|Year : 2018 | Volume
| Issue : 2 | Page : 229-234
Adiponectin levels in serum of women with pre-eclampsia
Mohamed K Aloush1, Mohamed F Elsherbiny1, Tamer M Asar1, Hisham A Essa2, Alshaimaa H Mohamed3
1 Gynecology and obest’atric Department, Benha Faculty of Medicine, Benha University, Egypt
2 Clinical and Chemical Pathology Department, Benha Faculty of Medicine, Benha University, Egypt
3 Ministry of Health, Qalubyia Province. Gyn. & Obst., Egypt
|Date of Submission||28-Jan-2018|
|Date of Acceptance||19-Mar-2018|
|Date of Web Publication||17-Aug-2018|
Dr. Alshaimaa H Mohamed
Faculty of Medicine, Benha University, Benha, 13511
Source of Support: None, Conflict of Interest: None
Background and aim The aim of this study was to investigate the association between serum adiponectin levels and some clinical and hormonal parameters in cases of pre-eclampsia.
Patients and methods This cross-sectional controlled observational study was carried out on 75 pregnant women recruited from antenatal outpatient clinic and obstetric departments of Benha University Hospital. The women were subdivided into three subgroups: 25 normal pregnant women, 25 pregnant women with mild pre-eclampsia, and 25 pregnant women with severe pre-eclampsia. All studied groups were subjected to complete history taking, clinical examination, and routine laboratory investigations, for example, complete blood count, Rh, random blood sugar, serum uric acid and proteinuria, serum adiponectin, progesterone, and estradiol levels.
Results Serum adiponectin levels in women with pre-eclampsia were significantly higher than in normal pregnant women, and the increase was more marked in cases of severe pre-eclampsia. There was a significant positive correlation between adiponectin levels and arterial blood pressure in all groups. However, there was no correlation between serum adiponectin and estradiol and progesterone levels. The results support the theory that adiponectin might be part of a feedback mechanism for improving insulin sensitivity and cardiovascular health in patients with pre-eclampsia.
Conclusion It has been concluded from the study that plasma adiponectin level is increased in pre-eclampsia. It can be taken independently or along with other parameters as a marker for severity of pre-eclampsia, hence, avoiding risk effects of pre-eclampsia to mother and fetus. Serum adiponectin assay increases sensitivity for prediction of pre-eclampsia.
Keywords: adiponectin, BMI, estradiol, pre-eclampsia, progesterone, systolic blood pressure and diastolic blood pressure
|How to cite this article:|
Aloush MK, Elsherbiny MF, Asar TM, Essa HA, Mohamed AH. Adiponectin levels in serum of women with pre-eclampsia. Benha Med J 2018;35:229-34
|How to cite this URL:|
Aloush MK, Elsherbiny MF, Asar TM, Essa HA, Mohamed AH. Adiponectin levels in serum of women with pre-eclampsia. Benha Med J [serial online] 2018 [cited 2018 Dec 13];35:229-34. Available from: http://www.bmfj.eg.net/text.asp?2018/35/2/229/239183
| Introduction|| |
Hypertensive disorders complicate 5–10% of all pregnancies. It forms one of the members of the deadly triad with hemorrhage and infection . Pre-eclampsia is described as pregnancy-specific syndrome that can affect virtually every organ system. Although pre-eclampsia is much more than simply gestational hypertension with proteinuria, proteinuria remains an important objective diagnostic criterion . Adiponectin is an adipocyte-derived plasma protein that is believed to be involved in the regulation of insulin resistance and glucose homeostasis .
The basic pathological changes of pregnancy-induced hypertension and eclampsia involve extensive vascular endothelial cell injury, vascular spasms, decreased glomerular filtration, and increased vascular permeability, resulting in persistent hypertension and proteinuria .
Experimental and clinical studies have indicated that low plasma levels of adiponectin are associated with obesity-related metabolic and vascular diseases, both of which are risk factors for pre-eclampsia. Insulin resistance is a hallmark of pregnancy that peaks in the third trimester. Moreover, this insulin resistance is increased in pregnancies complicated with pre-eclampsia. The evidence that adiponectin interacts with many risk factors of pre-eclampsia, for example, insulin resistance, inflammatory disorders, and abnormal vascular reactivity , suggests that adiponectin may play a role in the syndrome.
