Next Article in Journal
Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia
Next Article in Special Issue
The Influence of Gestational Diabetes Mellitus upon the Selected Parameters of the Maternal and Fetal System of Insulin-Like Growth Factors (IGF-1, IGF-2, IGFBP1-3)—A Review and a Clinical Study
Previous Article in Journal
Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19
Previous Article in Special Issue
Pre-Pregnancy Obesity, Excessive Gestational Weight Gain, and the Risk of Pregnancy-Induced Hypertension and Gestational Diabetes Mellitus
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JCM
Volume 9
Issue 8
10.3390/jcm9082587
jcm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study

by
Tomasz Gęca
*,
Maciej Kwiatek
,
Arkadiusz Krzyżanowski
and
Anna Kwaśniewska
Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(8), 2587; https://doi.org/10.3390/jcm9082587
Submission received: 15 May 2020 / Revised: 17 July 2020 / Accepted: 30 July 2020 / Published: 10 August 2020
(This article belongs to the Special Issue Risks Associated with Obesity in Pregnancy, for the Mother and Baby)
Browse Figures
Versions Notes

Abstract

:
Background: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnant women, defined as any degree of glucose intolerance with onset or first detected during pregnancy. Explanation of its pathogenesis is extremely important due to the possibility of preventing serious maternal and fetal complications. The aim of the study was to evaluate the concentrations of two molecules: C1q/tumor necrosis factor-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF) which may possibly participate in GDM development. To our knowledge, this is the first study in pregnant women with GDM evaluating CTRP-3 level. Methods: Serum CTRP-3 and PEDF concentration and clinical characteristics were detected in 172 pregnant women. These women were divided into two groups: normal glucose tolerance group (NGT, n = 54) and gestational diabetes mellitus group (GDM, n = 118). This second group was further divided into two subgroups depending on the treatment used: GDM 1—diet only (n = 75) and GDM 2—insulin treatment (n = 43). Results: Our study did not reveal any statistically significant difference between the concentration of PEDF in the control and GDM group. In our study there was a significantly higher concentration of CTRP-3 evaluated in the peripheral blood serum in patients with gestational diabetes (GDM) compared to those in the control group (8.84 vs. 4.79 ng/mL). Significantly higher values of CTRP-3 were observed in both the diet-treated subgroup and the group with insulin therapy when compared to control group (8.40 and 10.96, respectively vs. 4.79 ng/mL). Conclusion: PEDF concentration does not change in GDM, whereas an increased level of CTRP-3 may point to the key role of this adipokine in the development of GDM.

1. Introduction

Gestational diabetes mellitus (GDM) is a special form of diabetes in pregnant women defined as any degree of glucose intolerance with onset or first recognition during pregnancy [1]. GDM affects up to 15% of pregnant women worldwide [2]. It is a particularly important public health issue that is associated with serious consequences for both mother (gestational hypertension, preeclampsia, delivery trauma) and offspring (macrosomia, preterm birth, shoulder dystocia, congenital malformations) [3,4,5]. GDM is also associated with long-term consequences such as metabolic syndrome, cardiovascular disease and type 2 diabetes in the offspring [6]. Most women with GDM revert to normal glucose metabolism during puerperium; however, they are at higher risk of developing type 2 diabetes later in life [7].
The precise mechanisms underlying this form of diabetes in pregnancy remain unclear, but pancreatic β-cell insufficiency in compensating for pregnancy-induced insulin resistance is considered to be important [8]. Explanation of GDM pathogenesis is important due to the possibility of preventing maternal and fetal complications. Two molecules, C1q/tumor necrosis factor-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF), may possibly participate in GDM development due to the fact that underlying mechanisms of GDM are, in general, similar to the mechanisms responsible for metabolic disorders such as type 2 diabetes mellitus or obesity.
The complement C1q tumor necrosis factor related protein (CTRP) superfamily is a newly found cluster of adipokines with a common structure composed of collagenous and globular C1q-like domains. CTRP-3 was first discovered in 2001 in C3H10T1/2 mouse mesenchymal stem cells treated to induce chondrogenic differentiation and was originally named CORS26 (Collagenous repeat-containing sequence 26 kDa protein) due to its specific structure—23 Gly-X-Y repeats in the N-terminal collagen domain [9]. After Wong et al. identified CORS26 as a member of CTRP family with highly conserved adiponectin paralogs it was renamed CTRP-3. N-terminal Collagenous repeats (Gly-X-Y), and a highly conserved C-terminal globular domain, place CTRP3 within the C1q TNF Superfamily [10]. It shares sequence homology with adiponectin and is highly conserved with almost 96% identity between human and mouse proteins [11]. In addition, two splice variants of CTRP-3 were identified: CTRP-3A and CTRP-3B. Unlike CTRP-3A, CTRP-3B contains a highly conserved N-linked glycosylation site. CTRP-3B is the longer splice variant and encodes an extra 73 N-terminal amino acids due to the retention of intron 1. Both splice variants of CTRP-3 are secreted proteins, but their functional significance remains unknown [12]. Recent studies have suggested that this paralog of adiponectin may play an important role in the regulation of glucose metabolism and thus in GDM pathogenesis [12]. This novel adipokine is characterized by multiple metabolic effects such as lowering glucose levels, inhibiting gluco-neogenesis and increasing angiogenesis and anti-inflammation [12,13]. It is also known as a cartonectin, and cartducin, both due to the detection of CTRP-3 expression in developing cartilage [14].
Pigment epithelium-derived factor (PEDF), a multifunctional protein, consisting of 418 amino acids, is associated with insulin resistance and metabolic syndrome. PEDF induces insulin resistance in human adipocytes and skeletal muscle cells [15,16]. The combination of increased insulin resistance and insufficient insulin response during pregnancy seems to be the main pathophysiological mechanism responsible for GDM development. PEDF is a 50 kDa secreted glycoprotein that belongs to the non-inhibitory serpin group [17]. The gene encoding PEDF, Serpinf1, is located on chromosome 17p13 and is widely expressed in many tissues [18]. The highest expression levels in humans are found in the liver and adipose tissue [19]. It was first purified from a conditioned media of retinal epithelial cells and identified as a neurotrophic factor with potent neuronal differentiative activity (ability to convert retinoblastoma tumor cells into differentiated non-proliferative neurons) [20]. It is assumed that PEDF functions via receptors: ATGL (adipose triglyceride lipase) and laminin-R. Patatin-like phospholipase domain containing protein-2 (PNPLA2), also known as ATGL, was first identified in 2006 by Notari et al. [21]. The second known receptor of PEDF, laminin-R, was described three years later and is associated with a number of processes such as cell proliferation, differentiation, adhesion and migration [22]. The multiplicity of PEDF functions led the researchers to assume that there were more than two receptors for PEDF and several putative receptors were suggested as taking part in the PEDF acting mechanism that include lipoprotein receptor-related protein 5 (LPR5) and cell surface F1F0-ATP synthase, which are involved in PEDF anti-angiogenic activity [23]. The regulatory effect of PEDF on lipid and carbohydrate metabolism is mediated by ATGL which activates adipose lipolysis. This mechanism may contribute to insulin resistance in obese subjects [24]. Borg et al. noted that ATGL-deficient mice do not develop PEDF-induced insulin resistance [24].
However, despite such a large role that these two proteins play in carbohydrate metabolism, no previous reports have measured circulating CTRP-3 levels in GDM and only one evaluates PEDF as a potential early detection marker for predicting development of GDM to diabetes mellitus [25]. We have therefore decided to measure CTRP-3 and PEDF in pregnant women with GDM in comparison to normoglycemic women, and find correlations.

