YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance

Rathcke, Camilla Noelle; Johansen, Julia S.; Vestergaard, Henrik

doi:10.1007/s00011-005-0010-8

Cited by 166 publications

(151 citation statements)

References 68 publications

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“…YKL-40 protein also accumulates in serum from patients with other diseases such as rheumatoid arthritis 34 or type 2 diabetes. 35 Determining levels of CHI3L1 mRNA from cancer tissue together with its concentration in serum might enhance sensitivity of this promising biomarker. PI3, the gene encoding for elafin, a whey-acidic-protein (WAP) motif protein, is induced >12-fold in VEGF siRNA tumors.…”

Section: Discussionmentioning

confidence: 99%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

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Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti‐angiogenic agents used increasingly in the clinic. However, to be efficient, anti‐VEGF agents need to be associated with classic chemotherapy. Exploring gene regulation in tumor cells during anti‐angiogenesis might help to comprehend the molecular basis of response to treatment. To generate a defined anti‐angiogenic condition in vivo, we transfected human glioma cells with short‐interfering RNAs against VEGF‐A and implanted them on the chick chorio‐allantoic membrane. Gene regulation in avascular tumors was studied using human Affymetrix™ GeneChips. Potentially important genes were further studied in glioma patients. Despite strong VEGF inhibition, we observed recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL‐40, a putative prognosticator for various diseases, including cancer, were strongly up‐regulated in avascular glioma. In glioblastoma patients, these genes showed coregulation and their expression differed significantly from low‐grade glioma. Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004) were significantly correlated with poor survival. Cox regression analysis further confirmed that PI3 and CHI3L1 levels are survival markers independent from patient age and sex. Elafin‐positive tumor cells were only found in glioblastoma, where they were clustered around necrotic areas. PI3/elafin is strongly induced by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results indicate that anti‐angiogenesis in experimental glioma drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and new therapeutic targets. © 2007 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

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“…A substantial body of evidence indicates that YKL-40 participates in processes during the early stages of atherosclerosis, and it seems to be of pathogenic importance in the low-grade inflammation that precedes the development of cardiovascular disease (11)(12)(13)(14). We have previously found significantly elevated levels of YKL-40 in patients with type 2 diabetes and an independent positive correlation with insulin resistance and parameters of the lipid profile (15,16).…”

Section: Diabetes Care 32:323-328 2009mentioning

confidence: 95%

“…However, previous studies either have not shown or have shown only a weak correlation between YKL-40 and hsCRP (r ϭ 0.17, NS, and r ϭ 0.22, P Ͻ 0.0001, respectively) (15,16), and hsCRP levels have not previously been found to influence the predictive value of YKL-40 in terms of overall or cardiovascular mortality (16). Therefore, we would not expect different outcomes if we included hsCRP in the analyses.…”

Section: -Median Levels (Interquartile Range) Of Ykl-40 In the Three mentioning

confidence: 97%

“…Therefore, substantial evidence indicates that YKL-40 participates in monocyte differentiation and macrophage activation as part of the endothelial dysfunction and the processes during early stages of atherosclerosis (11) and seems to be of pathogenic importance in the low-grade inflammation that precedes the development of cardiovascular disease. We have previously found elevated YKL-40 levels in patients with type 2 diabetes (15,16) in whom it correlated with insulin resistance and parameters of the lipid profile, but despite a known macrophage infiltration in adipose tissue, YKL-40 has never been found to be associated with BMI (15).…”

Section: -Median Levels (Interquartile Range) Of Ykl-40 In the Three mentioning

confidence: 98%

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YKL-40, a Marker of Inflammation and Endothelial Dysfunction, Is Elevated in Patients With Type 1 Diabetes and Increases With Levels of Albuminuria

et al. 2009

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OBJECTIVE -The inflammation marker YKL-40 is elevated in patients with type 2 diabetes and is associated with atherosclerosis and increased cardiovascular mortality. In the present study, YKL-40 levels were examined in patients with type 1 diabetes with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease.RESEARCH DESIGN AND METHODS -A total of 149 patients with type 1 diabetes attending Steno Diabetes Center were examined: 58 had normoalbuminuria (urinary albumin excretion rate Ͻ30 mg/24 h), 46 had persistent microalbuminuria (urinary albumin excretion rate 30 -300 mg/24 h), and 45 had persistent macroalbuminuria/diabetic nephropathy (urinary albumin excretion rate Ͼ300 mg/24 h). The control group consisted of 55 healthy individuals. Groups were matched according to sex and duration of diabetes (Ͼ30 years).RESULTS -Median levels [interquartile range] of serum YKL-40 were significantly higher in normoalbuminuria versus control (37 [29 -52] vs. 53 [32-105] ng/ml, P Ͻ 0.01) and were increasing with increasing levels of albuminuria (microalbuminuria 74 [45-160] ng/ml and diabetic nephropathy 117 [68 -215] ng/ml; P Ͻ 0.001 for all comparisons). YKL-40 levels correlated with the urinary albumin-to-creatinine ratio in the total group of participants (r 2 ϭ 0.25, P Ͻ 0.001). Significant but weak intercorrelations of YKL-40 were found with age, diastolic blood pressure, A1C, and serum creatinine. After adjustment for significant covariates, albuminuria was significantly associated with YKL-40 levels (P Ͻ 0.001).CONCLUSIONS -YKL-40 levels are elevated in patients with type 1 diabetes with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. The present study is the first to suggest a role of YKL-40 in the gradually progressing vascular complications in patients with type 1 diabetes.

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“…Thus our results do not provide a rationale for prevention studies using IL-1β antibodies [5] in humans with type 2 diabetes mellitus. On the other hand, type 2 diabetes mellitus is a heterogeneous disease and it cannot be ruled out that an inflammatory background represents a component of the disease process in some patients [27,28].…”

Section: Discussionmentioning

confidence: 99%

Beta cell death in hyperglycaemic Psammomys obesus is not cytokine-mediated

2006

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Aims/hypothesis It has recently been proposed that IL-1β may be responsible for beta cell death in type 2 diabetes mellitus. Major support for this assumption was derived from experiments in the gerbil Psammomys obesus (sand rat), a model for nutritionally induced non-insulin-dependent type 2 diabetes. Using gerbil-specific primers for the analysis of gene expression, we investigated the validity of this hypothesis. Methods Gene expression was analysed by real-time RT-PCR of isolated and laser-microdissected islets and by in situ RT-PCR, both in beta cells and in immune cells, as well as in lymph nodes and spleen. Results We were unable to detect Il-1β and the IL-1β-inducible enzyme inducible nitric oxide synthase (iNos) by in situ RT-PCR, either in the pancreatic beta cells, or in the small number of non-activated immune cells of healthy and diabetic Psammomys obesus after 1 and 3 weeks on a highenergy diet. Very low levels of Il-1β and iNos mRNA were detectable in collagenase-isolated and laser-microdissected islets of normoglycaemic gerbils by real-time RT-PCR without any increase of these mRNAs in islets from diabetic animals. These results were confirmed by electron microscopy with immunogold staining for IL-1β and insulin. Conclusions/interpretation The diabetic syndrome induced in Psammomys obesus by high-energy diet is a classical type 2 diabetes model, which does not show any evidence of an involvement of the proinflammatory cytokine IL-1β or of activated immune cells in its pathogenesis. This is clearly at variance with the situation in type 1 diabetes.

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YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance

Cited by 166 publications

References 68 publications

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

YKL-40, a Marker of Inflammation and Endothelial Dysfunction, Is Elevated in Patients With Type 1 Diabetes and Increases With Levels of Albuminuria

Beta cell death in hyperglycaemic Psammomys obesus is not cytokine-mediated

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