2014

http://informahealthcare.com/gyeISSN: 0951-3590 (print), 1473-0766 (electronic)

Gynecol Endocrinol, 2014; 30(5): 355–358! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2014.887670

GESTATIONAL DIABETES

Relationship of maternal serum resistin and visfatin levels withgestational diabetes mellitus

Ahmet Karatas1, Nilufer Tuncay Isikkent2, Tulay Ozlu1, and Hilmi Demirin3

1Department of Obstetrics and Gynecology, Medical Faculty, Abant Izzet Baysal University, Bolu, Turkey, 2Department of Obstetrics and Gynecology,

and 3Department of Biochemistry, Medical Faculty, Duzce University, Duzce, Turkey

Abstract

Introduction: Adiponectin, resistin and visfatin are thought to play role in the pathophysiologyof gestational diabetes (GDM). In this study, we aimed to investigate the association of maternalsecond trimester serum resistin and visfatin levels with GDM.Materials and methods: Screening and diagnosis for GDM was performed between the 24–28thgestational weeks. About 40 women diagnosed with GDM and 40 non-diabetic womenconstituted the study and control groups, respectively. Groups were compared for secondtrimester maternal serum resistin, visfatin and HbA1c levels, HOMA-IR and postpartum 75 gOGTT results.Results: Mean serum resistin (p¼ 0.071) and visfatin (p¼ 0.194) levels were similar betweenthe groups. However, mean BMI (p¼ 0.013), HOMA-IR (p¼ 0.019), HbA1c (p50.0001) andbirth weight (p¼ 0.037) were significantly higher in GDM group compared to controls.Type 2 diabetes and impaired glucose tolerance were detected in 2 (5%) and 7 (20%) womenin the GDM group, respectively, with 75 g OGTT performed at the postpartum 6th week.Resistin levels of patients with GDM and postpartum glucose intolerance were higher thanthose with GDM but no postpartum glucose intolerance (p¼ 0.012). Visfatin levels in the GDMgroup showed a positive correlation with biparietal diameter, head circumference, abdominalcircumference and femur length (p50.05).Conclusion: Maternal serum resistin and visfatin levels are unchanged in GDM. In patientswith GDM, second trimester resistin levels may be predictive for postpartum glucoseintolerance and second trimester visfatin levels may be related with fetal biometricmeasurements. Further larger studies are needed.

Keywords

Gestational diabetes, insulin resistance,resistin, visfatin

History

Received 4 August 2013Revised 23 November 2013Accepted 12 December 2013Published online 10 February 2014

Introduction

Gestational diabetes mellitus (GDM) is a disorder of thecarbohydrate metabolism first arising during pregnancy andcausing increased morbidity of both the fetus and the mother.GDM constitutes 90% of the diabetes cases during pregnancy [1].According to American Diabetes Association (ADA), its inci-dence changes between 1% and 14% and it complicates almost 7%of the pregnant patients, although the numbers can vary amongdifferent populations [2]. Furthermore, it is reported that 10–50%of the GDM cases develop type 2 diabetes in the postpartumperiod [3].

Various different hormones in the body like human placentallactogen (HPL), cortisol, growth hormone, estrogen, progesteroneas well as increased insulinase secretion from the placenta mayhave a role in the pathogenesis of GDM [4]. Besides being asource of energy, adipose tissue also acts as an endocrine tissue.Some novel molecules that are known to be secreted from theadipose tissue including tumor necrosis factor-alpha (TNF-a),

interleukin-6 (IL-6), resistin, visfatin, leptin are also keptresponsible from the pathogenesis of GDM [5]. Some adipocy-tokines like leptin, TNF-a, IL-6, resistin and visfatin havemetabolic and immunologic roles in obesity related inflammationand in progression to type 2 diabetes [6]. Resistin is a moleculethat resists to the activity of insulin and the circulating levelsof this molecule are increased in obese humans [7]. This pro-inflammatory molecule is reported to play role in the pathogen-esis of diabetes and diabetic complications [7]. The expressionof visfatin is also reported to increase in cases of abdominalobesity and type 2 diabetes [7,8].