2. Experimental Section

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee of Medical University of Lublin in Lublin. Poland) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical Approval Code is 0254/120/2016.
This article does not contain any studies with animals performed by any of the authors.
A total of 200 women in the third trimester of pregnancy were recruited between March 2016 and December 2018 from the Department of Obstetrics and Pathology of Pregnancy of the Independent Public Teaching Hospital No 1 in Lublin. Of the 200 pregnancies, 28 were excluded because of inadequate data (no BMI counted before pregnancy, incomplete oral glucose tolerance test 75 g results), co-existing diseases (pregestational diabetes, hypertension, preeclampsia, thyroid gland diseases, chronic renal disease, and collagenosis), multiple pregnancies, or fetal chromosomal abnormalities. In total, 172 pregnant women were included in the study. These women were divided into two groups: normal glucose tolerance group (NGT, n = 54) and gestational diabetes mellitus group (GDM, n = 118). This second group was further divided into two subgroups depending on the treatment used: GDM 1—diet only (n = 75) and GDM 2—insulin treatment (n = 43). The diagnosis of GDM was based on the WHO criteria [1]. The present study was conducted in accordance with the Declaration of Helsinki of the World Medical Association and was approved by the Ethics Committee of the Medical University of Lublin in Lublin, Poland (Nr 0254/120/2016). A written informed consent was obtained from all participants. The basic workflow of this study is presented in Figure 1.
The database of clinical background characteristics included gravidity, parity, maternal age, pre-pregnancy body mass index (BMI), gestational weight gain, OGTT 75 g results, gestational age at delivery, delivery mode including vaginal delivery or cesarean section, and newborn parameters including sex, birth weight, and APGAR score (1 and 5 min after birth). Pre-pregnancy body weight was determined based on self-reporting at the first obstetrical visit. Gestational age was determined based on the last menstrual period or the measurement of crown-rump length assessed by ultrasound in early pregnancy in cases of unknown date of last menstrual period or irregular menstrual period. The women with GDM received guidance regarding self-monitoring of blood glucose levels four to six times a day from a licensed nurse. Dietary counseling was provided for each woman with GDM. Height and body weight were measured by standardized methods in all subjects. The body mass index (BMI) formula was computed as weight in kilograms divided by height in meters squared. The homeostasis model assessment of insulin resistance (HOMA-IR) = fasting insulin (mU/L) * fasting plasma glucose (mmol/L)/22.5.
Blood samples were collected in the morning (7–9 a.m.) after an overnight fasting (≥8 h). Plasma samples were obtained by centrifugation at 2000× g for 10 min at 4 °C and were kept at −80 °C before analyses. Plasma glucose levels were measured using the spectrophotometric method (Glucose Assay Kit (Cat No. SUP6016, Empire Genomics with the use of Epoch Microplate Spectrophotometer, BioTek Instruments (Winooski, VT, USA), fasting insulin was measured using Insulin ELISA (Cat No. EIA-2935, DRG Instruments GmbH, Marburg, Germany). The concentration of Human pigment epithelium-derived factor (PEDF) in samples was determined using ELISA kits purchased from Sunred Biological Technology Co., Ltd. (Cat. No. 201-12-1635, Shanghai, China). Concentrations of human CTRP3 were measured with a commercial ELISA kit (Aviscera Bioscience, Cat. No.SK00082-07, Santa Clara, CA, USA). The assays were performed according to the manufacturer’s instructions.

Statistical Methods

The statistical analysis was performed using statistical software (Statistica 13). The correlations of selected biomarkers and continuous clinical variables (measured by means of Spearman non-parametric test or Pearson parametric test depending on the distribution of data) were analysed within all the subgroups. Particular groups were assessed on the basis of the distribution of the above-mentioned variables (Shapiro-Wilk test). Since all tested variables, in at least one of the compared subgroup, showed non-normal distribution, the results were presented as medians. In order to compare the data distribution of continuous variables with a non-normal distribution, a non-parametric U-Mann Whitney (comparison of 2 groups) or ANOVA Kruskal-Wallis (comparison of more than 2 groups) tests was used. The distribution of variables categorized in relevant subgroups was compared by means of Chi square test. P values < 0.05 were considered statistically significant.

3. Results

3.1. The Characteristics and Comparison of Selected Clinical and Laboratory Variables Depending on the Occurrence of Diabetes during Pregnancy and the Implemented Treatment (A Diet or an Insulin Therapy)

The median age of the control group was 29 years. The median age in the GDM group was 32 years, of which GDM1 and GDM2 were 31 and 32 years, respectively. The study group did not differ in terms of basic factors such as: age, number of pregnancies, number of labours, type of delivery, child’s sex, weight of a new-born, height and weight of mother (both before pregnancy and currently). The groups included in the study did not display any significant differences as to PEDF and insulin concentrations. However, in the case of BMI (assessed before pregnancy), higher values (>24.99: overweight) were significantly more often observed in women with GDM, regardless of the treatment (Control (11.11%) vs. GDM1 (34.67%, p = 0.0055), GDM2 (44.19%, p = 0.0005) and GDM1 + 2 (38.14%, p = 0.0014)). In the GDM group compared to the control group, median BMI (assessed before pregnancy) was significantly higher (23.44 vs. 23.28; p = 0.0341). Interestingly, median BMI was also significantly higher in GDM2 subgroup compared to both GDM1 and control (24.22 vs. 23.23 and 23.28, respectively; p = 0.0164). A substantially higher concentration of CTRP3 in peripheral blood plasma was noted in the patients with diagnosed gestational diabetes mellitus (GDM) as compared to the respondents from the control group (8.84 vs. 4.79 ng/mL; p = 0.0265; Figure 2). Considerably higher values of this marker (compared to the control group) were observed in both the diet-treated subgroup (GDM 1: 8.40 vs. 4.79 ng/mL) and the insulin therapy group (GDM 2: 10.96 vs. 4.79 ng/mL) (p = 0.0178). Detailed data including the differences between the study groups in terms of selected clinical and laboratory parameters are presented in Table 1 and Table 2.

