Assessment of insulin resistant and the related cardio-metabolic factors in overweight-obese women presented with missed abortion, Baghdad, Iraq

Abdulzahra N. M. Al-Shareefi; Marwan S. M. Al-Nimer; Henan D. S. Aljebory; Bushra T Hasan

doi:10.4103/2347-2618.171961

ORIGINAL ARTICLE

Year : 2015 | Volume : 3 | Issue : 2 | Page : 66-71

Assessment of insulin resistant and the related cardio-metabolic factors in overweight-obese women presented with missed abortion, Baghdad, Iraq

Abdulzahra N. M. Al-Shareefi¹, Marwan S. M. Al-Nimer², Henan D. S. Aljebory¹, Bushra T Hasan³
¹ Department of Obstetrics and Gynecology, Al-Mustansiriya University, Baghdad, Iraq
² Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq
³ Department of Obstetrics and Gynecology, Al-Yarmouk Teaching Hospital, Baghdad, Iraq

Date of Web Publication

16-Dec-2015

Correspondence Address:
Marwan S. M. Al-Nimer
College of Medicine, Al Mustansiriya University, Baghdad
Iraq

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2347-2618.171961

Abstract

Aims: This study aimed to assess the status of insulin resistance (IR) in overweight-obese women presented with missed abortion and to look for the presence of other cardio-metabolic risk factors. Setting and Design: This observational study was carried at Al-Yarmouk Teaching Hospital in Baghdad, Iraq during the period from March 1, 2014, to January 31, 2015. Materials and Methods: A total number of 60 patients presented with missed miscarriage and managed with misoprostol and, dilatation and curettage (D and C) were enrolled in the study. The data of anthropometric and blood pressure were collected. Fasting serum lipid profile, serum glucose, and fasting insulin were determined. IR is assessed by using the homeostatic model assessment-IR (HOMA-IR). The patients were grouped according to the body mass index (BMI) into Group I (BMI <25 kg/m ² ) and Group II (BMI ≥25 kg/m ² ). Results: There is the nonsignificant difference between Group I and Group II in the characteristics and the clinical presentations of the patients. Significant high percent of the history of missed miscarriage observed in Group II compared with Group I (35.6% vs. 6.7%, respectively). Group II women significantly needed D and C intervention in addition to misoprostol therapy compared with Group I (75.6% vs. 13.3%) respectively. Although the blood pressure and lipid profile determinants are within normal levels, they significantly higher in Group II compared with Group I. Fasting serum insulin levels and HOMA-IR index are significantly higher in Group II (13.0 ± 0.5 μU/ml and 2.75 ± 0.5 μU/ml) than Group I (12.2 ± 0.3 μU/ml and 2.43 ± 0.11 μU/ml), respectively. Conclusion: Miscarriage overweight-obese women have significant IR as well as alteration in metabolic determinants. Misoprostol per se is not enough to produce spontaneous expulsion of the uterine content and surgical intervention is needed in these women.

Keywords: Insulin resistance, missed abortion, obesity

How to cite this article:
Al-Shareefi AN, Al-Nimer MS, Aljebory HD, Hasan BT. Assessment of insulin resistant and the related cardio-metabolic factors in overweight-obese women presented with missed abortion, Baghdad, Iraq. Saudi J Obesity 2015;3:66-71

How to cite this URL:
Al-Shareefi AN, Al-Nimer MS, Aljebory HD, Hasan BT. Assessment of insulin resistant and the related cardio-metabolic factors in overweight-obese women presented with missed abortion, Baghdad, Iraq. Saudi J Obesity [serial online] 2015 [cited 2023 Jun 2];3:66-71. Available from: https://www.saudijobesity.com/text.asp?2015/3/2/66/171961

