The Effect of Chromium in The Pathogenesis of Insulin Resistance in Preeclampsia

Haydar Hashim Al-Shalah
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Keywords : Preeclampsia, Chromium, Insulin resistance, HOMA, Fasting plasma glucose
Medical Journal of Babylon  13:3 , 2016 doi:1812-156X-13-3
Published :25 December 2016

Abstract

Insulin resistance is well established to be related with preeclampsia. The action of insulin in human appears to be potentiated by chromium. The aim of present study was assessment of chromium level in the development of insulin resistance in preeclampsia and hence its pathogenesis . This case control study was achieved on subjects recruited from Babylon Teaching Hospital for Obstetric & Gynecology during the period between September 2013 till October 2015, included 90 pregnant women, 45 of them identified with preeclampsia in the third trimester and other 45 were apparently healthy pregnant women taken as a controls. Chromium concentrations was measured by Atomic Absorption Spectrophotometry. Fasting insulin was estimated by Enzyme Linked Flouroscent Immune-Assay (ELFA) technique and fasting plasma glucose concentration by glucose oxidase method. Insulin resistance was calculated by homeostatic model assessment(HOMA)using mathematical equation. The results of present study showed no significant difference in fasting plasma glucose concentrations between patients and controls (P value >0.05),while there were a significant differences in chromium concentration level and insulin resistance between two groups (P value <0.05).However, there was no correlation between insulin resistance in patients with preeclampsia and low chromium level (r= 0.101, p=0.508). The present study concluded that low chromium level has no impact on the development of insulin resistance in preeclampsia.

Introduction

Preeclampsia (PE) is characterized by hypertension and proteinuria occurring after the twentieth week of gestation in a previously normotensive woman and completely disappear by the sixth postpartum week[1]. Complications ofPE and accompanied pathologies have become one of the most important causes of maternal and fetal morbidity and mortality in the world, leading toabout 40% of births delivered before 35 weeks of gestation. Furthermore, PE has been strongly related to an increased risk of later-life death due to cardiovascular disease, independent of other risk factors. The incidence of PE is around 5–10% of all pregnant women worldwide and despite the amount of resources spent in the research and treatment of this pathology, its development is still barely predictable and thus challenging to prevent and manage clinically[2]. The physio-pathological process of PE starts with inadequate trophoblast invasion early in pregnancy, which causes an increase in oxidative stress leading to the development of systemic endothelial dysfunction in the later phases of the disease, and consequently to the characteristic clinical manifestation of PE, with hypertension, proteinuria, and edema[3]. Increased insulin resistance (IR) is well established to be related with PE. There are several opinions to demonstrate this relationship. Elevated insulin increases sympathetic tone and muscle blood flow and also in chronic conditions (unlikely relevant to PE ) increases vascular smooth muscle growth. IR is likely to be involved in the pathogenesis of PE rather than being caused by PE[4]. Increased IR can stimulate the sympathetic nervous system and cause an increase in expression of receptors for endothelin, both of which events lead to increased blood pressure. Hyper-insulinemia can also producehypertri-glyceridemia, leading to endothelial dysfunction and decrease production of prostacyclin . This hyperinsulinemia can remain for as long as 17 years after preeclamptic pregnancy and may contribute to a woman s increased risk of cardiovascular disease[5,6]. Chromium (Cr) is an elementoccurred naturally in animals, plants, rocks, and soil. It can present in several entities . The most common are Cr (0), Cr(III), and Cr (VI), which is also known as hexavalent Cr[7]. The main biological role of Cr inhuman appears to potentiate the action of insulin, aspart of a low molecular weight chromium binding substance(chromodulin). Cr may also be importantin gene expression, lipoprotein metabolism and in maintainingnucleic acid structure[8,9]. The aim of this study was to assess the role ofCr level in the development of IR in PE and henceits pathogenesis.

Materials and methods

This case control study was achieved on subjects recruited from Babylon Teaching Hospital for Obstetrics & Gynaecology, City of Hilla. Samples were obtained during the period between September 2013 till October 2015, included 90 pregnant women, 45 of them identified  with PE by gynecologist expert in the third trimester and other 45  were apparently healthy pregnant women taken as a controls in the same period of pregnancy.
Complete evaluation of pregnant women was undertaken which involve history, physical examination, laboratory investigations, and  ultrasound. Pregnant women  more than 40 years old, body mass index > 30, smoking, prior history of PE,family history of PE, prior hypertension or kidney disease, previous history of vascular disease, and multiple pregnancy were excluded from this study .
The anthropometric measurementsinvolving age, gestational age, and body mass index of PE group were comparable  to control group, where there wasno significant differences (P> 0.05).
 