3.2. Correlations between the Selected Clinical and Laboratory Variables as Well as PEDF Marker and CTRP3 in the Groups of: Healthy Respondents, Patients with Gestational Diabetes Mellitus (GDM), Gestational Diabetes Mellitus Treated by Means of Diet (GDM1) and by Means of Insulin Therapy (GDM2)

A weak, negative correlation between PEDF concentration and body weight (initial weight) was noted in GDM group (rho = −0.229, p = 0.0438). On the other hand PEDF concentration correlated strongly and positively with APGAR 2 (rho = 0.825, p = 0.0117). In fact, this correlation refer to GDM2 group because APGAR 2 data was not available for the GDM1 group. Moreover, PEDF concentration was also weakly and negatively correlated with BMI indicator (assessed before pregnancy) in GDM2 group (rho = −0.351, p = 0.0210). In the control group moderate, negative correlation between PEDF concentration and age was found (rho = −0.412, p = 0.0020). Interestingly only in the case of healthy women (control group), a trend to the statistically significant result (weak positive correlation) between PEDF concentration and the increase of weight during pregnancy was noted (rho = 0.290, p = 0.0504). Both in GDM and GDM2 groups there was weak, positive correlation between CTRP3 concentration and insulin (rho = −0.208, p = 0.0243; rho = 0.333, p = 0.0293, respectively). However, in both above mentioned groups we found weak, negative correlation between CTRP3 concentration and gestational age (rho = −0.254, p = 0.0070; rho = −0.382, p = 0.0126, respectively). On the other hand in GDM1 group weak, negative correlation between CTRP3 concentration and current weight (rho = −0.256, p = 0.0341) as well as increase of weight during pregnancy (rho = −0.352, p = 0.0326) was found. Interestingly, in none of the studied groups, CTRP3 did not correlate with baseline weight or BMI. Detailed data referring to the correlations between the selected clinical and laboratory variables as well as PEDF markers and CTRP3 in the groups of healthy respondents, patients with gestational diabetes mellitus (GDM 1 + 2), gestational diabetes mellitus treated by means of diet (GDM1) and by means of insulin therapy (GDM2) are presented in Table 3 and Table 4. PEDF concentration does not change in GDM but it tends to grow predominantly in the case of long-term diabetes and its complications. In addition, the increased level of CTRP3 in GDM may be indicative of this component’s role in the development of GDM.

4. Discussion

GDM is a condition of carbohydrate intolerance with onset or first recognition in pregnancy and the most common metabolic disorder in pregnant patients [26]. Studies have shown that the incidence of gestational diabetes is increasing, which may result from postponing procreation plans for later years and the growing epidemic of obesity, diabetes and pre-diabetes states in the general population [27,28,29]. Variation in prevalence rates of GDM could be related to different diagnostic criteria used for screening and diversity of the populations being studied. The prevalence ranges from less than 2% in Sweden to 20.6% in United Arab Emirates [30]. GDM is a worldwide metabolic disorder that has negative maternal and neonatal effects with long-term consequences [31,32]. It is associated with adverse maternal health outcomes such as gestational hypertension, pre-eclampsia, caesarean section, and neonatal outcomes including hyperinsulinemia, macrosomia (usually defined as a neonate weighing over 4 kg), shoulder dystocia, and hypoglycemia. GDM is also a risk factor for future maternal obesity, type 2 diabetes and cardiovascular disease [33,34]. In most developed countries universal screening for GDM is preferred using fasting glucose and OGTT for diagnosis [35]. In a recent meta-analysis it was demonstrated that women with GDM had 7.43 times the likelihood of developing T2DM as pregnant women without GDM [7]. In normal pregnancy, insulin resistance increases in the second trimester, but most women remain euglycemic due to beta cell compensation and increased insulin secretion. GDM develops when beta cell compensation is inadequate for the hepatic glucose production and the level of insulin resistance [36]. Some authors have even demonstrated a reduction of pancreatic β-cell function by 67% in women with GDM compared with normal glucose tolerance controls [37].

4.1. CTRP-3

C1q/tumor necrosis factor related protein-3 (CTRP 3) is a novel adipokine belonging to the CTRP family and mainly secreted by mesenteric adipose tissue in humans [38]. Currently it is considered to be a crucial hormone involved in glucose and lipid metabolism [39]. It activates adenosine monophosphate-activated protein kinase (AMPK) and improves insulin signaling plus insulin sensitivity [12]. Furthermore, CTRP3 reduces secretion of inflammatory cytokines from 3T3-L1 adipocytes [40]. CTRP3 expression can decline in insulin resistance, where treatment with glucagon-like peptide-1 (GLP-1) receptor agonist enhances its expression and improves insulin sensitivity [41]. The association of circulating CTRP-3 with diabetes mellitus has been reported [39,42]. However, there are conflicting results considering concentration of CTRP-3 in diabetes mellitus. Qu et al. reported decreased circulating levels of CTRP-3 in patients with type 2 diabetes, while others showed increased levels of CTRP-3 in subjects with type 2 diabetes [42,43]. Ban et al. examined circulating CTRP-3 levels before and two hours after a glucose load and observed that in type 2 diabetic patients CTRP3 levels decreased from about 150 to 50 ng/ml in response to oral glucose load [39]. In this study glucose and insulin concentrations were significantly higher after the two hours OGTT, so both glucose and insulin could account for the reduction in serum CTRP-3 concentrations. Unfortunately, in the analyzed literature, we did not find any research on the concentration of CTRP-3 in GDM.
Choi et al. reported elevated CTRP-3 concentrations in prediabetes and type 2 diabetes compared with a normal glucose tolerance group [43]. In our study there was also a significantly higher concentration of CTRP-3 evaluated in the peripheral blood serum in patients with GDM compared to those in the control group. Higher concentration of CTRP-3 was observed in both subgroups (GDM1 and GDM2). Elevated values of this marker may suggest that these women are at increased risk of developing type 2 diabetes in a feature life. Similarity of the results of CTRP3 concentrations obtained in patients with GDM, prediabetic states and diabetes confirm that GDM is a real harbinger of future diabetes mellitus development. In a recent Chinese study, plasma CTRP-3 concentrations were significantly lower in subjects with pre-diabetes and type 2 diabetes mellitus compared with a normal glucose tolerance group [44]. A multiple linear regression analysis showed the plasma CTRP-3 levels were independently associated with homeostasis model assessment for insulin resistance (HOMA-IR). Further multiple logistical analyses indicated that plasma CTRP-3 concentrations were significantly correlated with prediabetes states and type 2 diabetes mellitus after adjusting for potential confounders. These results may indicate that CTRP-3 is an independent and strong predictor for prediabetes and diabetes [44].
Recent clinical studies demonstrate that the concentrations of CTRP-3 are lower in obese patients [45]. In the current study we also found weak, negative correlation between CTRP-3 concentration and current weight as well as increase of weight during pregnancy in women with GDM1. Interesting results were provided by the Wagner et al. study. They reported that CTRP-3 level is elevated in obese male but reduced in obese female subjects [46]. This gender specific regulation and function of CTRP3 requires further research. In the study by Moradi et al., CTRP3 demonstrated a negative correlation with HOMA-IR in type 2 diabetes cases [47]. It could be caused by the effect of insulin resistance on the expression of this adipokine in adipose tissue. Our research has not confirmed this relationship which may indicate the presence of other mechanisms regulating CTRP-3 levels during pregnancy.

