Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1436-1441

Chemerin as a predictor for gestational diabetes mellitus


1 Department of Clinical Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission20-Jan-2022
Date of Decision07-Mar-2022
Date of Acceptance08-Mar-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Manal F Al Hassanean
Department of Clinical Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Berket Elsaba, Menoufia
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_32_22

Rights and Permissions
  Abstract 


Objective
This study was conducted to assess the chemerin level and detect its role as a predictor for gestational diabetes mellitus (GDM) by studying the relation between the serum chemerin level in the first trimester and the development of GDM.
Background
Chemerin is an adipokine that regulates adipocyte development and metabolic function as well as glucose metabolism in liver and skeletal muscle tissue. GDM is defined as glucose intolerance first recognition during pregnancy. The incidence of GDM is increasing year by year all over the world, especially in developing countries.
Patients and methods
This case–control study has been conducted on a total number of 162 pregnant women during the first trimester of pregnancy, divided into two groups according to their body mass index (BMI): Group 1: normal weight and Group 2: overweight, marked or morbidly obese. Participants were selected from those attending Obstetrics and Gynecology Outpatient Clinic, Birket Al Sabaa Hospital. Based on the past review of literature that assumed the prevalence of gestational diabetes to be 13.2%, sample size has been calculated and it was 162 patients.
Results
Based on the current results, gestational diabetes was diagnosed among 12.3% (20 patients), 142 free gestational diabetes ones. In the present study, we found that weight and BMI were significantly higher among GDM group than non-GDM one. Elevated levels of chemerin were found among women with GDM.
Conclusions
Serum chemerin level measured from a single blood sample may be used as a marker for prediction of GDM specially in overweight or obese women. Weight and BMI were significantly higher among GDM group than non-GDM one.

Keywords: adipokine, diabetic women, early pregnancy, gestational diabetes mellitus, serum chemerin level


How to cite this article:
Abd El All NK, El Halaby AE, Nofal AM, Al Hassanean MF, Kasemy ZA. Chemerin as a predictor for gestational diabetes mellitus. Menoufia Med J 2022;35:1436-41

How to cite this URL:
Abd El All NK, El Halaby AE, Nofal AM, Al Hassanean MF, Kasemy ZA. Chemerin as a predictor for gestational diabetes mellitus. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1436-41. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1436/359500




  Introduction Top


Chemerin is an adipokine that regulates adipocyte development and metabolic function as well as glucose metabolism in the liver and skeletal muscle tissue[1].

Chemerin is expressed in the body's adipose tissue, adrenal gland, liver, lung, pancreas, placenta, ovary, and skin particularly in white adipose tissue[2].

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. The incidence of GDM is increasing year by year all over the world, especially in developing countries. GDM is one of the common pregnancy complications and endangers the health of both pregnant women and the fetus. It may lead to maternal metabolic disorders, which in turn increase the risk to the mother and child such as large for gestational age in unmanaged GDM, small for gestational age and intrauterine growth retardation in managed GDM, spontaneous abortion, fetal malformation, neonatal hypoglycemia, jaundice, polycythemia, hypocalcemia, and hypomagnesemia[3].

It is very important to predict GDM as early as possible to prevent any complications. Human adipose tissue as one of the most important endocrine organ synthesizes and secretes a variety of adipocytokines, including leptin, tumor necrosis factor-a, interleukin-6, and newly discovered resistin, visfatin, apelin, fasting-induced adipose factor, retinol-binding 4, chemerin, and so on. Chemerin can be involved in inflammation and regulate glucose and lipid metabolism. The expression of chemerin is related to obesity.

Chemerin has the biological effects of regulating adipocyte differentiation and lipolysis as well as promoting the insulin signal transduction pathway in adipose cells[1].

As a newly recognized adipose factor, chemerin is attracting more and more attention and in-depth research in obesity, insulin resistance, metabolic syndrome, and its influence on the development of type 2 diabetes. However, the understanding of chemerin is still incomprehensive and some problems remain to be clarified as it is a newly discovered area and there are racial differences[4]. This study aimed to assess chemerin level and detect its role as a predictor for GDM by studying the relation between serum chemerin level in the first trimester and the development of GDM.


  Participants and methods Top


This cohort study has been conducted on a total number of 162 pregnant women during the first trimester of pregnancy, divided into two groups according to their body mass index (BMI): Group 1 normal weight And Group 2 overweight, marked, or morbidly obese. Participants were selected from those attending Obstetrics and Gynecology Outpatient Clinic, Birket Al Sabaa Hospital. Inclusion criteria were primigravida singleton pregnancy, gestational age between 6 and 12 weeks, and women with intact membranes. Exclusion criteria were pregnancies complicated by hypertension, another metabolic disease, alcohol abuse, L or drug abuse, diabetic women and/or pregestational diabetes, multiple pregnancies, and multipara women. The study was explained to all enrolled women and written informed consent was taken from all participants. All patients were subjected to history taken, clinical examinations, and ultrasound investigations as follows. History taking: including personal history: name, age, marital status, residence, occupation, and special habits if present, complaint if present. Present history: medical illness or any surgical interference and pelvic operation. Obstetric history: all of them are primigravida. Clinical examination: general examination, including vital signs as pules, temperature, blood, pressure, and general appearance. The authors assessed at the first trimester for chemerin. Local examination: inspection of any ulcer, swelling, or scar. Investigations: abdominal ultrasound. Ethical considerations: the study started after the approval of the protocol by the ethical committee of Faculty of Medicine, Department of Obstetrics, and Gynecology, Menoufia University for each patient included in the study. The following procedure was done: explaining the importance of the study to the patient to become more interested and cooperative. The confidentiality of the patient's data was guaranteed. The patient had the right to refuse participation in this study at any time they want without giving any reason. Informed consent was taken from patients after an explanation of the procedure to be done. The patients were 16–35 years of age and primigravida had singleton pregnancies. Pregnant women who presented themselves to our obstetrics department were screened between 24 and 28 weeks of gestation for GDM according to the recommendations of the American College of Obstetricians and Gynecologists. Briefly, all pregnant women in the low-risk group were evaluated with a 50-g glucose challenge test. Women with serum glucose ≥ 140 mg/dl at 1 h after glucose challenge test were subjected to a 100-g oral glucose tolerance test. Serum glucose concentrations were measured at 0, 1, 2, and 3 h after glucose ingestion. The diagnosis of GDM was based on the criteria of Carpenter and Couston[5] in which, after a 100-g oral glucose load, two or more of the following plasma values must be obtained: fasting ≥ 95 mg/dl, 1 h ≥ 180 mg/dl, 2 h ≥ 155 mg/dl, and 3 h ≥ 140 mg/dl. The estimation of pregnancy duration was based on routine ultrasonography examination performed in the first trimester. BMI was calculated using pregnancy weight and height, which were recorded at the time of blood sampling. A total of 162 pregnant women met the inclusion criteria and were divided into two groups: 81 were in the normal weight group, and 81 were in the overweight, obese, morbid obese group. The demographic characteristics and biochemical parameters of the study population, including age, BMI, and gestational age, were recorded in the first trimester. Assays and detection method: elbow venous blood (5 ml) was extracted from participants' stomach in the morning and then placed in a vacuum tube without anticoagulant and centrifuged at 2600 × g for 10 min at 4°C. The serum was stored in EP tube for later use and placed in a low temperature refrigerator at − 75°C. The serum was taken from the freezer, placed in the refrigerator at 4°C for dissolution and then placed at room temperature for complete dissolution. Enzyme-linked immunosorbent assay was used to detect the expression of chemerin[5]. The test was carried out in strict accordance with the specifications of the human chemerin Elisa kit. The sample well, standard sample well, and blank well were set up. Sample (50 ul) to be tested. No reagent was added to the blank wall. Serum insulin concentration was measured by chemiluminescence assay. Homeostasis model assessment-insulin resistance (HOMA-IR) was calculated using the following formula: Plasma glucose (mg/dl)×fasting plasma insulin (IUmg/l) in the fasting state divided by 405.

Statistical analysis

The statistical analysis was done using IBM-SPSS-25 (Inc., Chicago, IL, USA). Statistical analysis was performed using descriptive variables, for example, percentage (%), mean, and SD and analytical variables, including t-test, Mann-Whitney, correlation coefficient (Person testing), and c2 tests. At P < 0.05, the results were judged to have statistical significance.


  Results Top


Weight and BMI were significantly higher among the GDM group (83.9 ± 16.8 and 31.70 ± 6.3, respectively) than non-GDM one (67.0 ± 11.5 and 24.9 ± 3.4, respectively) (P < 0.001) [Table 1].
Table 1: General characteristics of studied groups

Click here to view


Fasting blood glucose (FBG), 2-h postprandial plasma, and serum chemerin were significantly higher among GDM group (4.80 ± 0.6, 8.9 ± 0.4, and 173.6 ± 60.4, respectively) than non-GDM one (4.3 ± 0.3, 7.7 ± 0.5, and 101.2 ± 51.8, respectively) (P < 0.01) [Table 2].
Table 2: Distribution of FBG, 2 h postprandial, HOMA-IR, and chemerin level among the studied groups

Click here to view


There were significant correlations between serum chemerin and weight, gestational age, FBG, 2-h postprandial plasma, and HOMA-IR (P < 0.05) [Table 3].
Table 3: Correlation between serum chemerin and different parameters in each group

Click here to view



  Discussion Top


This work aims to assess chemerin level and detect its role as a predictor for GDM by studying the relation between serum chemerin level in the first trimester and the development of GDM.

In the present study, we found that weight and BMI were significantly higher among the GDM group than non-GDM one.

GDM is defined as varying degrees of glucose intolerance first detected during pregnancy, which affects 4–18% of pregnant women according to different diagnostic criteria and ethnic origin[6]. The pathophysiologic mechanism of GDM is similar to type 2 diabetes mellitus, including insulin resistance, oxidative stress, and systemic inflammation[7].

Chemerin is a novel cytokine mainly secreted from white adipose tissues, which was initially considered as a chemotactic factor generated in inflammatory conditions, but more recently, it was reported more as an adipokine regulating the metabolism of adipose and balance of energy[8].

It is also suggested that pregnant women who develop GDM may have preexisting β-cell defects unable to adapt to the increasing demands of insulin during pregnancy[9]. And now it is widely believed that systemic inflammation is associated with β-cell dysfunction and the subsequent insulin resistance in diabetic patients[10].

In the present study, the incidence of GDM among women was 12.3%. The result was consistent with the findings of a recent study conducted in Ethiopia as they reported the prevalence of GDM among women in Tigray, Ethiopia (12.8%)[11]. The finding was higher than those of studies conducted in Rwanda (8.3%)[12] Tanzania (5.9%)[13], and Nigeria (8.6%)[14]. The main reason for the high prevalence of GDM in this study setting might be the fact that the lower cut-off points for FPG and oral glucose tolerance test were used in the updated diagnostic criteria[11].

On the other hand, the finding is lower than those of studies conducted in South Africa (25.8%)[15] that used similar diagnostic criteria. This evidence indicates that the prevalence of GDM might also be affected not only by different diagnostic criteria but also by the characteristics of the population. Increased testing for GDM, change in lifestyle, and the rising prevalence of overweight and obesity might have contributed[16].

In accordance with our findings, a previous study considered obesity using BMI noted its significant association with GDM[17]. This was happened by the fact that the decreased insulin sensitivity in obese pregnancies resulted in increased blood glucose levels. Overweight or obesity exposed to sedentary life led to obesity due to inactive lifestyle. This cycle also adversely affects glucose metabolism[11].

In the present study, we found elevated levels of chemerin among women with GDM. Li et al.[18] found an increase in peripheral circulating chemerin levels in GDM women. However, other studies found no difference in peripheral circulating chemerin levels between GDM women and healthy women[19]. But in these studies, Shao et al.[20] reported an increase in chemerin levels in cord blood, and the latter two also observed an increase in the placenta.

Conversely, another study reported lower levels of peripheral circulating chemerin in GDM women[21]. There were some differences and even conflicts among the studies, including the present study, and it was speculated that it was caused by several reasons: participant selection and match strategies were different like there were many obese women or women with risk factors in the control group in several studies, which might narrow the difference of chemerin levels between the two groups; the sample size in one study was not large enough that the results might be not so convincing[20]. For GDM women in each study, the severity of patients' condition and the patients' treatment was different from each other, which might also influence the chemerin concentrations.

An increase in chemerin level was often observed in metabolic disorders such as multiple sclerosis (MS), type 2 diabetes mellitus, and GDM[22]. But the mechanism is still unclear. IR may be an important breach; it is widely accepted that IR plays a key role in these diseases; therefore, IR-related factors are probably involved in the pathogenesis of GDM[23].

In the present study, it was observed that maternal serum chemerin level was positively correlated with the HOMA-IR index, which was consistent with previous studies, indicating that the circulating chemerin concentration can be in synchronous change with the progress of GDM and possibly take part in the generation and development of GDM. As for the mechanism from chemerin to IR, it is suggested that inflammation may be mediation in this mechanism. Chemerin has multidimensional functions including the preinflammation role; it is generally accepted that chemerin and its receptors can recruit macrophages and dendritic cells, and even activate neutrophils, then promote inflammation[24].

On the other hand, much evidence shows that inflammation, especially chronic low-grade inflammation, probably promotes IR[25].

More interestingly, Huang and Xie[26] reported that chemerin could induce IR in C2C12 cells through nuclear factor-kB pathway-mediated inflammatory reaction. In addition, chemerin may influence IR in other ways like regulating b-cell function, somehow[27].

In the present study, we found that serum chemerin was positively correlated with gestational age. In accordance with our finding, serum chemerin levels were found to be low during early pregnancy and rose toward late pregnancy. The high levels of chemerin at the end of the pregnancy might suggest that chemerin also plays a role in the transport of nutrients to influence fetal growth and chemerin might be involved as a regulatory factor in an adaptive response to the subsequent elevated metabolic demands of pregnancy and lactation[28].

In the present study, we found a positive correlation between chemerin and FBG and 2 h postprandial blood glucose. This can be explained as chemerin inhibits glycogen synthase kinase phosphorylation, an enzyme necessary for glycogen synthesis and storage, and thus inhibits glucose uptake[29].

In the present study, Receiver operating characteristic (ROC) curve analysis for serum chemerin to diagnose GDM with sensitivity was 80% and specificity of 71% and area under the curve (AUC) was 0.81. Wang et al.[9] found that the AUC of the peripheral blood of chemerin for diagnosis of GDM patients was 0.820 indicating that peripheral blood of chemerin has good diagnostic value for the diagnosis of GDM patients and can be used as a biomarker for prediction of GDM.


  Conclusion Top


Based on the results of the present study, we conclude that serum chemerin level during the first trimester of pregnancy has the potential to predict the risk of GDM. The meta-analysis supports chemerin as a novel biomarker for the early diagnosis of GDM, which affects many pregnant women. Elevated circulating is a significant factor for metabolic syndrome. It is hypothesized that chemerin is multidimensionally involved in the pathogenesis of metabolic syndrome by regulating meta in inflammation, adipocyte plasticity, and glucose metabolism in humans. The correlation between chemerin and obesity and GDM seems to be well established.

Recommendations

We recommend measuring serum chemerin level during the first trimester to predict GDM specially in obese women. These results could have many implications for the health of pregnant women and their offspring. Our predictive model could become the basis for a selective screening process for GDM diagnosis, and for identification and implementation of early-stage pregnancy interventions to prevent or reduce the development of GDM and its associated adverse health outcomes. Future prospective studies, as well as those on large populations, are needed.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sell H, Laurencikiene J, Taube A, Eckardt K, Cramer A, Horrighs A, et al. Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes 2009; 58:2731–2740.  Back to cited text no. 1
    
2.
Ernst MC, Issa M, Goralski KB, Sinal CJ. Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology 2010; 151:1998–2007.  Back to cited text no. 2
    
3.
Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, et al. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007; 282:28175–28188.  Back to cited text no. 3
    
4.
Rani PR, Begum J. Screening and diagnosis of gestational diabetes mellitus, where do we stand. J Clin Diagn Res 2016; 10:1–10.  Back to cited text no. 4
    
5.
Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144:768–773.  Back to cited text no. 5
    
6.
Simmons D, Jelsma JG, Galjaard S, Devlieger R, van Assche A, Jans G, et al. Results from a European multicenter randomized trial of physical activity and/or healthy eating to reduce the risk of gestational diabetes mellitus: the DALI lifestyle pilot. Diabetes Care 2015; 38:1650–1656.  Back to cited text no. 6
    
7.
Allalou A, Nalla A, Prentice KJ, Liu Y, Zhang M, Dai FF. A predictive metabolic signature for the transition from gestational diabetes mellitus to type 2 diabetes. Diabetes 2016; 65:2529–2539.  Back to cited text no. 7
    
8.
Fatima SS, Rehman R, Baig M, Khan TA. New roles of the multidimensional adipokine: chemerin. Peptides 2014; 62:15–20.  Back to cited text no. 8
    
9.
Wang D, Zhu W, Li J, An C, Wang Z. Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history. PLoS ONE 2013; 8:811–890.  Back to cited text no. 9
    
10.
Nordmann TM, Dror E, Schulze F, Traub S, Berishvili E, Barbieux C, et al. The role of inflammation in β-cell dedifferentiation. Sci Rep 2017; 7:1–10.  Back to cited text no. 10
    
11.
Muche AA, Olayemi OO, Gete YK. Prevalence of gestational diabetes mellitus and associated factors among women attending antenatal care at Gondar town public health facilities, Northwest Ethiopia. BMC Pregnancy Childbirth 2019; 19:1–3.  Back to cited text no. 11
    
12.
Niyibizi JB, Safari F, Ahishakiye JB, Habimana JB, Mapira H, Mutuku NC. Gestational diabetes mellitus and its associated risk factors in pregnant women at selected health facilities in Kigali City, Rwanda. J Diabetes Mellit 2016; 6:269–276.  Back to cited text no. 12
    
13.
Mwanri AW, Kinabo J, Ramaiya K, Feskens EJ. Prevalence of gestational diabetes mellitus in urban and rural Tanzania. Diabetes Res Clin Pract 2014; 103:71–78.  Back to cited text no. 13
    
14.
Olagbuji BN, Atiba AS, Olofinbiyi BA, Akintayo AA, Awoleke JO, Ade-Ojo IP, et al. Prevalence of and risk factors for gestational diabetes using 1999, 2013 WHO and IADPSG criteria upon implementation of a universal one-step screening and diagnostic strategy in a sub-Saharan African population. Eur J Obstet Gynecol Reprod Biol 2015; 189:27–32.  Back to cited text no. 14
    
15.
Adams S, Rheeder P. Screening for gestational diabetes mellitus in a South African population: prevalence, comparison of diagnostic criteria and the role of risk factors. S Afr Med J 2017; 107:523–527.  Back to cited text no. 15
    
16.
Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Aktary WM, et al. Screening and diagnosing gestational diabetes mellitus. Evid Rep Technol Assess (Full Rep) 2012; 5:1111–1121.  Back to cited text no. 16
    
17.
Macaulay S, Ngobeni M, Dunger DB, Norris SA. The prevalence of gestational diabetes mellitus amongst black South African women is a public health concern Diabetes Res Clin Pract 2018; 139:278–287.  Back to cited text no. 17
    
18.
Li XM, Ji H, Li CJ, Wang PH, Yu P, Yu DM. Chemerin expression in Chinese pregnant women with and without gestational diabetes mellitus. Ann Endocrinol (Paris) 2015; 76:19–24.  Back to cited text no. 18
    
19.
Pfau D, Stepan H, Kratzsch J, Verlohren M, Verlohren HJ, Drynda K, et al. Circulating levels of the adipokine chemerin in gestational diabetes mellitus. Horm Res Paediatr 2010; 74:56–61.  Back to cited text no. 19
    
20.
Shao J, Liu M, Li F, Xu X. The expression of chemerin in maternal peripheral, umbilical cord blood and placenta in gestational diabetic patients. J Biomater Tissue Eng 2015; 5:833–837.  Back to cited text no. 20
    
21.
Hare KJ, Bonde L, Svare JA, Randeva HS, Asmar M, Larsen S, et al. Decreased plasma chemerin levels in women with gestational diabetes mellitus. Diabet Med 2014; 31:936–940.  Back to cited text no. 21
    
22.
Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007; 148:4687–4694.  Back to cited text no. 22
    
23.
Liang Z, Zhou M, Xu XK, Qu F, Chen D. Is Chemerin associated with gestational diabetes mellitus? An evidence-based clinical research from Chinese women. J Obstet Gynaecol 2018; 38:482–487.  Back to cited text no. 23
    
24.
Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling, and physiological function of chemerin IUBMB Life 2014; 66:19–26.  Back to cited text no. 24
    
25.
Wieser V, Moschen AR, Tilg H. Inflammation, cytokines and insulin resistance: a clinical perspective. Arch Immunol Ther Exp (Warsz) 2013; 61:119–125.  Back to cited text no. 25
    
26.
Huang Z, Xie X. Chemerin induces insulin resistance in C2C12 cells through nuclear factor-κB pathway-mediated inflammatory reaction. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2015; 31:725–729.  Back to cited text no. 26
    
27.
Takahashi M, Okimura Y, Iguchi G, Nishizawa H, Yamamoto M, Suda K, et al. Chemerin regulates β-cell function in mice. Sci Rep 2011; 1:123.  Back to cited text no. 27
    
28.
Garces MF, Sanchez E, Ruíz-Parra AI, Rubio-Romero JA, Angel-Müller E, Suarez MA, et al. Serum chemerin levels during normal human pregnancy. Peptides 2013; 42:138–143.  Back to cited text no. 28
    
29.
Ali TM, Al Hadidi K. Chemerin is associated with markers of inflammation and predictors of atherosclerosis in Saudi subjects with metabolic syndrome and type 2 diabetes mellitus. Beni Suef Univ J Basic Appl Sci 2013; 2:86–95.  Back to cited text no. 29
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Participants and...
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed524    
    Printed32    
    Emailed0    
    PDF Downloaded64    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]