Original Article Received: September 17, 2014 Accepted after revision: January 7, 2015 Published online: February 20, 2015

Gynecol Obstet Invest DOI: 10.1159/000373889

Is There Any Relationship between Plasma Pentraxin 3 Levels and Gestational Diabetes Mellitus? Melahat Yildirim a Serap Aynur Simavli d Aysel Uysal Derbent e Ikbal Kaygusuz b Sema Uysal c   

 

 

a

 

 

Department of Obstetrics and Gynecology, Ankara Ataturk Training and Research Hospital, b Department of Obstetrics and Gynecology, Turgut Özal University Hospital, and c Department of Biochemistry, Ankara Diskapi Training and Research Hospital, Ankara, d Department of Obstetrics and Gynecology, Pamukkale University School of Medicine, Eskisehir, and e Department of Obstetrics and Gynecology, Antalya Training and Research Hospital, Antalya, Turkey  

 

 

 

 

Abstract Background: Pentraxin 3 (PTX3) is a novel vascular inflammatory marker which increases in vascular events such as diabetes mellitus. The aim of this study was to investigate the relationship between serum PTX3 levels and gestational diabetes mellitus (GDM). Methods: This prospective observational study was comprised of 88 pregnant women with singleton pregnancies. The subjects were classified into 3 groups according to their response to a 50-gram glucose challenge test (GCT) and a 100-gram oral glucose tolerance test: control group (n = 28), impaired glucose tolerance group (n = 30), and GDM group (n = 30). Serum PTX3 levels were measured to examine the relationship between GDM and GCT values. Results: Significant differences in PTX3 levels were observed among the 3 groups in the sample (F = 7.598; p = 0.001). The mean PTX3 value was found to be significantly higher in the GDM group (3.17 ± 1.16 ng/ml) than in the control group (2.20 ± 0.83 ng/ml; p = 0.001). A significant positive correlation between PTX3 and GCT values was

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detected (r = 0.289; p = 0.008). Conclusion: Maternal serum PTX3 levels were found to be significantly related to high blood glucose levels. This may be an indicator of vascular pathology in GDM around the time of an oral glucose tolerance test. © 2015 S. Karger AG, Basel

Introduction

Gestational diabetes mellitus (GDM) has been defined as ‘any degree of glucose intolerance with onset or first recognition during pregnancy’ [1]. Although the exact mechanisms responsible for developing GDM are not known, there are several theories as to why GDM occurs [2]. Some of these theories postulate insufficient pancreatic function against an increased insulin resistance, which is triggered primarily by diabetogenic hormones secreted from the placenta during pregnancy, diminished insulin sensitivity, and decreased insulin response. GDM resembles type 2 diabetes in several respects, involving a combination of insufficient insulin secretion from pancreatic beta cells and responsiveness [3]. Studies have shown that vascular disease in diabetes mellitus occurs as Melahat Yildirim Department of Obstetrics and Gynecology Ankara Ataturk Training and Research Hospital TR–06800 Ankara (Turkey) E-Mail melahatyildrim @ yahoo.com

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Key Words Pentraxin 3 · Gestational diabetes mellitus · Vascular inflammation · Pregnancy · Inflammation

Material and Methods This prospective observational study was carried out at the Obstetrics and Gynecology Clinic of Turgut Özal University Hospital between January 2009 and June 2011. The study protocol was approved by the ethics committee of the University and complied with the Helsinki Declaration. A written informed consent was obtained from all participating women. Pregnant women with either GDM (n = 30) or impaired glucose tolerance (IGT; n = 30) were accepted as study groups in our analyses. Control subjects were selected from pregnant women with GCT values in the normal range (n = 28). Patient characteristics [age, gravida, body mass index (BMI)] and historical information were collected and recorded for further analysis. The study participants consisted of 88 pregnant women with singleton pregnancies. Gestational age was determined based on the combination of the last menstrual period and ultrasound findings in the first trimester. BMI was calculated as weight (kg)/height squared (m2) in all cases. All patients at 24– 28 weeks’ gestation received an oral GCT for the purpose of screening GDM. A 50-gram glucose solution was ingested by all pregnant women regardless of their fasting status, and venous blood samples