4.2. PEDF

Pigment epithelium-derived factor (PEDF) is a 50-kDa glycoprotein belonging to the serine protease inhibitor (serpin) supergene family, located on chromosome 17p13.1 [48]. It is known as a pleiotropic protein which was first extracted from the medium of human fetal retinal pigment epithelium [49]. Mainly liver and adipose tissue are responsible for the production of circulating PEDF; however, it is expressed in most tissues examined [15]. Li et al. showed that serum PEDF, measured at 24–32 weeks of gestation, was elevated in pregnant women with GDM compared to those without GDM, which is probably an early detection marker for predicting development of GDM to type 2 diabetes mellitus [25]. Furthermore, univariate correlation data in pregnant women demonstrated that serum PEDF level was positively related with fasting glucose and HOMA-IR [25]. PEDF is not only associated with insulin sensitivity and diabetes mellitus but also with its complications [16,50,51].
PEDF has been found to be elevated in type 2 diabetes, polycystic ovarian syndrome and metabolic syndrome but the role of PEDF in diabetes is not well understood and needs to be further researched [52,53,54,55]. Some authors postulate that dysregulation of the PEDF-ATGL interaction may be associated with the elevation of PEDF level in serum. ATGL is crucial for lipid homeostasis lipase and putative PEDF receptor at the same time [56,57]. Our study did not reveal any statistically significant difference between the concentration of PEDF in the control and GDM groups as well as between subgroups with GDM1 and GDM2. The result of this study can be explained by the fact that PEDF concentration increases in more advanced stages of diabetes when typical diabetic complications develop, but not in GDM cases [50,51].
In the literature it is noted that insulin resistance and higher concentration of PEDF depend on obesity [52,58,59]. Nowadays, it is obvious that adipose tissue is not only a storage site for triglycerides but also an important endocrine organ [60].
Adipocytes release adipokines and contribute to a chronic low-grade inflammation state. PEDF expression in adipose tissue positively correlates with obesity and insulin resistance in mice. It is highly probable that the combination of obesity with hyperinsulinemia lead to increased PEDF serum concentration [61]. The results of human studies are consistent with the above mentioned report and describe a significant correlation between PEDF and obesity [55,62].
The mechanisms of how PEDF induces insulin resistance are not well understood. One of the factors contributing to insulin resistance is inflammation. PEDF is characterized by proinflammatory actions in several cell types [63]. In our study only a weak correlation between PEDF and a body weight (initial weight) was noted in GDM group. PEDF concentration was also weakly and negatively correlated with BMI (assessed before pregnancy). This may indicate that in GDM patients weight and weight gain do not influence PEDF concentrations as they do in chronic diabetes.
There were some limitations to this study. First, it was performed using only one sample of blood in the third trimester. Secondly, because this study included only European subjects, our results may not apply to other populations.

5. Conclusions

In conclusion, CTRP-3 concentrations were significantly higher in patients with GDM than the normal glucose tolerance group, whereas PEDF levels were not different. Due to the fact that CTRP-3 concentrations are elevated in GDM, further research is needed on the use of this parameter in the diagnosis of GDM.

