Diabetes and infection: assessing the association with glycaemic control in population-based studies

Pearson‐Stuttard, Jonathan; Blundell, Samkeliso; Harris, Tess; Cook, Derek G; Critchley, Julia

doi:10.1016/s2213-8587(15)00379-4

Cited by 243 publications

(212 citation statements)

References 63 publications

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“…Interestingly, this study found no evidence that increased rates of antibiotic prescribing conferred any benefit to smokers 30 . Whilst few clinicians would question the fact that patients with diabetes are at increased risk of infection, 31 there are a range of other comorbidities, such as cardiovascular disease or obesity, that may also be considered when making the clinical decision to prescribe an antibiotic 17 . There is a real need for more granular research studies to advance our understanding of whether higher rates of antibiotic use in patients with comorbidity are primarily driven by diagnostic uncertainty, exemplified by the dilemma of whether to prescribe antibiotics for an infective exacerbation of COPD, or by concerns about an overall increased susceptibility to infection in patients with comorbidities such as diabetes.…”

Section: Discussionmentioning

confidence: 65%

Antibiotic prescribing frequency amongst patients in primary care: a cohort study using electronic health records

Shallcross¹,

Beckley

Rait

et al. 2017

Journal of Antimicrobial Chemotherapy

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Background: Reducing inappropriate antibiotic prescribing in primary care is a public health priority. Objectives: We hypothesized that a subset of patients account for the majority of antibiotic prescriptions in primary care. We investigated the relationship between the total amount of antibiotics prescribed, individual-level antibiotic use and comorbidity. Methods: This was a cohort study using electronic health records from 1 948 390 adults registered with 385 primary care practices in the UK in 2011–13. We estimated the average number of antibiotic prescriptions per patient and the association between prescribing and comorbidity. We modelled the impact on total prescribing of reducing antibiotic use in those prescribed antibiotics most frequently. Results: On average 30.1% (586 194/1 948 390) of patients were prescribed at least one antibiotic per year. Nine percent (174 602/1 948 390) of patients were prescribed 53% (2 091 496/3 922 732) of the total amount of antibiotics, each of whom received at least five antibiotic prescriptions over 3 years. The presence of any comorbidity increased the prescribing rate by 44% [adjusted incidence rate ratio (IRR) 1.44, 95% CI 1.43–1.45]; rates of prescribing to women exceeded those in men by 62% (adjusted IRR 1.62, 95% CI 1.62–1.63). Conclusions: Half of antibiotics prescribed to adults in primary care were for <10% of patients. Efforts to tackle antimicrobial resistance should consider the impact of this on total prescribing.

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Section: Discussionmentioning

confidence: 65%

Antibiotic prescribing frequency amongst patients in primary care: a cohort study using electronic health records

Shallcross¹,

Beckley

Rait

et al. 2017

Journal of Antimicrobial Chemotherapy

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“…Under this perspective, it could be suggested that the use of therapeutically doses of MET in healthy patient could increase AMPK activity, inhibiting the HMGCR function generating a beneficial effects during DENV infection. This suggesting can not be extrapolated to type 2 diabetes patients treated with MET because present evidence indicates that diabetes per se , adversely influence the clinical presentation of any infection because patients have dysfunction in several organs and systems [91] and impairment in host defenses mechanisms [92]. Specifically, type 2 diabetes patients have endothelial dysfunction, which can condition more severe forms of dengue infection[93].…”

Section: Discussionmentioning

confidence: 99%

DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target

Soto-Acosta¹,

et al. 2017

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Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK. AMPK activation by metformin declined the HMGCR activity suggesting that AMPK inactivation mediates the enhanced activity of HMGCR. A reduction on AMPK phosphorylation activity was observed in DENV infected cells at 12 and 24 hpi. HMGCR and cholesterol co-localized with viral proteins NS3, NS4A and E, suggesting a role for HMGCR and AMPK activity in the formation of DENV replicative complexes. Furthermore, metformin and lovastatin (HMGCR inhibitor) altered this co-localization as well as replicative complexes formation supporting that active HMGCR is required for replicative complexes formation. In agreement, metformin prompted a significant dose-dependent antiviral effect in DENV infected cells, while compound C (AMPK inhibitor) augmented the viral genome copies and the percentage of infected cells. The PP2A activity, the main modulating phosphatase of HMGCR, was not affected by DENV infection. These data demonstrate that the elevated activity of HMGCR observed in DENV infected cells is mediated through AMPK inhibition and not by increase in PP2A activity. Interestingly, the inhibition of this phosphatase showed an antiviral effect in an HMGCR-independent manner. These results suggest that DENV infection increases HMGCR activity through AMPK inactivation leading to higher cholesterol levels in endoplasmic reticulum necessary for replicative complexes formation. This work provides new information about the mechanisms involved in host lipid metabolism during DENV replicative cycle and identifies new potential antiviral targets for DENV replication.

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“…In healing wounds, infections are resolved, followed by the establishment of granulation tissue formation and the progression of growth to complete wound closure . The host immune system uses the ability of macrophages, the primary innate immune cells, to kill infiltrating pathogens.…”

Section: Introductionmentioning

confidence: 99%

Human macrophage response to microbial supernatants from diabetic foot ulcers

Deusenbery

Kalan

Meisel

et al. 2019

Wound Repair Regeneration

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Diabetic foot ulcers (DFUs) are a major clinical problem exacerbated by prolonged bacterial infection. Macrophages, the primary innate immune cells, are multifunctional cells that regulate diverse processes throughout multiple phases of wound healing. To better understand the influence of microbial species on macrophage behavior, we cultured primary human monocyte‐derived macrophages from four donors for 24 hours in media conditioned by bacteria and fungi (Pseudomonas aeruginosa, Corynebacterium amycolatum, Corynebacterium striatum, Staphylococcus aureus, Staphylococcus simulans, and Candida albicans) isolated from the DFUs of six patients. The effects of these microbe‐derived signals on macrophage behavior were assessed by measuring the gene expression of a panel of 25 genes related to macrophage phenotype, angiogenesis, bacterial recognition, and cell survival, as well as secretion of two inflammatory cytokines using NanoString multiplex analysis. Principal component analysis showed that macrophage gene expression and protein secretion were affected by both microbial species as well as human donor. S. simulans and C. albicans caused up‐regulation of genes associated with a proinflammatory (M1) phenotype, and P. aeruginosa caused an increase in the secretion of the proinflammatory cytokine and M1 marker tumor necrosis factor‐alpha (TNFα). Together, these results suggest that macrophages respond to secreted factors from microbes by up‐regulating inflammatory markers, and that the effects are strongly dependent on the monocyte donor. Ultimately, increased understanding of macrophage–microbe interactions will lead to the development of more targeted therapies for DFU healing.

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Diabetes and infection: assessing the association with glycaemic control in population-based studies

Cited by 243 publications

References 63 publications

Antibiotic prescribing frequency amongst patients in primary care: a cohort study using electronic health records

Antibiotic prescribing frequency amongst patients in primary care: a cohort study using electronic health records

DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target

Human macrophage response to microbial supernatants from diabetic foot ulcers

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