Adiponectin is a 30 kda protein that is synthesized almost exclusively by adipocytes. It exists in three major oligomeric forms: a low-molecular-weight trimer, a middle-molecular-weight hexamer, and high-molecular-weight 12- to 18-mers adiponectin .
Several mechanisms to explain the elevation of adiponectin levels in pre-eclampsia have been proposed. It may be secondary to exaggerated nonspecific adipocyte lipolysis or a physiological response to enhance fat utilization and attenuated endothelial damage . Other factors that may cause the elevation of plasma adiponectin concentrations in pre-eclampsia include adiponectin resistance , alterations in renal function, and ongoing adiponectin synthesis in adipose tissue . Placental secretion of adipocytokines is another important factor influencing their concentrations in maternal blood. Tumor necrosis factor (TNF)-α, a principal adipocytokine, as well as TNF receptors, is expressed in normal and pre-eclamptic placenta.
Recently, adiponectin was found to suppress TNF-α-mediated expression of endothelial adhesion molecules in response to inflammatory stimuli , suggesting that adiponectin may act as an inhibitor of the inflammatory cytokine network.
| Patients and methods|| |
This cross-sectional controlled observational study was carried out on 75 pregnant women recruited from antenatal outpatient clinic and obstetric departments of Benha University Hospital in period from October 2014 to October 2017. The study was approved by the Research Ethical Committee and an informed consent was obtained from each participant before enrollment in the study.
Women targeted were of 18–30 years old, with single pregnancy, and 24 weeks or more of gestational age. Consent was obtained from each patient after full explanation of the objectives and procedures of the study. Women included in this study were divided into the following groups: normal pregnancy (n=25), mild pre-eclampsia (n=25), and severe pre-eclampsia (n=25). The normal pregnancy (n=25) and mild pre-eclampsia groups had no medical disorders and normal routine laboratory investigation findings. Patients were defined according to criteria established by the Royal College of Obstetricians and Gynaecologists . All women in the normal group were healthy, normotensive, and had single gestation. Mild pre-eclampsia was systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg on two occasions at least 6 h apart, typically occurring after 20 weeks of gestation (no more than 1 week apart) in conjunction with proteinuria of 300 mg/24 h urine collection or more than 1+ on two random sample urine dipsticks at least 6 h apart (no more than 1 week apart) . Severe pre-eclampsia was persistent SBP more than 170 mmHg on two occasions or DBP more than 110 mmHg on two occasions, together with significant proteinuria (≥1 g/l). Clinical features of severe pre-eclampsia (in addition to hypertension and proteinuria) were symptoms of severe headache, liver tenderness, visual disturbance, platelet count falling to below 100×103/µl, epigastric pain and/or vomiting, abnormal liver enzymes (aspartamine or alanine aminotransferase rising to above 70 IU/l), signs of clonus, HELLP syndrome (hemolytic anemia/elevated liver enzymes/low platelet count), and papilledema.
Patients with systemic diseases such as essential hypertension, diabetes mellitus, anemia, renal diseases, endocrine disorders, autoimmune diseases such as systemic lupus erythematous, and grand multiparity were excluded.
In all subjects, fasting blood was drawn after 8 h of fasting. In the pre-eclamptic group, blood samples were collected when the patient presented for evaluation and before initiation of medical therapy. In all patients, plasma adiponectin levels were measured by enzyme–linked immunosorbent assay (ELISA) according to Arita et al. .
Serum estradiol levels were measured according to Tietz  and serum progesterone level according to Tietz . Samples were taken into standard serum tubes, allowed to clot, and then serum was separated by centrifugation and stored at −60°C until assayed.
The yielded data were collected and analyzed using IBM SPSS version 10 (SPSS Inc., Chicago, Illinois,USA) software package. Both descriptive and inferential statistics were used. Moreover, tabular and diagrammatic presentations were used. Analysis of variance test was used for quantitative variables, whereas χ2-test was used for nominal qualitative variables. The minimum accepted level of significance was 0.95 (P≤0.05) in all study phases. Results are tabulated and statistically analyzed using computer programs Microsoft Excel, version 7 and suitable program.
| Results|| |
[Table 1] shows the serum adiponectin levels in the three study groups. In the women with mild and severe pre-eclampsia, the mean serum adiponectin levels [20.12 (SD 3.1) µg/ml and 23.1 (SD 2.7) µg/ml, respectively] were significantly higher than that of normal pregnant women [9.2 (SD 2.4) µg/ml] (P<0.001).
[Table 2] shows the BMI of the three studied groups. The mean values of BMI in the women with normal pregnancy, mild pre-eclampsia, and severe pre-eclampsia [28.6 (SD 2.3) kg/m2, 30.3 (SD 2.6) kg/m2, and 30.7 (SD 2.5) kg/m2, respectively] showed significant difference between the groups (P<0.05).
[Table 3] shows the serum levels of estradiol and progesterone in the three studied groups. There were no significant differences in estradiol levels among the groups; the mean values in normal pregnancy, mild pre-eclampsia, and severe pre-eclampsia were 32.9 (SD 5.4) ng/ml, 34.3 (SD 5.6) ng/ml, and 35.4 (SD 4.1) ng/ml, respectively (P>0.05). There were also no significant differences in progesterone levels among the groups; the mean values were 110 (SD 10.4) ng/ml, 111.8 (SD 10.1) ng/ml, and 111.6 (SD 10.3) ng/ml in normal pregnancy, mild pre-eclampsia, and severe pre-eclampsia groups, respectively (P>0.05) ([Table 4]).
|Table 3 Serum estradiol and progesterone levels in the three study groups|
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Regarding relation of serum adiponectin to different clinical variables, there was a significant positive correlation relationship with all the clinical variables in the three groups ([Table 5],[Table 6],[Table 7]).
| Discussion|| |
Pre-eclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks of gestation and can present as late as 4–6 weeks postpartum. It is clinically defined by hypertension and proteinuria, with or without pathologic edema .
Adiponectin (also referred to as adipoq, Acrp30 and adipocyte complement-related protein) is a 30 kda protein that is synthesized almost exclusively by adipocytes . Adiponectin is considered an insulin-sensitizing, anti-inflammatory, and antiatherogenic adipokine. It stimulates glucose uptake in skeletal muscle and reduces hepatic glucose production through AMP-activated protein kinase .
This study was conducted at Benha University Hospital. The study included 75 pregnant women at 24–40 weeks of pregnancy. These women were categorized into three groups according to the results: group 1 included 25 women with normal pregnancy, group 2 included 25 pregnant women with mild pre-eclampsia, and group 3 included 25 pregnant women with severe pre-eclampsia.
Regarding maternal age, gestational age, gravidity, serum estradiol, and serum progesterone in normal control and study groups, the comparison revealed statistically insignificant difference (P>0.05).
In this study, regarding SBP, the mean value of SBP in control group was 108±8.5. The mean value of SBP in the study group 1 was 150±5.3 and the mean value of SBP in the study group 3 was 169±5.0. The comparison revealed statistically significant difference (P<0.001). Regarding DBP, the mean value of DBP in control group 1 was 72.6±7.8, in group 2 was 94.5±2.5, and in the group 3 was 111.0±5.0. The comparison revealed statistically significant difference (P<0.001).
In this study, the mean value of adiponectin level in group 1 (control group) was 9.2±2.4, in group 2 (study group) was 20.12±3.1, and in group 3 (study group) was 23.1±2.7. So when comparing the serum adiponectin levels between control group and study groups, there was a highly statistically significant difference between the control group and study groups (P<0.001).
The results revealed that serum adiponectin levels were significantly higher in the women with pre-eclampsia in comparison with normal pregnant women who had similar gestational age. The difference was more marked in cases of severe pre-eclampsia than of mild pre-eclampsia. However, there were no significant differences between the groups in either serum estradiol or progesterone levels.
The results are also in line with the findings of D’Anna et al.  who reported increases in the levels of adiponectin during the third trimester in patients with pre-eclampsia.
Serum adiponectin levels did not correlate with estradiol or progesterone levels in any group. In contrast, there was a significant positive correlation between serum levels of adiponectin and both systolic and DBPs in the pre-eclamptic group. It is reported that the second half of pregnancy is a state of physiological insulin resistance, which is characterized by hyperinsulinemia, glucose intolerance, and lipid abnormalities .
This state of insulin resistance is exacerbated in pre-eclampsia, together with enhanced systemic inflammatory reactivity and endothelial dysfunction. At the same time, the circulating levels of both adiponectin and leptin are elevated in pre-eclampsia with the enhancement of insulin sensitivity .
When the pathological characteristics of pre-eclampsia and the changes in adiponectin and leptin levels are considered together, it is clear that the elevation of serum adiponectin and leptin is paradoxical and may play an important role in the pathophysiology of pre-eclampsia. This concept was supported by Fasshauer et al. , who reported increased serum levels of adiponectin in patients with pre-eclampsia which were positively associated with markers of insulin sensitivity in those patients. They concluded that adiponectin might be part of a physiological feedback mechanism improving insulin sensitivity and cardiovascular health in patients with pre-eclampsia . In this study, serum adiponectin levels showed a significant positive correlation with both systolic and DBPs in all groups. This finding is in line with that of Li and colleagues who reported a positive correlation between adiponectin and blood pressure in normotensive populations. Moreover, Ouchi and colleagues concluded that this effect may be mediated via inflammatory pathway or lipid metabolism. Adiponectin has been shown to have proangiogenic, antiatherogenic, and anti-inflammatory functions in the endothelium .
Moreover, hypoadiponectinemia is associated with impaired endothelium-dependent vasodilatation and reduced blood flow , whereas it is not considered as a risk factor for hypertension. These data suggest that adiponectin might maintain endothelial function, and its deficiency might lead to endothelial dysfunction/hypertension. Thus, the elevation of circulating adiponectin might be a physiological response to the endothelial dysfunction caused by angiogenic factors derived from the placenta in women with pre-eclampsia. Taken together, these findings indicate that adiponectin has a role, either direct or indirect, in the regulation and integrity of the vascular system.
In contrast, our results contradict those of other investigators who reported decreased adiponectin levels in women with pre-eclampsia in comparison with normotensive pregnant women; they also suggested that this decrease may contribute to the pathophysiology of pre-eclampsia .
Ouyang et al.  found reduced adiponectin levels in women with pre-eclampsia, especially in severe cases. This contradiction may relate to differences in body fat, insulin sensitivity, or hemoconcentration in the study populations.
| Conclusion|| |
Adiponectin was markedly increased in case of pre-eclampsia, especially in severe cases, and there was a positive correlation between adiponectin levels and blood pressure, but no correlation between adiponectin levels and estradiol or progesterone levels. From a preventive and therapeutic perspective, understanding the mechanisms involved in the regulation of adiponectin levels in pre-eclampsia may allow the design of a new class of agents to combat many risk factors in this disease, such as hypertension and endothelial dysfunction.
The current study was done to compare and confirm the reported increase in pre-eclampsia and to investigate the possibility of serum adiponectin being a predictor of severity of pre-eclampsia.
The results of this study are in agreements with the study done by Lu et al. . This study was carried out to determine the changes in serum levels of adiponectin, leptin, soluble leptin receptor, and the free leptin index in women with pre-eclampsia. Blood samples were collected from 38 pregnant women with pre-eclampsia and 42 from normotensive pregnant women as controls. Serum concentrations of adiponectin and leptin level were determined by enzyme-link immunosorbent assay. No significant differences were observed between the groups regarding maternal age and gestational age. Women with pre-eclampsia had significantly higher levels of serum adiponectin and leptin levels, and a higher free leptin index than controls (P<0.01, <0.001 and <0.001, respectively). There were no significant differences between the two groups in serum levels of soluble leptin receptor (P>0.05). In this study, serum adiponectin was done in addition to leptin .
In this study, when control was taken into account, there was no statistically significant correlation between age and adiponectin parameters (P>0.05). However, a statistically highly significant correlation was observed between SBP, DBP, and adiponectin level in pregnancies complicated with pre-eclampsia (P<0.001).
Serum adiponectin level and other parameters were measured in every group. All data were tabulated, statistically, and analyzed by statistical program for social science. The level of significance was P value less than 0.002.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]