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

Weijing Zhao,Yajuan Huang,Weiping Jia,Fang Liu,Jiemin Pan,Minfang Tao,Huaping Li,Dongmei Li

doi:10.1371/journal.pone.0147277

Weijing Zhao, Yajuan Huang + Show 6 more

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https://doi.org/10.1371/journal.pone.0147277

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Abstract

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.

Highlights

Gestational diabetes mellitus(GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy
It may be a helpful biomarker to identify the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women
A GDM diagnosis was based on the following criteria established by the American Diabetes Association (ADA) in 2013[24]: fasting plasma glucose (FPG)5.1mmol/L; and/or 60 minutes plasma glucose levels10.0mmol/L; and/or 120 minutes plasma glucose levels8.5mmol/L

Summary

Introduction

Gestational diabetes mellitus(GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. CysC, an endogenous inhibitor of cathepsin proteases, is produced by human nucleated cells, freely filtered at the glomerulus and reabsorbed in the proximal renal tubular cells. It is considered a more sensitive measure for estimating the glomerular filtration rate (GFR)than serum creatinine (Cr)[4], and is superior to Cr as a marker of kidney function[5,6,7]and is the risk factor of cardiovascular disease(CVD)[8,9]and diabetes retinopathy as well[10]

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