Introduction

Maternal overweight and obesity may have implications for infant health and pregnancy outcome. ^[1] Regarding the maternal health, there is a causal relationship between maternal weight changes that occurred between consecutive pregnancies with the complications of pregnancy. ^[2] Obese women are more likely to have complications of pregnancy included preeclampsia, diabetic disorders, ^[3],[4] and increased risk of spontaneous preterm delivery (≤27 completed weeks). ^[5] Regarding the infant health, maternal obesity is a risk factor of infant deaths due to congenital anomalies and sudden infant death syndrome. ^[6],[7] A Recent study shows that there is a small positive association between obesity and the risk of spontaneous abortion. ^[8] This association becomes stronger for early spontaneous abortion; that is <8 weeks gestation. ^[8] Therefore, obesity is a potentially modifiable prepregnant risk factor that associated with increased miscarriage risk. ^[9] Moreover, obese women with recurrent early pregnancy loss have an increased frequency of chromosomal euploid miscarriage as a result of high rate of maternal cell contamination in the prior miscarriage. ^[10] Fasting serum insulin levels and insulin resistance (IR) (determined by homeostatic model assessment-IR; [HOMA-IR]) are higher in women with idiopathic recurrent pregnancy loss (<20 weeks gestation) than those women without spontaneous abortion. ^[11] Possibly, the explanation of the association between the miscarriage with the IR is attributed to multiple pathological entities that induced by hyperinsulinemia including hypercoagulability, increased production of cytokines and metabolic derangements. ^{[12],[13],[14]} In one study, women who have normal prepregnant glucose metabolism and presented with recurrent spontaneous abortion tended to be more insulin resistant during first-trimester pregnancy than healthy controls. ^[15] The relationship between obesity, miscarriage, and cardio-metabolic risk factors is not studied. There is no doubt that obesity is one important component of the cardio-metabolic risk factors, and it commonly associated with miscarriage as mentioned above. Xu et al., reported that spontaneous abortion is associated nonsignificantly with cardio-metabolic risk factors. ^[16] Therefore, in respect to the above-mentioned studies, IR may play a role in the pathogenesis of recurrent abortion, and it behaves as a key link between pregnancy loss and obesity. This study aimed to assess the status of IR, using HOMA-IR model, in overweight-obese women presented with missed abortion and to look for the presence of other cardio-metabolic risk factors.

Materials and methods

This study was conducted in the Department of Obstetrics and Gynecology at Al-Yarmouk Teaching Hospital in cooperation with Department of Pharmacology, College of Medicine, Al-Mustansiriya University, from March 1, 2014, to January 31, 2015. A consent form obtained from each patient prior to the admission into the study. This study was conducted according to the ethical guidelines constructed by the Scientific Committee of the Institute in which the treatment or the using device should be a part of disease management; should not be harmful to the patient, and the patient is free to decline from the study or to refuse for study admission.

The criteria of inclusion are missed abortion confirmed by ultrasonography who admitted in the obstetrics ward at Al-Yarmouk Teaching Hospital for management and follow-up.

Exclusion criteria included the history of diabetes mellitus, chronic liver diseases, renal disorders, autoimmune disease, and hypersensitivity to the medications including prostaglandins analogs, for example, misoprostol. A total number of 60 women fulfill the above criteria were enrolled in this study. On admission, the demographic characteristics, medical, and obstetric history from each patient were obtained. On the admission, the following measurements; anthropometric and the blood pressure were determined. The anthropometric measurements included weight (kg), height (m), and waist circumference (cm). The body mass index (BMI) is calculated using the Quetlet's equation:

The blood pressure (mmHg) was measured by auscultation method with the properly calibrate mercury sphygmomanometer on lying position, and the mean of three readings was taken. The difference between systolic and diastolic blood pressure represented the pulse pressure, and the mean arterial blood pressure is equal to diastolic blood pressure + (1/3 × pulse pressure). Fasting peripheral venous blood was drawn into tubes, and then the samples were centrifuged at 2500 rpm for 10 min, and the sera were separated for determination of fasting lipid profile total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-c), fasting serum glucose, and fasting insulin.

Serum very low-density lipoprotein-cholesterol concentration (mg/dl) is calculated by using the following formula: Serum TG × 0.2.

