk, progression, and mortality. The two conditions recurrently exist in comorbidity, and their interplay has rendered treatment regimens more challenging by restricting the choice of drugs, affecting surgical consequences, and having associated fatal complications. Limited comprehensive literature is available on their correlation, and a lack of clarity in understanding in such comorbid conditions contributes to higher mortality rates. Hence, a critical analysis of the elements responsible for enhanced mortality due to hyperglycemia-cancer concomitance is warranted. Given the lifestyle changes in the human population, increasing metabolic disorders, and glucose addiction of cancer cells, hyperglycemia related complications in cancer underline the necessity for further in-depth investigations. This review, therefore, attempts to shed light upon hyperglycemia associated factors in the risk, progression, mortality, and treatment of cancer to highlight important mechanisms and potential therapeutic targets.

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Hyperglycemia Affects the Expression of Inflammatory Genes in Peripheral Blood Mononuclear Cells of Patients with Type 2 Diabetes

Cited by 24 publications

References 40 publications

Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes

Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes

The impact of metabolic syndrome on morbidity and mortality among intensive care unit admitted COVID-19 patients

Hyperglycemia Associated Metabolic and Molecular Alterations in Cancer Risk, Progression, Treatment, and Mortality

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