Recent studies about the association of resistin and visfatinlevels with GDM have conflicting results. Some of them showthat cases with GDM have increased levels of resistin and visfatincompared to the control group [9,10], while others either reportno difference for these molecules between the two groups [11] orlower visfatin levels in the GDM group [12].

In this study, we aimed to investigate the association ofmaternal serum resistin and visfatin levels with GDM.

Materials and methods

This longitudinal cross-sectional study was carried out inObstetrics and Gynaecology Department of Duzce UniversitySchool of Medicine between January and July 2012. Duzce

Address for correspondence: Ahmet Karatas, Department of Obstetricsand Gynecology, Medical Faculty, Abant Izzet Baysal University, 14280Golkoy, Bolu, Turkey. Tel: +90 374 253 46 56. Fax: +90 374 253 46 15.E-mail: akaratas1973@hotmail.com

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University Non-Invasive Human Research Ethics Committeeapproved the study. Informed consent was obtained from allsubjects.

About 80 women with singleton pregnancies attending tothe obstetrics outpatient clinic for routine obstetric care wereincluded in the study. About 40 women diagnosed with GDM and40 non-diabetic women constituted the study and control groups,respectively. Screening for and diagnosis of GDM was performedby using 50 g glucose challenge test and 100 g oral glucosetolerance test (OGTT), respectively, between 24th and 28thgestational weeks. Groups were compared for maternal and fetaldemographic characteristics and maternal serum resistin, visfatin,HbA1c levels and HOMA-IR. Additionally, a 75-g OGTT wasperformed in women with GDM at the postpartum 6th week.Patients with a multiple pregnancy, pregestational diabetes,chronic medical diseases, collagen vascular diseases and chronicinflammatory diseases were excluded.

100 g OGTT

Patients with an abnormal 50 g glucose challenge test applied adiet lasting for 3 days and including an extra 150 g carbohydrate/day before the 100 g OGTT. The test was performed after 8 h offasting. Diagnosis of GDM after 100 g OGTT was made accordingto Carpenter and Couston criteria [13]. Patients with �2 abnormalvalues in the test were diagnosed to have GDM.

75 g OGTT

Patients with GDM underwent a 75-g OGTT after 8 h of fastingat the postpartum 6th week. Diagnosis of normal glucosetolerance (NGT), impaired glucose tolerance (IGT) and type 2DM was made according to ADA criteria [14].

Laboratory measurements

Fasting blood samples obtained from all patients to ethylenedia-minetetraacetic acid (EDTA) tubes to study resistin and visfatinlevels between the 24th and the 28th gestational weeks werecentrifuged and stored at �80� until being studied. Serum resistinand visfatin levels were measured by using specific ELISA kits(Bioscience [Quality, Inc, Austria] for resistin and Phoenix[Pharmaceuticals, Inc] for visfatin) and ELISA reader (Epoch,Biotek Inc).

Statistical analysis

Data were analyzed by using SPSS (Statistical Packages for theSocial Sciences) (ver. 16, Chicago, IL). Descriptive statisticswere expressed as mean ± SD, median (minimum-maximum) andnumber [percentage (%)], as appropriate. Independent samplest-test and Mann–Whitney U test was used to compare theparametric and non-parametric numeric data between the groups,respectively. Chi-squared test was used to compare the categoricalvariables between the groups. Covariance analysis was usedto compare the resistin and visfatin levels between the groups.To calculate the correlation coefficients of resistin and visfatinlevels with the numerical variables, Pearson or Spearmancorrelation analysis was used for the parametric and non-parametric data as appropriate. A p value 50.05 was consideredto be statistically significant.

Results

A total of 80 pregnant women (40 with GDM and 40 controls)were included in the study. Maternal demographic and biochem-ical parameters are demonstrated in Table 1. Mean age of the

Table 1. Comparison of maternal demographic characteristics and biochemical parameters, fetal ultrasonographic andpost-natal measurements in the control and gestational diabetes mellitus groups.