Ethical considerations
Acceptance of scientific committee of the Clinical Biochemistry Department/College of Medicine/University of Babylon  and permissionof Babylon Health Directorate/Ministry of Health & Information Center for Research & Development of Babylon Province/Iraq were taken.
The aims were informed to all contributors involved in this study and verbal consent had been taken.
Samples collection
Venous blood samples were aspirated from studied group after 5 hours fast. Five ml of blood were obtained from each subjects by vein puncture , put in heparin containing tube, then centrifuged at 2000×g for approximately 5 minutes. plasma was used for measurement of fasting plasma glucose (FPG), fasting insulin (FI) level and Cr concentration.
Determination of chromium, fasting plasma glucose and fasting insulin  Concs:
Cr concentrationswas estimated by  Furnace Graphite Atomic Absorption Spectrometer provided by PG Instruments Ltd (United Kingdom)with usage of Cr hollow cathode lamps supplied by Varian.
FPG concentration was estimated by glucose oxidase method using a kit provided by Biolabo/France.
FIwas determined by Enzyme linked Flouroscent Immune-Assay (ELFA) using AIA-360 Automated Immunoassay Analyzer from  Tosoh Bioscience/Japan.
IR was calculated by HOMA-IR model using mathematical equation[10].

Fasting insulin(mIU/ml) x Fasting plasmaglucose (mmol/L
HOMA-IR=  
22.5
Statistical Analysis
 Statistical analysis was achieved  by using statistical package for social sciences (SPSS) 20th version. Quantitative data were presented as mean ± SD and independent sample t-test was used to compare between two groups. Chi square (X2) test was used to find the significance of the categorical variables and Pearson’s correlation was used to establish the relationships between variables .P-value of < 0.05was considered to be statistically significant.




Results

Several studies have investigated the role of IR in development of PE. In this study, we investigated whether PE is associated with plasma Cr level and whether it is a subsequent element for PE as it is an essential nutrient for the maintenance of normal glucose tolerance and its deficiency causes IR as presented by Ayling RM and Hua Y et al [8,11]. Table (1) showed no significant difference in FPG between patients and controls ,P value >0.05(both preeclamptic and normotensive women were able to dispose glucose equally) which may be attributed to significant difference in FI level as it is higher in patients rather than controls to compensate the significant higher IRpresented in the same table for patients to alleviate glucose level. This finding agreed with the definition of compensatory hyperinsulinaemia presented in the review of Wilcox G [12] as it is occurs when pancreatic ? cell secretion increases to maintain normal blood glucose levels in the setting of peripheral IR in muscle and adipose tissue.This response is consistent also with a pregnancy-induced state of peripheral IR, the purpose of which is likely to ensure a sustained postprandial supply of glucose to the fetus as reported by Hauth JC[5]. Table (1)also showed a significant low Cr plasma level in patient group compared to control as it is a potential contributor to IR as presented by Hua Y et al [11], Wilcox G [12], AndersonRA [13] and Vladeva SV et al [14].

Discussions

Several studies have investigated the role of IR in development of PE. In this study, we investigated whether PE is associated with plasma Cr level and whether it is a subsequent element for PE as it is an essential nutrient for the maintenance of normal glucose tolerance and its deficiency causes IR as presented by Ayling RM and Hua Y et al [8,11]. Table (1) showed no significant difference in FPG between patients and controls ,P value >0.05(both preeclamptic and normotensive women were able to dispose glucose equally) which may be attributed to significant difference in FI level as it is higher in patients rather than controls to compensate the significant higher IRpresented in the same table for patients to alleviate glucose level. This finding agreed with the definition of compensatory hyperinsulinaemia presented in the review of Wilcox G [12] as it is occurs when pancreatic ? cell secretion increases to maintain normal blood glucose levels in the setting of peripheral IR in muscle and adipose tissue.This response is consistent also with a pregnancy-induced state of peripheral IR, the purpose of which is likely to ensure a sustained postprandial supply of glucose to the fetus as reported by Hauth JC[5]. Table (1)also showed a significant low Cr plasma level in patient group compared to control as it is a potential contributor to IR as presented by Hua Y et al [11], Wilcox G [12], AndersonRA [13] and Vladeva SV et al [14].

Conclusions

Low chromium level has no effect on the development of insulin resistance in preeclampsia.

References

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