The LDL-cholesterol is determined by using the

Bio Vision's human insulin (Inc., USA) kit, an in vitro enzyme-linked immunosorbent assay for the quantitative measurement of human insulin, is used in this study to determine the fasting insulin levels. This assay employs an antibody specific for human insulin coated on a 96-well plate. Standards and samples are pipetted into the wells and insulin present in a sample is bound to the wells by the immobilized antibody. The wells are washed, and biotinylated anti-human insulin antibody is added. After washing away unbound biotinylated antibody, horseradish peroxidase-conjugated streptavidin is pipetted to the wells. The wells are again washed, a 3,3', 5, 5'-tetramethylbenzidine substrate solution is added to the wells and color develops in proportion to the amount of insulin bound. The stop solution changes the color from blue to yellow, and the intensity of the color is measured at 450 nm. The minimum detectable dose of insulin is typically <4 μU/ml. The HOMA-IR and insulin sensitivity (IS) (the reciprocal value of HOMA-IR) were calculated by using the following equations:

The lines of management that instructed by the consultants including a therapeutic regimen of misoprostol with/without dilatation and curettage (D and C) according to the patient response. Misoprostol is administered as a vaginal or oral tablet (200 μg strength) with a frequency that depended on the patient condition and decided by the opinion of the consultant. Each patient is assessed and followed up taking in consideration the outcome of misoprostol, i.e. the successful expulsion of the uterine content, surgical intervention in term of D and C, complications of missed abortion included bleeding, infections, the requirement of antibiotics and/or intravenous fluids and monitoring the adverse reactions of misoprostol.

According to the BMI value, the patients were grouped into two groups:

Group I (nonobese; n = 15): Women with a BMI <25 kg/m ²
Group II (overweight-obese; n = 45): Women with a BMI ≥25 kg/m ² .

Statistical analysis

The data are present as a number, percent, mean ± standard deviation (SD) or median. Unpaired Student's t-test was used to evaluate differences between the two groups and the simple correlation test was applied for the association between the independent and dependent factors. For all tests, a two-tailed P ≤ 0.05 is a cut-off level of statistically significant. All calculations were made using Excel 2003 program for Windows (Microsoft cooperation, Redmond, USA).

Results

[Table 1] shows the characteristics of patients enrolled in the study. There are nonsignificant differences between Group I and II in respect to the age, clinical presentations, family history of missed abortion, or the habit of smoking. The most common presenting clinical sign is a slight vaginal bleeding of variable duration. The previous history of hypertension and polycystic ovarian syndrome observed in 4.4 and 6.7%, respectively in Group II compared with 0% in Group I. Previous history of obesity is reported in 33.3% of Group II patients compared with 0% in Group I, a difference reached to a significant level (P = 0.000). At the time of the entry into the study, 6.7% of women in Group II received metformin therapy as a part of the management of the polycystic ovarian disease. There are significant differences between Group I and II regarding the gravidity and parity [Table 1]. At the time of presentation, the median gestation age was 12 and 11 for Group I and II, which did not significantly differ. Folic acid supplementation observed in 80% and 60% in Group I and II, respectively. The previous history of missed abortion was significantly observed in a higher percent (35.6%) in Group II compared with Group I (6.7%) [Table 1]. History of preeclampsia existed in 4.4% in overweight-obese women (Group II) compared to 0% in nonoverweight-obese women (Group I). Cardio-metabolic risk factors in term of obesity, high blood pressure, high atherogenic lipid levels, and low HDL-c were significantly observed in Group II compared with Group I [Table 2]. Fasting serum glucose was significantly higher (85.5 ± 14.7 mg/dl) in overweight-obese women compared with nonobese women (80.7 ± 3.5 mg/dl) presented with missed abortion [Table 3]. The mean fasting serum insulin levels is higher in overweight-obese women compared with nonobese women complained from missed abortion (13.0 ± 0.5 μU/ml vs. 12.2 ± 0.3 μU/ml, P < 0.02). The mean level of HOMA-IR that observed in overweight-obese women presented with missed abortion is above the cut-off of IR, i.e. 2.6 [Table 3]. The mean ± SD levels of HOMA-IR index are 2.43 ± 0.11 versus 2.75 ± 0.5 (P < 0.02) for Group I and II, respectively. The IS that represented the reciprocal IR value showed significantly high levels among nonobese women compared with overweight-obese women. Significant positive correlation between HOMA-IR with BMI observed in Group II but not in Group I [Figure 1].

Figure 1: Significant correlation between body mass index and homeostatic model assessment-insulin resistance in Group II (r = 0.364, P < 0.01) and insignificant correlation in Group I (r = 0.264, P > 0.05)

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Table 1: Participants of the study

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Table 2: Cardio-metabolic risk factors among participants

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Table 3: Assessment of glycemic HOMA-IR among participants

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There were nonsignificant differences between Group I and II regarding the route of misoprostol administration, total doses and the onset of response [Table 4]. Supplemented surgical intervention (D and C) is indicated in a significant high percent (75.6%) of patients in Group II compared with 13.3% of patients in Group I [Table 4]. Vaginal bleeding that related to the management of missed abortion reported significantly in Group II compared with Group I (24.4% vs. 6.7%, P = 0.02). Hypotension as an adverse reaction of misoprostol is observed in 2 out 45 (4.2%) women in Group II.

Table 4: Current management

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Discussion

The results of this study show that obese women presented with missed abortion have insulin resistant with significant high levels of cardio-metabolic risk factors compared with lean women, and this reflected on the outcome of their management. Obesity through different mechanisms may cause missed abortion. There is evidence that obese women are more likely to have a significant increase of euploid miscarriage suggested that the risk of missed abortion is independently associated with embryonic aneuploidy. ^[17] In this study, obstetric history revealed that previous history of obesity and missed abortion are significantly present in Group II which indicates that the association of missed abortion and obesity is a continuous process. Previous studies mentioned the maternal and perinatal complications that happened in obese women, but they did not mention the hazard of cardio-metabolic risk factors that associated with obese women presented with missed abortion. ^[18],[19] Shopen et al. demonstrated that pregnancy induced hypertension is more likely to persist in the future as chronic hypertension in obese women. ^[20] In this study, the blood pressure is within the normal limits but significantly higher in Group II compared with Group I which indicates that the high blood pressure is associated with missed abortion as a result of obesity. Kharazmi et al. reported that the risk of cardiovascular diseases such as hypertension, acute myocardial infarction are increased later in the life of a woman who had a history of repeated missed abortion. ^[21] The significant high insulin resistant index that found in Group II may play a role in the pathogenesis of missed abortion because about one-third of Group II women had a previous history of obesity, and the insulin resistant might be exist even before gestation. ^[22] Moreover, the insulin resistant that reported in Group II may be in the future will cause type 2 diabetes. ^[22] The results of this study are in agreement with Ispasoiu et al. study that reported that fasting insulin levels and HOMA-IR index are significantly higher in women with recurrent idiopathic pregnancy loss. ^[11] This study also shows a significant correlation between insulin resistant and obesity, that is, morbid obesity (high BMI) have a higher HOMA-IR index and a more hazard on the maternal and neonatal health. The management outcome is inferior in Group II compared with Group I in term of indications of surgical intervention and the occurrence the adverse effects of misoprostol. ^[23] Limitations of the study included small sample size, and the cytogenetic analysis did not carry on. We conclude that IR is associated with missed abortion and carried adverse events on the management outcome. Therefore, determination of HOMA-IR and assessment of cardio-metabolic risk factors should be considered in obese women presented with missed abortion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Guelinckx I, Devlieger R, Beckers K, Vansant G. Maternal obesity: Pregnancy complications, gestational weight gain and nutrition. Obes Rev 2008;9:140-50.