Control (n¼ 40)Mean ± SD M (min–max)

GDM (n¼ 40)Mean ± SD M (min–max) p

Age (year) 26.2 ± 4.5 30.1 ± 5.2 0.001Gravidity (n) 2 (1–7) 2 (1–6) 0.825Parity (n) 1 (0–3) 1 (0–4) 0.967Weight gain during pregnancy (kg) 13.4 ± 4.8 9 ± 4.9 0.001BMI (kg/m2)

Prepregnancy 23.7 ± 4.2 27.3 ± 4.4 0.001Pregnancy 27.1 ± 5.6 29.9 ± 4.3 0.013

100 g OGTT (mg/dl)1st hour – 198 ± 22.6 –

2nd hour – 166.5 ± 34.5 –3rd hour – 124.2 ± 33.7 –

Fasting glucose (mg/dl) 79 (54–123) 93 (67–203) 0.001Fasting insulin (mIU/ml) 7.02 (1.15–55.9) 12.8 (1.04–134.4) 0.043HOMA-IR 1.1 (0.09–11.06) 2.7 (0.09–41.1) 0.019HbA1c (%) 4.5 (4–5.1) 5.3 (4.4–7) 50.0001Resistin (pg/ml) 5301 ± 428 4177 ± 434 0.071Visfatin (ng/ml) 8.64 (3.19–20) 8.58 (3.3–20.32) 0.194Pregnancy week at run time 25.4 ± 1 25.7 ± 1 0.202Biparietal diameter (mm) 64 ± 3.4 65.5 ± 3.2 0.045Head circumference (mm) 237.7 ± 11.8 241.9 ± 12.3 0.132Abdominal circumference (mm) 214.8 ± 14.7 222.1 ± 16.8 0.044Femur length (mm) 47.6 ± 2.9 55.1 ± 3.8 0.426Estimated fetal weight (g) 843.3 ± 138 950.8 ± 181 0.002Amniotic fluid index (cm) 8,7 ± 1,4 9,8 ± 1,8 0.006Gestational age at delivery 37.6 ± 2.3 38.1 ± 1.5 0.262Delivery mode (Caesarean section); n (%) 23 (57.5) 26 (65) 0.508Birth weight (g) 3061 ± 574 3357 ± 595 0.037Large for gestational age; n (%) – 3 (7.5) 0.241

GDM, gestational diabetes mellitus; Mean ± SD, Mean ± standard deviation; M (min–max), median (minimum–maximum);n (%): number (%); BMI, body mass index.

356 A. Karatas et al. Gynecol Endocrinol, 2014; 30(5): 355–358

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patients, prepregnancy and pregnancy body mass index (BMI)values were higher and weight gain during pregnancy was lowerin GDM group than that of the control group (p50.05 for all)(Table 1) Maternal serum resistin and visfatin levels in the GDMgroup was lower than that of the control group, but the differencewas not statistically significant.

Information about ultrasound findings and delivery recordsof the patients are demonstrated in Table 1. Gestational age at theultrasound date and at delivery, mode of delivery and numberof large for gestational age (LGA) infants were similar in the twogroups. Biparietal diameter (BPD), fetal abdominal circumference(AC), estimated fetal weight, amniotic fluid index and birthweight were higher in the GDM group (p50.05 for all) (Table 1).There were three large for gestational age (LGA) infants in theGDM group. Within the GDM group, when patients with andwithout LGA infants were compared, maternal serum resistinlevels (3759.1 ± 2784.5 and 4020 ± 2496.9 pg/ml) and maternalserum visfatin levels (9.6 ± 3.9 and 11.1 ± 3.1 ng/ml) were foundto be similar (p¼ 0.864 and p¼ 0.519), respectively.

Correlation analysis of BMI, BPD, head circumference (HC),femur length (FL), AC and birth weight with resistin in bothgroups showed that, among these parameters tested, there wasonly a moderate degree of positive correlation between maternalresistin levels and birthweight in the control group (Spearmanr¼ 0.491, p¼ 0.003). Correlation analysis of visfatin with thesame parameters showed no significant correlation in the controlgroup. However, in the GDM group, visfatin level was positivelycorrelated with BMI, BPD, HC, AC, FL, but not with birthweight(Table 2).

At the postpartum 6th week, 34 of the 40 GDM casesreadmitted for a follow-up visit. About 75 g OGTT performed atthis visit resulted in a diagnosis of NGT in 25 (75%) of the cases,IGT in 7 (17.55) of the cases and type 2 diabetes in 2 (5%) of thecases. During statistical analysis, two cases with type 2 diabeteswere evaluated in the same group with IGT. Fasting and 2nd hourglucose values in the NGT group were significantly lowerthan that of the IGT group (p50.05 for both, Table 3). Secondtrimester maternal serum visfatin levels were similar in both

groups, however, maternal serum resistin levels in the IGT groupwere significantly higher than that of the NGT group (p50.05,Table 3).

Discussion

In this study, we found that pregnant women with and withoutGDM had similar second trimester serum resistin and visfatinlevels. However, patients with GDM who also had postpartumIGT had significantly higher second trimester levels of serumresistin than those who had postpartum NGT. Second trimesterserum visfatin levels of women with GDM showed a positivecorrelation with BMI, BPD, HC, AC, FL but not with birthweight.Second trimester serum resistin levels of women without GDMshowed a positive correlation with birthweight.

It is known that plasma resistin levels are higher in pregnantpatients when compared to non-pregnants [15]. Kuzmicki et al.[16] reported that pregnant patients with GDM had significantlyhigher levels of resistin than those with a NGT, while otherstudies reported no difference between the resistin levels ofpregnant patients with or without GDM [11,17]. There is no clearevidence about the relationship of GDM with visfatin. Telejkoet al. [18] reported that serum visfatin levels in cases with GDMwere similar to the control group. Additionally, they reported aninverse relationship between HbA1c and visfatin levels in patientswith GDM. Rezvan et al. [12] reported lower serum visfatin levelsin the control group. They found no association between serumvisfatin levels and maternal age, BMI, nutritional status butreported a positive correlation with the HbA1c levels. Skvarcaet al. [10] investigated the adipocytokines in pregnant women atdifferent insulin resistance levels including NGT, IGT and GDMgroups. They found no statistically significant between-groupdifferences in serum resistin and visfatin concentrations. Theymentioned that these adipocytokines were not adequately sensi-tive to replace HOMA-IR in pregnancy.

In this study, we also found that the resistin and visfatin levelsof pregnant women with and without GDM were similar.Actually, both adipokines seemed to be lower in the GDMgroup than the control group but the difference was notstatistically significant. Finding lower levels of these adipokinesin the GDM group contradicts the previous reports [12,16].But our finding that GDM patients with postpartum IGT hadhigher second trimester levels of serum resistin than those withpostpartum NGT is in accordance to the literature. Because,we know that resistin acts in the opposite direction to insulinand plays a role in the pathogenesis of diabetes [7]. This findingsuggests that second trimester resistin levels in patients withGDM may have a predictive role for postpartum glucoseintolerance if this finding is supported in further studies.

Fetal macrosomia is frequent among patients with GDM andthis causes an increase in perinatal complications. Several studiesin the literature have investigated the presence of any associationbetween birthweight and adipokines [19–21]. Wang et al. [20]reported a negative correlation between umbilical serum levelsand placental expression of resistin with birthweight. Similarly,Shang et al. [21] reported that maternal serum visfatin levels werelower in the macrosomic fetuses than in fetuses with growthrestriction and concluded that levels of visfatin could affectintrauterine growth. Mohamed et al. [22] evaluated the resistinlevels in the cord blood of the term newborns of the diabeticmothers and found that resistin levels were lower compared tothe control group. They reported that the glucose, insulin andresistin levels of the macrosomic and normal weight fetuses of thediabetic mothers were similar [22]. Decrease or increasein visfatin levels in pregnant patients with GDM is reported tobe associated with fetal growth [23,24]. In our study, the

Table 3. Comparison of fasting and 2-h glucose levels of normal glucosetolerance and impaired glucose tolerance groups according to the resultsof 75 g OGTT at postpartum sixth week and second trimester maternalserum resistin and visfatin levels in gestational diabetes mellitus group.