Author Contributions

T.G. and M.K. were responsible for the study conceptualization. project organization, manuscript writing and editing, and interpretation of data. A.K. (Arkadiusz Krzyżanowski) was responsible for data acquisition and statistical analysis. A.K. (Anna Kwaśniewska) was responsible for supervising this work. All authors have read and approved the final manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. World Health Organization. Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy; World Health Organization: Geneva, Switzerland, 2013; pp. 1–62. [Google Scholar]
  2. Guariguata, L.; Linnenkamp, U.; Beagley, J.; Whiting, D.R.; Cho, N.H. Global estimates of the prevalence of hyperglycaemia in pregnancy. Diabetes Res. Clin. Pract. 2014, 103, 176–185. [Google Scholar] [CrossRef] [PubMed]
  3. Wu, L.; Han, L.; Zhan, Y.; Cui, L.; Chen, W.; Ma, L.; Lv, J.; Pan, R.; Zhao, D.; Xiao, Z. Prevalence of gestational diabetes mellitus and associated risk factors in pregnant Chinese women: A cross-sectional study in Huangdao. Qingdao. China. Asia Pac. J. Clin. Nutr. 2018, 27, 383–388. [Google Scholar]
  4. Catalano, P.M.; McIntyre, H.D.; Cruickshank, J.K.; McCance, D.R.; Dyer, A.R.; Metzger, B.E.; Lowe, L.P.; Trimble, E.R.; Coustan, D.R.; Hadden, D.R. The hyperglycemia and adverse pregnancy outcome study: Associations of GDM and obesity with pregnancy outcomes. Diabetes Care 2012, 35, 780–786. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Ovesen, P.G.; Jensen, D.M.; Damm, P.; Rasmussen, S.; Kesmodel, U.S. Maternal and neonatal outcomes in pregnancies complicated by gestational diabetes. A nation-wide study. J. Matern. Fetal. Neonatal Med. 2015, 28, 1720–1724. [Google Scholar] [CrossRef] [PubMed]
  6. Barker, D.J.P. The origins of the developmental origins theory. J. Intern. Med. 2007, 261, 412–417. [Google Scholar] [CrossRef] [PubMed]
  7. Bellamy, L.; Casas, J.P.; Hingorani, A.D.; Williams, D. Type 2 diabetes mellitus after gestational diabetes: A systematic review and meta-analysis. Lancet 2009, 373, 1773–1779. [Google Scholar] [CrossRef]
  8. Buchanan, T.A.; Xiang, A.H. Gestational diabetes mellitus. J. Clin. Investig. 2005, 115, 485–491. [Google Scholar] [CrossRef] [Green Version]
  9. Wong, G.W.; Krawczyk, S.A.; Kitidis-Mitrokostas, C.; Revett, T.; Gimeno, R.; Lodish, H.F. Molecular, biochemical and functional characterizations of C1q/TNF family members: Adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem. J. 2008, 416, 161–177. [Google Scholar] [CrossRef] [Green Version]
  10. Wong, G.W.; Wang, J.; Hug, C.; Tsao, T.S.; Lodish, H.F. A family of Acrp30/adiponectin structural and functional paralogs. Proc. Natl. Acad. Sci. USA 2004, 101, 10302–10307. [Google Scholar] [CrossRef] [Green Version]
  11. Li, W.; Cowley, A.; Uludag, M.; Gur, T.; McWilliam, H.; Squizzato, S.; Park, Y.M.; Buso, N.; Lopez, R. The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic Acids Res. 2015, 43, 580–584. [Google Scholar] [CrossRef] [Green Version]
  12. Peterson, J.M.; Wei, Z.; Wong, G.W. C1q/TNF-related protein-3 (CTRP3) a novel adipokine that regulates hepatic glucose output. J. Biol. Chem. 2010, 285, 39691–39701. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Wang, S.; Ling, Y.; Liang, W.; Shen, L. Association of serum C1q/TNF-related protein-3 (CTRP-3) in patients with coronary artery disease. BMC Cardiovasc. Disord. 2017, 17, 210. [Google Scholar] [CrossRef] [Green Version]
  14. Svestak, M.; Sporova, L.; Hejduk, P.; Lacnak, B.; Stejskal, D. Collagenous repeatcontaining sequence of 26 kDa protein-a newly discovered adipokine-sensu lato-A minireview. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech. Repub. 2010, 154, 199–202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Famulla, S.; Lamers, D.; Hartwig, S.; Passlack, W.; Horrighs, A.; Cramer, A. Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. Int. J. Obes. 2011, 35, 762–772. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. He, X.; Cheng, R.; Benyajati, S.; Ma, J. PEDF and its roles in physiological and pathological conditions: Implication in diabetic and hypoxia-induced angiogenic diseases. Clin. Sci. 2015, 128, 805–823. [Google Scholar] [CrossRef] [Green Version]
  17. Becerra, S.P. Structure-function studies on PEDF. A noninhibitory serpin with neurotrophic activity. Adv. Exp. Med. Biol. 1997, 425, 223–237. [Google Scholar]
  18. Tombran-Tink, J.; Mazuruk, K.; Rodriguez, I.R.; Chung, D.; Linker, T.; Englander, E.; Chader, G.J. Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. Mol. Vis. 1996, 2, 11. [Google Scholar]
  19. Uhlen, M.; Fagerberg, L.; Hallstrom, B.M.; Lindskog, C.; Oksvold, P.; Mardinoglu, A.; Sivertsson, A.; Kampf, C.; Sjostedt, E.; Asplund, A. Proteomics. Tissue-based map of the human proteome. Science 2015, 347, 1260419. [Google Scholar] [CrossRef]
  20. Tombran-Tink, J.; Chader, G.G.; Johnson, L.V. PEDF: A pigment epithelium-derived factor with potent neuronal differentiative activity. Exp. Eye Res. 1991, 53, 411–414. [Google Scholar] [CrossRef] [Green Version]
  21. Notari, L.; Baladron, V.; Aroca-Aguilar, J.D.; Balko, N.; Heredia, R.; Meyer, C.; Notario, P.M.; Saravanamuthu, S.; Nueda, M.L.; Sanchez-Sanchez, F.; et al. Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J. Biol. Chem. 2006, 281, 38022–38037. [Google Scholar] [CrossRef] [Green Version]
  22. Nelson, J.; McFerran, N.V.; Pivato, G.; Chambers, E.; Doherty, C.; Steele, D.; Timson, D.J. The 67 kDa laminin receptor: Structure, function and role in disease. Biosci. Rep. 2008, 28, 33–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Chuderland, D.; Ben-Ami, I.; Bar-Joseph, H.; Shalgi, R. Role of pigment epithelium-derived factor in the reproductive system. Reproduction 2014, 148, 53–61. [Google Scholar] [CrossRef] [Green Version]