2.	Villamor E, Cnattingius S. Interpregnancy weight change and risk of adverse pregnancy outcomes: A population-based study. Lancet 2006;368:1164-70.
3.	Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785-99.
4.	Correa A, Gilboa SM, Besser LM, Botto LD, Moore CA, Hobbs CA, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol 2008;199:237.e1-9.
5.	Cnattingius S, Villamor E, Johansson S, Edstedt Bonamy AK, Persson M, Wikström AK, et al. Maternal obesity and risk of preterm delivery. JAMA 2013;309:2362-70.
6.	Stothard KJ, Tennant PW, Bell R, Rankin J. Maternal overweight and obesity and the risk of congenital anomalies: A systematic review and meta-analysis. JAMA 2009;301:636-50.
7.	Johansson S, Villamor E, Altman M, Bonamy AK, Granath F, Cnattingius S. Maternal overweight and obesity in early pregnancy and risk of infant mortality: A population based cohort study in Sweden. BMJ 2014;349:g6572.
8.	Hahn KA, Hatch EE, Rothman KJ, Mikkelsen EM, Brogly SB, Sørensen HT, et al. Body size and risk of spontaneous abortion among danish pregnancy planners. Paediatr Perinat Epidemiol 2014;28:412-23.
9.	Feodor Nilsson S, Andersen PK, Strandberg-Larsen K, Nybo Andersen AM. Risk factors for miscarriage from a prevention perspective: A nationwide follow-up study. BJOG 2014;121:1375-84.
10.	Boots CE, Bernardi LA, Stephenson MD. Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril 2014;102:455-9.
11.	Ispasoiu CA, Chicea R, Stamatian FV, Ispasoiu F. High fasting insulin levels and insulin resistance may be linked to idiopathic recurrent pregnancy loss: A case-control study. Int J Endocrinol 2013;2013:576926.
12.	Glueck CJ, Wang P, Fontaine RN, Sieve-Smith L, Tracy T, Moore SK. Plasminogen activator inhibitor activity: An independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism 1999;48:1589-95.
13.	Nagaev I, Bokarewa M, Tarkowski A, Smith U. Human resistin is a systemic immune-derived proinflammatory cytokine targeting both leukocytes and adipocytes. PLoS One 2006;1:e31.
14.	Quéré I, Mercier E, Bellet H, Janbon C, Marès P, Gris JC. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001;75:823-5.
15.	Hong Y, Xie QX, Chen CY, Yang C, Li YZ, Chen DM, et al. Insulin resistance in first-trimester pregnant women with pre-pregnant glucose tolerance and history of recurrent spontaneous abortion. J Biol Regul Homeost Agents 2013;27:225-31.
16.	Xu B, Zhang J, Xu Y, Lu J, Xu M, Chen Y, et al. Association between history of abortion and metabolic syndrome in middle-aged and elderly Chinese women. Front Med 2013;7:132-7.
17.	Landres IV, Milki AA, Lathi RB. Karyotype of miscarriages in relation to maternal weight. Hum Reprod 2010;25:1123-6.
18.	Crane JM, Murphy P, Burrage L, Hutchens D. Maternal and perinatal outcomes of extreme obesity in pregnancy. J Obstet Gynaecol Can 2013;35:606-11.
19.	Marchi J, Berg M, Dencker A, Olander EK, Begley C. Risks associated with obesity in pregnancy, for the mother and baby: A systematic review of reviews. Obes Rev 2015;16:621-38.
20.	Shopen N, Schiff E, Koren-Morag N, Grossman E. Factors that predict the development of hypertension in women with pregnancy-induced hypertension. Am J Hypertens 2015. pii: Hpv073.
21.	Kharazmi E, Fallah M, Luoto R. Miscarriage and risk of cardiovascular disease. Acta Obstet Gynecol Scand 2010;89:284-8.
22.	Gutaj P, Sawicka-Gutaj N, Brazert M, Wender-Ozegowska E. Insulin resistance in pregnancy complicated by type 1 diabetes mellitus. Do we know enough? Ginekol Pol 2015;86:219-23.
23.	Strafford MA, Mottl-Santiago J, Savla A, Soodoo N, Borgatta L. Relationship of obesity to outcome of medical abortion. Am J Obstet Gynecol 2009;200:e34-6.