Does serum cystatin C level reflect insulin resistance in patients with type 1 diabetes?

Uruska, Aleksandra; Araszkiewicz, Aleksandra; Zozulińska−Ziółkiewicz, Dorota; Wegner, Małgorzata; Grzelka, Agata; Wierusz‐Wysocka, Bogna

doi:10.1016/j.clinbiochem.2014.06.014

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…It has been shown that Cys C is an ubiquitously expressed protein and its levels are elevated in renal dysfunction [14], cardiovascular diseases [15], diabetes [9,16], obesity [8] and hypertension [17]. To evaluate which tissues are the main resources for the elevated Cys C in diabetes and obesity, we analyzed the expression profiles of Cys C in several tissues of the ob/ob mice and their lean control animals.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Cys C was found to be associated with 3‐year incident diabetes but only in people with central adiposity or insulin resistance [8]. Most recently, a clinic survey showed that higher level of serum Cys C is related to decreased insulin sensitivity in patients with type 1 diabetes [9]. However, up to date, no evidence regarding whether Cys C directly promotes insulin resistance or dysregulated glucose metabolism in type 2 diabetes was reported.…”

Section: Introductionmentioning

confidence: 99%

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Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes

Yao

Wang

et al. 2015

FEBS Letters

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a b s t r a c tIt has been reported that cystatin c (Cys C) closely correlates with metabolic disorders such as obesity and diabetes. However, it is still unknown whether Cys C plays a role for these disorders. Our results showed that the insulin signal transduction was largely impaired by Cys C in hepatocytes. In myotubes, however, the insulin signal transduction was not affected. Following experiments revealed that Cys C could induce endoplasmic reticulum stress (ER stress) in hepatocytes, whereas Cys C had no such an effect in myotubes. The alleviation of ER stress by 4-Phenyl butyric acid (4-PBA) restored the impaired insulin signal transduction in Cys C-treated hepatocytes. These results provided direct evidence that, by inducing ER stress, Cys C impairs insulin signal transduction in hepatocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes

Yao

Wang

et al. 2015

FEBS Letters

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“…The insulin signaling cascades in kidney mainly includes phosphoinoside-3-kinase (PI3K), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), glucose transporter 4 (GLUT4), and adenosine monophosphate activated protein kinase (AMPK). Clinically, a higher level of serum cystatin C was associated with decreased insulin sensitivity in type 1 diabetic patients ( Uruska et al, 2014 ). Although whether the level of cystatin C can accurately reflect insulin resistance remains to be verified, the role of insulin signaling pathway which was found in pathway-based association analyses cannot be ignored as the genetic background of cystatin C.…”

Section: Discussionmentioning

confidence: 99%

Pathway Association Studies Reveal Gene Loci and Pathway Networks that Associated With Plasma Cystatin C Levels

Jiao

Zhang

et al. 2021

Front. Genet.

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As a marker for glomerular filtration, plasma cystatin C level is used to evaluate kidney function. To decipher genetic factors that control the plasma cystatin C level, we performed genome-wide association and pathway association studies using United Kingdom Biobank data. One hundred fifteen loci yielded p values less than 1 × 10−100, three genes (clusters) showed the most significant associations, including the CST8-CST9 cluster on chromosome 20, the SH2B3-ATXN2 gene region on chromosome 12, and the SHROOM3-CCDC158 gene region on chromosome 4. In pathway association studies, forty significant pathways had FDR (false discovery rate) and or FWER (family-wise error rate) ≤ 0.001: spermatogenesis, leukocyte trans-endothelial migration, cell adhesion, glycoprotein, membrane lipid, steroid metabolic process, and insulin signaling pathways were among the most significant pathways that associated with the plasma cystatin C levels. We also performed Genome-wide association studies for eGFR, top associated genes were largely overlapped with those for cystatin C.

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“…There has been some evidences to support the association between insulin resistance and serum CysC level. Previous research has shown that a higher level of serum CysC was related to decreased insulin sensitivity in 71 Caucasian patients with type 1 diabetes mellitus[ 29 ]. Additionally, some data suggested the dependence between CysC and insulin resistance in T2DM patients[ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus

Zhao

Pan

et al. 2016

PLoS ONE

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AimsSerum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women.MethodsThis cross-sectional study consisted of 400 pregnant women including111 with GDM and 289 with normal glucose tolerance at 24–28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).ResultsSerum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8–1.8) vs 0.7(0.6–1.0), P<0.01). The Spearman’s correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977–40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95mg/L.ConclusionsSerum CysC is significantly and independently associated with insulin resistance and GDM. It may be a helpful biomarker to identify the risk of GDM in Chinese pregnant women.

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Does serum cystatin C level reflect insulin resistance in patients with type 1 diabetes?

Cited by 14 publications

References 29 publications

Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes

Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes

Pathway Association Studies Reveal Gene Loci and Pathway Networks that Associated With Plasma Cystatin C Levels

Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus

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