NGT (n¼ 25)Mean ± SD

IGT (n¼ 9)Mean ± SD p

75 g OGTT (mg/dl)Fasting 87.2 ± 10.7 97.2 ± 12.3 0.0292nd hour 108.5 ± 13.6 181.5 ± 40.9 0.001Resistin (pg/ml) 3463 ± 2501 5835 ± 1522 0.012Visfatin (ng/ml) 9.5 ± 3.6 9.6 ± 4.8 0.915

NGT, normal glucose tolerance; IGT, impaired glucose tolerance;mean ± SD, mean ± standard deviation.

Table 2. Correlation coefficients of maternal serum visfatin levels withbody mass index, biparietal diameter, head circumference, abdominalcircumference and femur length in gestational diabetes mellitus group.

Visfatin (ng/ml)

GDM Correlation coefficient (r) p

Body mass index (kg/m2) 0.491 (Pearson r) 0.001Biparietal diameter (mm) 0.368 (Pearson r) 0.019Head circumference (mm) 0.527 (Spearman r) 50.001Abdominal circumference (mm) 0.380 (Spearman r) 0.016Femur length (mm) 0.412 (Spearman r) 0.008

DOI: 10.3109/09513590.2014.887670 Resistin and visfatin in GDM 357

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mean birthweight was significantly higher in the GDM groupwhich included three LGA infants. Within the GDM group, serumresistin levels of patients with and without LGA infants weresimilar, in accordance to the finding of Mohamed et al. [22].In contrast to the previous studies which reported a negativecorrelation between resistin level and birthweight [20], wedetected a positive correlation between resistin level and birthweight in the control group (r:0.450, p:0.007), but, not in theGDM group. An important finding of our study was the positivecorrelation observed between visfatin level and the fetal biometricmeasurements in the GDM group. In the light of this finding,we can think that higher visfatin levels in the second trimester inpatients with GDM may be an indicator of hyperglycemia inducedaccelerated fetal growth. But further well designed larger studiesare needed about this issue.

Early detection of GDM and prevention of related perinatalcomplications is important. To assess the association of maternalvisfatin levels and GDM in early gestational weeks, Ferreira et al.[25] evaluated the serum levels of 400 pregnant patients between11 and 13 weeks of gestation. During follow up, 100 of thesepatients developed GDM while 300 did not. Serum visfatin levelsof patients that developed GDM during follow-up was reported tobe higher than that of the control group. It was shown thatmaternal visfatin concentration changes as a function of gesta-tional age with a different pattern in normal and overweightpregnant women [23]. We had no data about the first trimestervisfatin levels of our patients, but the second trimester visfatinlevels of patients with and without GDM in our study weresimilar. It is reported that visfatin secretion is higher in obesepatient [26]. In our study, we found a positive correlation betweenserum visfatin levels and maternal BMI, in accordance with theliterature.

Limitations

The small sample size and assessment of maternal serum resistinand visfatin levels only in second trimester are the limitationsof our study. We suggest that longitudinal observation on theprofile of these hormones during pregnancy and postpartumperiod would enhance our insight into the relationship ofadipokines with the pathogenesis of GDM.

Conclusion

Maternal serum resistin and visfatin levels were found to beunchanged in patients with GDM although the GDM group had ahigher BMI than the control group. Patients with GDM withhigher second trimester resistin levels may be at higher risk todevelop postpartum glucose intolerance. Visfatin levels in thesecond trimester may be associated with the rate of fetal growth inpatients with GDM. Further larger prospective studies are needed.

Acknowledgements

The authors thank obstetrics and gynecology clinic employees for theircontributions to the study.

Declaration of interest

The authors report no declarations of interest. This study was financiallyendorsed by Duzce University, Medical Faculty Scientific Study ResearchCommission (registration number 2012.04.HD.060).

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