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Gynecol Obstet Invest DOI: 10.1159/000373889

were collected 1 h later. Venipuncture was performed in the antecubital vein while the women were sitting upright in a chair designed for the purpose of blood sampling. All blood samples were drawn without stasis from the antecubital vein. Women with a 1-hour glucose level ≥135 mg/dl were accepted as having a positive GCT and referred to a diagnostic oral glucose tolerance test (OGTT). The 100-gram OGTT was performed in the morning following overnight fasting. Since our study population consisted of pregnant women, overnight fasting for 10 h was recommended before blood testing. Pregnant women were informed about not eating anything after 10.00 p.m. and admitted to hospital for OGTT at or after 8.00 a.m. Venous blood samples were drawn at baseline (fasting) and 60, 120, and 180 min following ingestion of the standard 100-gram glucose load. OGTT results were evaluated using the Carpenter and Coustan modification of the National Diabetes Data Group (NDDG) criteria [23], which describes positive OGTT as venous plasma glucose concentration ≥95 mg/dl for fasting, ≥180 mg/dl for 1 h, ≥155 mg/dl for 2 h, and ≥140 mg/dl for 3 h. If two or more OGTT parameters were at or above these thresholds, the pregnant woman was classified as having GDM. Patients having one abnormal OGTT parameter or normal OGTT following positive GCT were defined as having IGT. Serum glucose levels were measured using the hexokinase method (COBAS Integra 800, Roche, Germany). Blood glucose values for all women were recorded appropriately. In order to measure the PTX3 levels, venous blood samples of the participants were also collected in the morning following the 10-hour fasting and the day after GCT was performed. Blood samples were immediately centrifuged, kept at –80 ° C until laboratory testing, and thawed immediately just before the analysis. Plasma PTX3 level (ng/ml) was measured by enzyme immunoassay using a quantitative kit (Human PTX3/TSG-14 Immunoassay, DPTX30, R&D Systems, Inc., Minneapolis, Minn., USA). In this assay system, the intra-assay and inter-assay coefficient of variation always stayed under 10%. The minimum detectable concentration rate of PTX3 ranged from 0.007 to 0.116 ng/ml. Patients were stratified into 3 groups based on their response to GCT and OGTT results: (1) control group (normal GCT test results); (2) IGT group (positive GCT and normal OGTT results or one of the aforementioned GDM criteria), and (3) GDM group. The exclusion criteria for the patients were the existence of any type of abnormal pregnancies (polyhydramnios, oligohydramnios, fetal abnormality, preeclampsia, etc.), preexisting systemic or infectious diseases, collagen vascular diseases, inflammatory bowel disease, chronic hypertension, renal diseases, liver diseases, pregestational type 1 and 2 diabetes, polycystic ovarian syndrome, any type of chronic inflammatory conditions, iron deficiency anemia, smoking habit, current steroid usage, and multiple pregnancies. None of the patients were under any treatment with iron, folic acid, vitamin B12 or any drugs known to affect carbohydrate metabolism. The statistical analyses were conducted using IBM SPSS Statistics for Windows, version 21.0 (released 2012, IBM Corp., Armonk, N.Y., USA). The Shapiro-Wilk test was performed to test the normality of distribution of the variables. Continuous variables with normal distribution were presented as mean ± SD. Non-normally distributed variables were presented as median (interquartile range). A power analysis of the study showed that 88 patients were needed to gain 80% power when the alpha error was set at 0.05, the beta error at 0.20 and the effect size at 0.35. One-way  

 

Yildirim/Simavli/Uysal Derbent/ Kaygusuz/Uysal

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a result of endothelial dysfunction [4] and vascular inflammation [5]. Numerous studies have demonstrated a significant relationship between vascular involvement and type 1 and 2 diabetes mellitus [6–9]. Pentraxin 3 (PTX3) is a vascular inflammatory marker which has been the subject of numerous studies related to vascular events in pregnancy and other conditions [10–13]. This marker is one of the endothelium-specific inflammatory cytokines, representing directly the tissue inflammatory response, especially the one involving the vascular bed. Production of PTX3 is considered to be stimulated in many different tissues under the control of the primary inflammatory signal. In addition to vascular endothelial cells, it can be released by various cell types such as macrophages, dendritic cells, etc. as a response to tissue damage and inflammation [14–17]. PTX3 escalates the procoagulant effect of endothelial cells [18] and reduces the endothelial repair by disabling the effect of the fibroblast growth factor. Furthermore, it accelerates the tissue damage and inhibits angiogenesis [19]. Studies have shown that patients with small-vessel vasculitis or inflammatory conditions such as coronary artery disease or myocardial infarction have high plasma levels of PTX3 [20–22]. Further, high PTX3 values are related to vascular dysfunction in patients with type 2 diabetes mellitus [5]. Based on these findings, the aim of this study was to investigate any vascular involvement in GDM by using PTX3, which is accepted as vascular inflammatory marker in the literature. We also evaluate the relationship between serum PTX3 levels and oral glucose challenge test (GCT) values.