  24. Borg, M.L.; Andrews, Z.B.; Duh, E.J.; Zechner, R.; Meikle, P.J.; Watt, M.J. Pigment epithelium-derived factor regulates lipid metabolism via adipose triglyceride lipase. Diabetes 2011, 60, 1458–1466. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  25. Li, T.H.; Qiu, C.J.; Yu, X.J.; Liu, D.D.; Zhou, P.F.; Wu, L. Increased Serum Pigment Epithelium-Derived Factor in Women with Gestational Diabetes Is Associated with Type 2 Diabetes. Intl. J. Endocrinol. 2015, 2015, 346938. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Metzger, B.E.; Gabbe, S.G.; Persson, B.; Buchanan, T.A.; Catalano, P.A.; Damm, P.; Dyer, A.R.; Leiva, A.; Hod, M.; Kitzmiler, J.L.; et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010, 33, 676–682. [Google Scholar] [CrossRef] [Green Version]
  27. Anna, V.; van der Ploeg, H.P.; Cheung, N.W.; Huxley, R.R.; Bauman, A.E. Sociodemographic correlates of the increasing trend in prevalence of gestational diabetes mellitus in a large population of women between 1995 and 2005. Diabetes Care 2008, 31, 2288–2293. [Google Scholar] [CrossRef] [Green Version]
  28. Ferrara, A.; Kahn, H.S.; Quesenberry, C.P.; Riley, C.; Hedderson, M.M. An increase in the incidence of gestational diabetes mellitus: Northern California, 1991–2000. Obstet. Gynecol. 2004, 103, 526–533. [Google Scholar] [CrossRef]
  29. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2017, 40, 11–24. [Google Scholar] [CrossRef] [Green Version]
  30. Bener, A.; Saleh, N.M.; Al-Hamaq, A. Prevalence of gestational diabetes and associated maternal and neonatal complications in a fast-developing community: Global comparisons. Int. J. Womens Health 2011, 3, 367–373. [Google Scholar] [CrossRef] [Green Version]
  31. Nahavandi, S.; Price, S.; Sumithran, P.; Ekinci, E.I. Exploration of the shared pathophysiological mechanisms of gestational diabetes and large for gestational age offspring. World J. Diabetes 2019, 10, 333–340. [Google Scholar] [CrossRef]
  32. Contreras-Duarte, S.; Carvajal, L.; Garchitorena, M.J.; Subiabre, M.; Fuenzalida, B.; Cantin, C.; Farías, M.; Leiva, A. Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function. Nutrients 2020, 12, 506. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. HAPO Study Cooperative Research Group. The hyperglycemia and adverse pregnancy outcome (HAPO) study. Int. J. Gynaecol. Obstet. 2002, 78, 69–77. [Google Scholar] [CrossRef]
  34. Shah, B.R.; Retnakaran, R.; Booth, G.L. Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care 2008, 31, 1668–1669. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Teede, H.J.; Harrison, C.L.; Teh, W.T.; Paul, E.; Allan, C.A. Gestational diabetes: Development of an early risk prediction tool to facilitate opportunities for prevention. Aust. N. Zeal. J. Obstet. Gynaecol. 2011, 51, 499–504. [Google Scholar] [CrossRef]
  36. Fasshauer, M.; Blüher, M.; Stumvoll, M. Adipokines in gestational diabetes. Lancet Diabetes Endocrinol. 2014, 2, 488–499. [Google Scholar] [CrossRef]
  37. Xiang, A.H.; Peters, R.K.; Trigo, E.; Kjos, S.L.; Lee, W.P.; Buchanan, T.A. Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. Diabetes 1999, 48, 848–854. [Google Scholar] [CrossRef]
  38. Hofmann, C.; Chen, N.; Obermeier, F.; Paul, G.; Büchler, C.; Kopp, A.; Falk, W.; Schäffler, A. C1q/TNF-related protein-3 (CTRP-3) is secreted by visceral adipose tissue and exerts antiinflammatory and antifibrotic effects in primary human colonic fibroblasts. Inflamm. Bowel Dis. 2011, 17, 2462–2471. [Google Scholar] [CrossRef]
  39. Ban, B.; Bai, B.; Zhang, M.; Hu, J.; Ramanjaneya, M.; Tan, B.K.; Chen, J. Low serum cartonectin/CTRP3 concentrations in newly diagnosed type 2 diabetes mellitus: In vivo regulation of cartonectin by glucose. PLoS ONE 2014, 9, e112931. [Google Scholar] [CrossRef] [Green Version]
  40. Li, X.; Jiang, L.; Yang, M.; Wu, Y.W.; Sun, J.Z.; Sun, S.X. CTRP3 improves the insulin sensitivity of 3T3-L1 adipocytes by inhibiting inflammation and ameliorating insulin signalling transduction. Endokrynol. Polska 2014, 65, 252–258. [Google Scholar] [CrossRef] [Green Version]
  41. Li, X.; Jiang, L.; Yang, M.; Wu, Y.; Sun, S.; Sun, J. GLP-1 receptor agonist increases the expression of CTRP3, a novel adipokine, in 3T3-L1 adipocytes through PKA signal pathway. J. Endocrinol. Investig. 2015, 38, 73–79. [Google Scholar] [CrossRef]
  42. Qu, H.; Deng, M.; Wang, H.; Wei, H.; Liu, F.; Wu, J.; Deng, H. Plasma CTRP-3 concentrations in Chinese patients with obesity and type II diabetes negatively correlate with insulin resistance. J. Clin. Lipidol. 2015, 9, 289–294. [Google Scholar] [CrossRef] [PubMed]
  43. Choi, K.M.; Hwang, S.Y.; Hong, H.C.; Yang, S.J.; Choi, H.Y.; Yoo, H.J.; Lee, K.W.; Nam, M.S.; Park, Y.S.; Woo, J.T.; et al. C1q/TNF-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF) concentrations in patients with type 2 diabetes and metabolic syndrome. Diabetes 2012, 61, 2932–2936. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Wei, H.; Qu, H.; Wang, H.; Deng, H. Plasma C1q/TNF-Related Protein-3 (CTRP-3) and High-Mobility Group Box-1 (HMGB-1) Concentrations in Subjects with Prediabetes and Type 2 diabetes. J. Diabetes Res. 2016, 2016, 9438760. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Wolf, R.M.; Steele, K.E.; Peterson, L.A.; Magnuson, T.H.; Schweitzer, M.A.; Wong, G.W. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3) Levels Are Associated with Obesity: A Cross-Sectional Study. PLoS ONE 2015, 10, e0133955. [Google Scholar] [CrossRef] [PubMed]
  46. Wagner, R.M.; Sivagnanam, K.; Clark, W.A.; Peterson, J.M. Divergent relationship of circulating CTRP3 levels between obesity and gender: A cross-sectional study. PeerJ 2016, 4, e2573. [Google Scholar] [CrossRef] [Green Version]
  47. Moradi, N.; Fadaei, R.; Khamseh, M.E.; Nobakht, A.; Rezaei, M.J.; Aliakbary, F.; Vatannejad, A.; Hosseini, J. Serum levels of CTRP3 in diabetic nephropathy and its relationship with insulin resistance and kidney function. PLoS ONE 2019, 14, e0215617. [Google Scholar] [CrossRef] [Green Version]
  48. Huang, N.; Zhang, X.; Jiang, Y.; Mei, H.; Zhang, L.; Zhang, Q.; Hu, J.; Chen, B. Increased levels of serum pigment epithelium-derived factor aggravate proteinuria via induction of podocyte actin rearrangement. Int. Urol. Nephrol. 2019, 51, 359–367. [Google Scholar] [CrossRef] [Green Version]
