Role of neutrophils in type 2 diabetes and associated atherosclerosis

Keeter, W. Coles; Moriarty, Alina; Galkina, Elena

doi:10.1016/j.biocel.2021.106098

Cited by 8 publications

(7 citation statements)

References 50 publications

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“… 6 , 7 Various kinds of neutrophil-related abnormalities, such as neutrophilia and a greater abundance of reactive oxygen species (ROS), have been identified in patients with type 2 diabetes mellitus (T2DM). 20 , 21 Neutrophils promote greater peripheral insulin resistance through adipose tissue inflammation. Abnormal neutrophil ROS generation exacerbates endothelial dysfunction and plaque instability, which play roles in the development of ACS.…”

Section: Patient Historymentioning

confidence: 99%

“…Abnormal neutrophil ROS generation exacerbates endothelial dysfunction and plaque instability, which play roles in the development of ACS. 20 Insulin resistance also contributes to low HDLcholesterol concentrations, and both predispose toward the development of diabetes. In addition, hyperglycaemia can lead to the formation of dysfunctional HDL in patients with T2DM 22 .…”

Section: Patient Historymentioning

confidence: 99%

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Utility of neutrophil-to-high-density lipoprotein-cholesterol ratio in patients with coronary artery disease: a narrative review

et al. 2023

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The neutrophil-to-high-density lipoprotein-cholesterol ratio (NHR) is thought to reflect inflammatory status and dyslipidaemia, both of which play significant roles in coronary artery disease (CAD). The objective of this narrative review is to summarise the results of studies that have explored the utility of NHR for the diagnosis and management of CAD. The PubMed, Google Scholar, Scopus, Embase and Web of Science databases were searched for articles related to NHR from their inception to October 2022. Seven relevant articles were obtained for review. There were unclear relationships of NHR with age, sex, smoking status, hypertension and diabetes. However, NHR had a sensitivity and specificity as high as 94.8% and 59%, respectively, for the identification of significant coronary stenosis. NHR was also a superior predictor of prognosis to conventional parameters. NHR had a sensitivity and specificity as high as 77.6% and 74.2%, respectively, for the prediction of adverse events, including mortality, associated with acute coronary syndrome. Thus, NHR could be used in clinical cardiovascular medicine for risk stratification and the prediction of the short-term and long-term outcomes of CAD. However, more studies are required before a quantitative assessment of the efficacy of NHR for use in patient management can be completed.

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Section: Patient Historymentioning

confidence: 99%

Section: Patient Historymentioning

confidence: 99%

Utility of neutrophil-to-high-density lipoprotein-cholesterol ratio in patients with coronary artery disease: a narrative review

et al. 2023

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“…Besides being the most common and debilitating metabolic disorder, type 2 diabetes mellitus is also associated with chronic, low-grade inflammatory burden [ 5 ]. For example, Keeter et al emphasized the role of neutrophils, the most common leukocyte type in the bloodstream, in type 2 diabetes mellitus and in its atherosclerotic complications [ 6 ]. Insulin resistance in type 2 diabetes patients is responsible of the production and release of several cytokines, leading to the hepatic overproduction of acute phase proteins such as C- reactive protein, serum amyloid A, and plasminogen activator inhibitor-1 [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Association between the Prognostic Nutritional Index and Chronic Microvascular Complications in Patients with Type 2 Diabetes Mellitus

Aktas

2023

JCM

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The prognostic nutritional index (PNI) is associated with inflammatory conditions. Since type 2 diabetes mellitus (T2DM) and its microvascular complications produce a significant inflammatory burden, we aimed to compare the PNI levels of the subjects with T2DM to those of healthy individuals. Furthermore, we aimed to compare the PNI levels of the diabetic subjects, with and without microvascular complications. The study cohort consisted of T2DM patients and healthy volunteers. The general characteristics, laboratory data, and PNI of the T2DM and control groups were compared. We further compared the PNI levels of the diabetic patients, with and without diabetic microvascular complications. The PNI levels of the T2DM patients and the control group were 51.6 (30.1–73.8)% and 64.8 (49.4–76)%, respectively (p < 0.001). Subgroup analyses revealed that the PNI was lower in the diabetic subjects with diabetic microvascular complications than in the diabetic patients without microvascular complications (p < 0.001), in patients with diabetic nephropathy compared to those without nephropathy (p < 0.001), in patients with diabetic retinopathy compared to those without retinopathy (p < 0.001), and in patients with diabetic neuropathy compared to those without neuropathy (p < 0.001). In conclusion, we assert that assessing the PNI may yield additional diagnostic value in regards to the timely determination of diabetic microvascular complications.

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“…Uncontrolled activation of neutrophils leads to the production of reactive oxygen species (ROS) and NETs that play important roles in type-2 diabetes and atherosclerosis. One possibility is the activation of Toll-like receptors (TLRs) from the byproducts on persistent sterile inflammation (16). However, the mechanism of NETosis in the pathogenesis of DKD needs to be further explored.…”

Section: Original Articlementioning

confidence: 99%

Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation

Liu¹,

Ren²,

You-song³

et al. 2022

Ann Transl Med

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Background: We sought to investigate the role of midkine (MK) on neutrophil extracellular trap formation (NETosis) and diabetic kidney disease (DKD) progression. Methods: The expression of MK and NETosis in the renal tissue of DKD patients was examined by immunohistochemistry and immunofluorescence, respectively. Neutrophils extracted from mouse bone marrow by gradient centrifugation were treated with MK for this in-vitro study. A mouse diabetes model was induced by a high-fat diet combined with an intraperitoneal injection of streptozocin (STZ). Antisense oligodeoxynucleotide (ODN) for MK inhibition was administered via tail vein injection. Results: We found that the expression of MK was increased in the kidney tissue of DKD patients. Additionally, a greater number of neutrophils were primed toward NETosis in the kidney tissue of DKD patients, which was manifested by the increased expression of NETosis biomarkers citrullinated histone H3 (H3Cit) and myeloperoxidase (MPO). In vitro, MK treatment concentration-dependently increased neutrophil proliferation (cell counting kit-8). Further, western blot and enzyme-linked immunosorbent assays showed that MK (100 ng/mL) significantly promoted NETosis and the expression of inflammatory factors interleukin (IL)-1 and IL-6 secretion in high-glucose treated neutrophils. In the mouse diabetes model, MK promoted the pathological damage and fibrosis of kidney tissue, as demonstrated by the reversion of the pathological damage and fibrosis by the MK antisense ODN [diabetes mellitus (DM) + MK -ODN] treatment. Additionally, the inhibition of MK reduced the formation of NETs. Conclusions: MK promotes DKD progression by increasing NETosis.

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Role of neutrophils in type 2 diabetes and associated atherosclerosis

Cited by 8 publications

References 50 publications

Utility of neutrophil-to-high-density lipoprotein-cholesterol ratio in patients with coronary artery disease: a narrative review

Utility of neutrophil-to-high-density lipoprotein-cholesterol ratio in patients with coronary artery disease: a narrative review

Association between the Prognostic Nutritional Index and Chronic Microvascular Complications in Patients with Type 2 Diabetes Mellitus

Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation

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