The Dysfunction of NK Cells in Patients with Type 2 Diabetes and Colon Cancer

Piątkiewicz, Paweł; Miłek, Tomasz; Bernat-Karpińska, Małgorzata; Ohams, Monika; Czech, Anna; Ciostek, Piotr

doi:10.1007/s00005-013-0222-5

Cited by 37 publications

(33 citation statements)

References 50 publications

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“…Immunological abnormalities such as abnormal expression of NK cell surface markers and abnormal cytokine production may also be associated with the pathogenesis of DM. In fact, some researchers had reported decreased expression of NKp46 and changed levels of serum cytokines such as IFN‐γ, TNF‐α, TGF‐β, and VEGF in patients with DM . Recently, the relationship between immune response and metabolic diseases such as obesity, type 2 diabetes, and GDM was reported …”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, NK cell cytotoxicity decreased in long‐standing type 1 DM group than that in the non‐DM healthy group . Patients with type 2 diabetes mellitus (DM) and impaired glucose tolerance (IGT) had also significantly lower levels of NK cell activity compared to that of the normal controls in both men and women . These reports prompted us to investigate the expression of pNK cell surface markers and the percentage of cytokine‐producing pNK cells in women with GDM.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Natural Cytotoxicity Receptors on and Intracellular Cytokine Production by NK Cells in Women with Gestational Diabetes Mellitus

Chiba

Fukui

Fuchinoue

et al. 2016

American J Rep Immunol

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Gestational diabetes mellitus (GDM) is characterized by glucose intolerance that is caused by metabolic changes during pregnancy, and is considered a risk factor for the occurrence of DM in future. There are studies that reported changes in the cytokine in women with GDM. The concentration of serum IFN-γ and adiponectin decreased, while serum leptin, IL-6, IL-10, and TNF-α increased in GDM women when compared to that in healthy pregnant women. 16 17 Placenta and adipose tissues from patients with GDM released higher amounts of TNF-α in response to high glucose than that from normal pregnant women.18 Plasma TNF-α were reported to be low during the first and second trimester, but it increased during late pregnancy, and was inversely correlated with the insulin sensitivity. 19, 20 However, the relationship between GDM and the functions of NK cells in pregnant women has not been clarified so far. The purpose of this study was to evaluate the expression of peripheral blood NK (pNK) cell surface markers (CD16, NKp46, and NKp30) and the percentage of cytokine (IFN-γ, TNF-α, TGF-β, and VEGF) producing pNK cells in women with / without GDM at 12 weeks of pregnancy. 2 Materials and Methods Study SubjectsWe designed a prospective study and patients from Hirosaki University Hospital were recruited for this study between July 2014 and March 2015. This study was approved by the local ethics committee, and signed informed consent forms were obtained from all study subjects. Blood samples were collected during routine blood tests for prenatal check-up at 12weeks of gestation.Thirty-four Japanese women (GDM (n=7), non-GDM (n=27)) with singleton pregnancy were included. All GDM patients were diagnosed at 12 to 16 weeks of gestation. Pregnant women with multi-fetal gestations, pre-gestational diabetes, and overt diabetes were excluded, while pregnant women with impaired glucose tolerance before the onset of pregnancy were included in this study. Maternal and neonatal characteristics are shown in Table 1. Two-hour-glucose level of 75-g OGTT in GDM group was significantly higher than that in the non-GDM group.There were no complications reported in the newborn infants (such as macrosomia, shoulder dystocia, and hypoglycemia) in both the GDM and non-GDM groups and there were no pregnant women suffering from PE in both the GDM and non-GDM groups. Screening of GDMAll pregnant women were subjected to a two-step screening method for GDM. This screening method is based on the Guideline for Obstetrical Practice in Japan 2014. 21 Briefly, women who had a random plasma glucose level of ≥95mg/dl at 12 weeks of gestation were subjected to 75-g OGTT after fasting overnight. Diagnosis of GDM was based on the criteria of one or more abnormal values [fasting ≥92mg/dl (5.1mmol/l), such as 1 hour ≥180mg/dl (10.0mmol/l) or 2 hour ≥153mg / dl (8.5mmol/l)] reported for the subjects. Pregnant women, not diagnosed as GDM at 12 weeks of screening, were again subjected to random blood glucose measurement at 3 28 weeks of gestation. Women with random...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression of Natural Cytotoxicity Receptors on and Intracellular Cytokine Production by NK Cells in Women with Gestational Diabetes Mellitus

Chiba

Fukui

Fuchinoue

et al. 2016

American J Rep Immunol

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“…Natural killer (NK) cells participate in innate immune responses and in animal models of T1D, it has been reported that depletion of NK cells prevents the development of T1D . An altered frequency of total number of NK cells has been found in LADA, but not in T2D, patients . Furthermore, it has been reported in children with T1D that NK cells have defects in signalling and function that might contribute to the pathogenesis of T1D .…”

Section: Introductionmentioning

confidence: 99%

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

Singh

Martinell

Luo

et al. 2019

Clinical and Experimental Immunology

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Summary There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age‐matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)‐35 were measured by enzyme‐linked immunosorbent assay (ELISA). The proportion of CD11c+CD123– antigen‐presenting cells (APCs) was lower, while the proportions of CD11c+CD123+ APCs and IL‐35+ tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3–CD56highCD16+ natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL‐35+ regulatory T cells and plasma IL‐35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL‐35+ regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

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“…Other proposed explanations for the increased risk include obesity-related insulin resistance (IR)[11] and cytokine production[12], which may directly influence CRC growth not only through promotion of angiogenesis[13,14], but also by inducing host inflammatory response[13,15] or decreasing natural killer (NK) lymphocyte cytotoxic activity and, thus, the immunological defense against cancer[16]. …”

Section: Introductionmentioning

confidence: 99%

Prognostic value of glycated hemoglobin in colorectal cancer

Ferroni¹,

Formica²,

Della-Morte³

et al. 2016

WJG

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AIMTo investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer (CRC) patients.METHODSPre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile. Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free (PFS) and overall survival (OS) was prospectively evaluated.RESULTSFasting blood glucose, insulin, HOMA-IR and HbA1c (all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage (P = 0.018) was an independent predictor of increased HbA1c levels, which were also higher in patients who had disease progression compared with those who did not (P = 0.05). Elevated HbA1c levels showed a negative prognostic value both in terms of PFS (HR = 1.24) and OS (HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients.CONCLUSIONHbA1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes.

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The Dysfunction of NK Cells in Patients with Type 2 Diabetes and Colon Cancer

Cited by 37 publications

References 50 publications

Expression of Natural Cytotoxicity Receptors on and Intracellular Cytokine Production by NK Cells in Women with Gestational Diabetes Mellitus

Expression of Natural Cytotoxicity Receptors on and Intracellular Cytokine Production by NK Cells in Women with Gestational Diabetes Mellitus

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

Prognostic value of glycated hemoglobin in colorectal cancer

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