  49. Anastas, J.N.; Moon, R.T. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 2013, 13, 11–26. [Google Scholar] [CrossRef]
  50. Chen, H.; Zheng, Z.; Li, R.; Lu, J.; Bao, Y.; Ying, X.; Zeng, R.; Jia, W. Urinary pigment epithelium-derived factor as a marker of diabetic nephropathy. Am. J. Nephrol. 2010, 32, 47–56. [Google Scholar] [CrossRef]
  51. Jenkins, A.J.; Zhang, S.X.; Rowley, K.G.; Karschimkus, C.S.; Nelson, C.L.; Chung, J.S.; O’Neal, D.N.; Januszewski, A.S.; Croft, K.D.; Mori, T.A.; et al. Increased serum pigment epithelium-derived factor is associated with microvascular complications. vascular stiffness and inflammation in Type 1 diabetes. Diabet. Med. 2007, 24, 1345–1351. [Google Scholar] [CrossRef]
  52. Nakamura, K.; Yamagishi, S.; Adachi, H.; Kurita-Nakamura, Y.; Matsui, T.; Inoue, H. Serum levels of pigment epithelium-derived factor (PEDF) are positively associated with visceral adiposity in Japanese patients with type 2 diabetes. Diabetes Metab. Res. Rev. 2009, 25, 52–56. [Google Scholar] [CrossRef] [PubMed]
  53. Yang, S.; Li, Q.; Zhong, L.; Song, Y.; Tian, B.; Cheng, Q. Serum pigment epithelium-derived factor is elevated in women with polycystic ovary syndrome and correlates with insulin resistance. J. Clin. Endocrinol. Metab. 2011, 96, 831–836. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Chen, C.; Tso, A.W.; Law, L.S.; Cheung, B.M.; Ong, K.L.; Wat, N.M. Plasma level of pigment epithelium-derived factor is independently associated with the development of the metabolic syndrome in Chinese men: A 10-year prospective study. J. Clin. Endocrinol. Metab. 2010, 95, 5074–5081. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Jenkins, A.; Zhang, S.X.; Gosmanova, A.; Aston, C.; Dashti, A.; Baker, M.Z.; Lyons, T.; Ma, J.X. Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients. Diabetes Res. Clin. Prac. 2008, 82, 5–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Huang, K.T.; Lin, C.C.; Tsai, M.C.; Chen, K.D.; Chiu, K.W. Pigment epithelium-derived factor in lipid metabolic disorders. Biomed. J. 2018, 41, 102–108. [Google Scholar] [CrossRef]
  57. Sinclair, S.H.; Schwartz, S.S. Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes. Front. Endocrinol. 2019, 10, 843. [Google Scholar] [CrossRef] [Green Version]
  58. Sabater, M.; Moreno-Navarrete, J.M.; Ortega, F.J.; Pardo, G.; Salvador, J.; Ricart, W.; Frühbeck, G.; Fernández-Real, J.M. Circulating pigment epithelium-derived factor levels are associated with insulin resistance and decrease after weight loss. J. Clin. Endocrinol. Metab. 2010, 95, 4720–4728. [Google Scholar] [CrossRef]
  59. Wang, P.; Smit, E.; Brouwers, M.C.; Goossens, G.H.; van der Kallen, C.J.; van Greevenbroek, M.M.; Mariman, E.C. Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depot. Eur. J. Endocrinol. 2008, 159, 713–718. [Google Scholar] [CrossRef] [Green Version]
  60. Ahima, R.S. Adipose tissue as an endocrine organ. Obesity 2006, 14, 242–249. [Google Scholar] [CrossRef] [PubMed]
  61. Crowe, S.; Wu, L.E.; Economou, C.; Turpin, S.M.; Matzaris, M.; Hoehn, K.L.; Hevener, A.L.; James, D.E.; Duh, E.J.; Watt, M.J. Pigment epithelium-derived factor contributes to insulin resistance in obesity. Cell Metab. 2009, 10, 40–47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Yamagishi, S.; Adachi, H.; Abe, A.; Yashiro, T.; Enomoto, M.; Furuki, K.; Hino, A.; Jinnouchi, Y.; Takenaka., K.; Matsui, T.; et al. Elevated serum levels of pigment epithelium-derived factor in the metabolic syndrome. J. Clin. Endocrinol. Metab. 2006, 91, 2447–2450. [Google Scholar] [CrossRef] [PubMed]
  63. Filleur, S.; Nelius, T.; de Riese, W.; Kennedy, R.C. Characterization of PEDF: A multi-functional serpin family protein. J. Cell. Biochem. 2009, 106, 769–775. [Google Scholar] [CrossRef] [PubMed]
Jcm 09 02587 g001 550
Figure 1. Flowchart of participant recruitment and case–control study.
Figure 1. Flowchart of participant recruitment and case–control study.
Jcm 09 02587 g001
Jcm 09 02587 g002 550
Figure 2. Comparisons of C1q/tumor necrosis factor-related protein-3 (CTRP-3) serum concentration according to occurrence of gestational diabetes mellitus (GDM) and treatment. *—statistically significant differences (p < 0.05).
Figure 2. Comparisons of C1q/tumor necrosis factor-related protein-3 (CTRP-3) serum concentration according to occurrence of gestational diabetes mellitus (GDM) and treatment. *—statistically significant differences (p < 0.05).
Jcm 09 02587 g002
Table
Table 1. Characteristic of the study and control groups. Comparison of the distribution of selected clinical factors according to groups.
Table 1. Characteristic of the study and control groups. Comparison of the distribution of selected clinical factors according to groups.
VariableControl (C)GDM1GDM2GDM (1 + 2)C vs.
GDM (1 + 2)		C vs. GDM1C vs. GDM 2GDM1 vs. GDM2
n = 54 (%)n = 75 (%)n = 43 (%)n = 118 (%)p
Pregnancy [n] 0.48710.13120.35860.0115
126 (48.15)49 (65.33)16 (37.21)65 (55.08)
218 (33.33)15 (20.00)14 (32.56)29 (24.58)
>210 (18.52)11 (14.67)13 (30.23)24 (20.34)
Labor [n] 0.78520.23680.40060.0138
132 (59.26)55 (73.33)20 (46.51)75 (63.56)
215 (27.78)13 (17.33)14 (32.56)27 (22.88)
>27 (12.96)7 (9.33)9 (20.93)16 (13.56)
Labor Type 0.51170.43110.89310.7283
Vaginal delivery22 (40.74)37 (49.33)19 (44.19)56 (47.46)
Caesarean section32 (59.26)38 (50.67)24 (55.81)62 (52.54)
Preterm Labor 0.10860.39130.02820.1782
No53 (98.15)70 (93.33)36 (83.72)106 (89.83)
Yes1 (1.85)5 (6.67)7 (16.28)12 (10.17)
Sex of the Newborn 0.63540.99010.14280.0815
Girl28 (51.85)40 (53.33)15 (34.88)55 (46.61)
Boy26 (48.15)35 (46.67)28 (65.12)63 (53.39)
APGAR 1 0.01250.00060.62960.0279
1036 (66.67)26 (33.77)25 (58.14)51 (43.22)
915 (27.78)35 (45.45)14 (32.56)49 (41.53)
<93 (5.55)16 (20.78)4 (9.30)18 (15.25)
BMI (before Pregnancy) [kg/m 2] 0.00140.00550.00050.1287
<18.503 (5.56)6 (8.00)-6 (5.08)
18.50–24.9945 (83.33)43 (57.33)24 (55.81)67 (56.78)
>24.996 (11.11)26 (34.67)19 (44.19)45 (38.14)
C-control group, GDM-gestational diabetes mellitus, BMI-body mass index.
Table
Table 2. Comparison of values of selected factors between different groups.