Table 1. The patients’ characteristics and serum blood values of each group

Groups

Age, years Gestational age, weeks Gravida Parity Abortions BMI GCT, mg/dl FPG, mg/dl 1-hour PG, mg/dl 2-hour PG, mg/dl 3-hour PG, mg/dl PTX3, ng/ml

p

control (n = 28)

IGT (n = 30)

GDM (n = 30)

27.14 ± 3.18 26.4 ± 0.9 1 (1) 0 (0) 0 (0) 26.20 ± 2.53 109.29 ± 25.15

28.91 ± 5.23 26.3 ± 1.1 1 (1) 0 (0) 0 (0) 27.4 ± 2.86 151.58 ± 11.14 80.06 ± 7.91 149.05 ± 30.71 133.14 ± 27.18 109.46 ± 29.40 2.87 ± 1.15

28.73 ± 4.62 26.2 ± 1.3 3 (1) 1 (1) 0 (1) 29.54 ± 2.04 188.15 ± 30.60 99.50 ± 15.14 209.27 ± 30.98 180.67 ± 31.21 126.80 ± 36.33 3.17 ± 1.16

– – – 2.20 ± 0.83

NS NS NS NS NS 0.001 0.001 0.001 0.001 0.001 0.001 0.001

Values expressed as mean ± SD or median (interquartile range). FPG = Fasting plasma glucose; PG = plasma glucose; NS = not significant.

Pentraxin 3 in Gestational Diabetes Mellitus

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Derived from GCT 150 200

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Fig. 1. Positive correlation between PTX3 and GCT.

ues were distributed as 2.20 ± 0.83, 2.87 ± 1.15, and 3.17 ± 1.16 ng/ml among the 3 groups (control, IGT, and GDM, respectively). Furthermore, the comparison of PTX3 values revealed significant differences across the 3 groups (F = 7.598; p = 0.001). In pairwise comparison, the mean PTX3 values between the control group and the GDM group were found to be statistically significant (p = 0.001), while the same analysis between the control group and the IGT group revealed a statistically insignificant result (p = 0.058). In addition, no significant differences Gynecol Obstet Invest DOI: 10.1159/000373889

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The study is comprised of 88 pregnant women with singleton pregnancies (30 women in the GDM group, 30 women in the IGT group, and 28 women in the control group). The mean age was found to be very similar in all 3 groups (28.73 ± 4.62 years for the GDM group, 28.91 ± 5.23 years for the IGT group, 27.14 ± 3.18 years for the control group). The differences in ages among the 3 groups were not statistically significant. Table 1 presents the demographic characteristics and serum glucose levels as well as PTX3 levels of each group. The fasting blood glucose level and the 50-gram GCT level were both significantly higher in the GDM group than in the control and IGT groups (p < 0.001 for both). The BMI measure was higher in diabetic patients compared to patients in the IGT and control groups (p < 0.001). GCT values were measured as 109.29 ± 25.15 mg/dl for the control group, 151.58 ± 11.14 mg/dl for the IGT group, and 188.15 ± 30.60 mg/dl for the GDM group. In the study, PTX3 val-

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Derived from PTX3

Results

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PTX3

(parametric) ANOVA with Bonferroni adjustment was performed to compare control, IGT, and GDM groups. The ANOVA test was used to determine any correlation between and within the groups. Univariate differences between continuous and categorical variables were assessed respectively. The distribution of PTX3 levels among the 3 groups were calculated and recorded. An association between PTX3 and GCT was shown using the Pearson correlation test. A p value

Is There Any Relationship between Plasma Pentraxin 3 Levels and Gestational Diabetes Mellitus?

Pentraxin 3 (PTX3) is a novel vascular inflammatory marker which increases in vascular events such as diabetes mellitus. The aim of this study was to ...
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