Table 2. Comparison of values of selected factors between different groups.
VariableControl (C)
(n = 54)		GDM1
(n = 75)		GDM2
(n = 43)		GDM (1 + 2)
(n = 118)		C vs. GDM (1 + 2)C vs. GDM1 vs. GDM2
Me (Interquartile Range)p
Age [years]29.00 (26.00–34.00)32.00 (28.00–35.00)31.00 (27.00–36.00)32.00 (28.00–35.00)0.07330.1980
Glucose [mg/dL]60.04 (52.72–66.21)67.11 (51.95–75.21)66.43 (55.98–76.75)66.62 (54.70–75.92)0.00130.0055
(C vs. GDM1; C vs. GDM2)
Insulin [uLU/mL]11.77 (7.44–17.98)11.40 (6.69–18.44)12.94 (8.43–22.68)12.50 (8.18–19.67)0.67760.3761
OGTT (Fasting) [mg/dL]79.50 (77.00–84.00)82.00 (79.00–88.00)88.00 (82.00–93.00)85.00 (80.00–89.00)<0.0001<0.0001
(C vs. GDM1; C vs. GDM2; GDM1 vs. GDM2)
OGTT (75g 2 h) [mg/dL]110.00 (93.00–119.00)158.00 (155.00–162.00)160.00 (155.00–169.00)159.00 (155.00–165.50)<0.0001<0.0001
(C vs. GDM1; C vs. GDM2)
HOMA-IR1.58 (1.22–2.50)1.75 (1.15–3.11)2.05 (1.48–3.67)1.96 (1.18–3.43)0.09540.0857
PEDF [ng/mL]40.67 (31.05–119.37)38.25 (32.54–163.24)54.96 (28.91–186.57)42.07 (32.25–163.24)0.97890.8543
CTRP3 [ng/mL]4.79 (2.74–12.12)8.40 (1.99–18.66)10.96 (3.17–25.59)8.84 (2.60–18.98)0.02650.0178
(C vs. GDM1; C vs. GDM2)
Pregnancy [n]2.00 (1.00–2.00)1.00 (1.00–2.00)2.00 (1.00–3.00)1.00 (1.00–2.00)0.80700.0421
(GDM1 vs. GDM2)
Labor [n]1.00 (1.00–2.00)1.00 (1.00–2.00)1.50 (1.00–2.00)1.00 (1.00–2.00)0.63490.1116
Gestational Age at Birth [weeks]40.00 (38.60–41.00)39.00 (38.00–39.00)38.00 (37.00–39.00)38.40 (37.55–39.00)<0.0001<0.0001
Birth weight of the Newborn [g]3435.00 (3170.00–3840.00)3370.00 (3100.00–3790.00)3400.00 (3130.00–3650.00)3375.00 (3100.00–3780.00)0.36980.6619
APGAR 110.00 (9.00–10.00)9.00 (9.00–10.00)10.00 (9.00–10.00)9.00 (9.00–10.00)0.05900.0029
(C vs. GDM1; GDM1 vs. GDM2)
APGAR 5--10.00 (5.00–10.00)10.00 (5.00–10.00)1.00001.0000
BMI (before pregnancy) [kg/m2]23.28 (21.48–24.38)23.23 (21.48–25.78)24.22 (22.77–27.82)23.44 (22.09–26.15)0.03410.0164
(C vs. GDM2; GDM1 vs GDM2)
Weight (Baseline) [kg]65.00 (59.00–69.00)65.00 (60.00–75.00)66.00 (60.00–76.00)65.00 (60.00–75.00)0.05660.1431
Weight (Current) [kg]76.50 (72.00–83.00)79.50 (74.00–85.00)78.50 (72.50–86.50)79.00 (74.00–86.00)0.10480.2640
Height [cm]167.00 (163.00–171.00)167.00 (164.00–170.00)166.50 (162.00–170.00)167.00 (164.00–170.00)0.99450.7559
Increase of Weight during Pregnancy [kg]14.00 (11.00–16.00)13.00 (12.00–15.00)11.50 (7.00–14.00)12.50 (10.00–15.00)0.10660.1213
Data were presented as the median (Me) and interquartile range. C-control group, GDM-gestational diabetes mellitus, BMI-body mass index, OGTT-oral glucose tolerance test, PEDF-pigment epithelium-derived factor, CTRP-3C1q/tumor necrosis factor-related protein-3.
Table
Table 3. Correlation between selected factors and Pigment Epithelium-Derived Factor (PEDF) [ng/mL].
Table 3. Correlation between selected factors and Pigment Epithelium-Derived Factor (PEDF) [ng/mL].
VariableControlGDM1GDM2GDM (1 + 2)
rhoprhoprhoprhop
Age [years]−0.4120.0020−0.0740.5420−0.1030.5119−0.0970.3053
Glucose [mg/dL]0.0120.93060.0240.8377−0.1420.3648−0.0380.6860
Insulin [uLU/mL]0.0080.9553−0.0890.44700.1100.48200.0080.9287
OGTT (Fasting) [mg/dL]0.0410.76910.0590.61490.0870.58170.0460.6267
OGTT (75 g 2 h) [mg/dL]−0.0860.53630.1140.33420.2390.12680.1560.0940
HOMA-IR−0.0060.9657−0.0610.60400.0380.8067−0.0010.9878
Pregnancy [n]−0.2050.1407−0.1280.29330.0610.7026−0.0330.7283
Labor [n]−0.2200.1129−0.1040.3967−0.0010.9937−0.0530.5857
Gestational Age [weeks]0.0350.8048−0.0450.70890.0010.9967−0.0570.5525
Birth weight of the Newborn [g]0.0660.64020.0950.43560.0420.79490.0120.9040
APGAR 1−0.1460.33430.0590.66460.3300.06990.1720.1098
APGAR 2----0.8250.01170.8250.0117
BMI (before Pregnancy) [kg/m2]−0.0790.5693−0.0190.8748−0.3510.0210−0.1280.1711
Weight (Initial) [kg]0.0010.9961−0.2950.0719−0.1910.2381−0.2290.0438
Weight (Current) [kg]0.0750.5920−0.0190.8761−0.1430.3799−0.1010.2930
Height [cm]0.2260.09990.1140.34410.0520.75040.0560.5601
Increase of Weight during Pregnancy [kg]0.2900.0504−0.3130.05560.0950.5600−0.0830.4696
Table
Table 4. Correlation between selected factors and CTRP3 [ng/ml].
Table 4. Correlation between selected factors and CTRP3 [ng/ml].
VariableControlGDM1GDM2GDM (1 + 2)
rhoprhoprhoprhop
Age [years]−0.0810.56310.1170.3382−0.0140.92650.0430.6499
Glucose [mg/dL]0.0430.7593−0.0200.8654−0.0870.5812−0.0480.6037
Insulin [uLU/mL]−0.2150.12250.1450.21640.3330.02930.2080.0243
OGTT (Fasting) [mg/dl]−0.0960.49530.0950.42490.1360.39200.1290.1706
OGTT (75 g 2 h) [mg/dL]−0.1450.3003−0.1360.25170.0290.8567−0.0340.7155
HOMA-IR−0.2210.11250.1240.29430.2400.12140.1710.0651
PEDF [ng/mL]0.1110.43000.2100.07310.2520.10260.1580.0892
Pregnancy [n]−0.0600.6729−0.0010.99510.0620.69540.0190.8417
Labor [n]−0.0880.53360.0530.66710.0990.54490.0770.4277
Gestational Age [weeks]0.0050.9742−0.1630.1815−0.3820.0126−0.2540.0070
Birth Weight of the Newborn [g]−0.0450.7531−0.0680.58090.0000.9989−0.0500.6090
APGAR 10.1150.4510−0.2140.11360.1000.5935−0.0520.6356
APGAR 2----0.5360.17080.5360.1708
BMI (before Pregnancy) [kg/m2]0.0750.5926−0.1130.3433−0.0370.8123−0.0730.4389
Weight (Baseline) [kg]−0.1320.3819−0.2110.20960.1210.4568−0.0110.9252
Weight (Current) [kg]0.0080.9542−0.2560.03410.1880.2465−0.0800.4081
Height [cm]−0.0860.5423−0.1730.15120.2360.1433−0.0330.7327
Increase of Weight during Pregnancy [kg]0.0270.8610−0.3520.03260.1260.4381−0.0520.6507

Share and Cite

MDPI and ACS Style

Gęca, T.; Kwiatek, M.; Krzyżanowski, A.; Kwaśniewska, A. C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study. J. Clin. Med. 2020, 9, 2587. https://doi.org/10.3390/jcm9082587

AMA Style

Gęca T, Kwiatek M, Krzyżanowski A, Kwaśniewska A. C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study. Journal of Clinical Medicine. 2020; 9(8):2587. https://doi.org/10.3390/jcm9082587

Chicago/Turabian Style

Gęca, Tomasz, Maciej Kwiatek, Arkadiusz Krzyżanowski, and Anna Kwaśniewska. 2020. "C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study" Journal of Clinical Medicine 9, no. 8: 2587. https://doi.org/10.3390/jcm9082587

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop