Comparison of Hematologic and Biochemical Factors between Women with Gestational Diabetes and Healthy Pregnant Women


Alireza Ahmadi
(PhD) Laboratory Science Research Center, Faculty of Paramedicine of Golestan University of Medical Sciences, Gorgan, Iran
Mahdi Ghasemian
(MSc) Laboratory Science Research Center, Faculty of Paramedicine of Golestan University of Medical Sciences, Gorgan, Iran
Aliasghar Ayatollahi
(PhD) Laboratory Science Research Center, Faculty of Paramedicine of Golestan University of Medical Sciences, Gorgan, Iran
Murtdha Al-Khabori
(MD) Hematology Department, COM&HS, Sultan Qaboos University, Muscat, Oman 
Mohammad Taher Hojjati
(PhD) Laboratory Science Research Center, Faculty of Paramedicine of Golestan University of Medical Sciences, Gorgan, Iran
 
Corresponding author: Mohammad Taher Hojjati
Email: dr.hojati@goums.ac.ir
Tel: +989113562819
Address: Laboratory Science research center, faculty of Paramedicine of Golestan University of medical sciences

 

ABSTRACT

Background and objectives: Diagnosis glucose intolerance in pregnancy is very important in preventing maternal and fetal complications. In this study, we compared hematological and biochemical characteristics of healthy pregnant women and women with gestational diabetes mellitus (GDM) to find predisposing and prognostic variables of GDM.

Methods: In this study, 80 pregnant women (at 24-28 weeks of pregnancy) were divided into a GDM group and non-GDM group by performing oral glucose tolerance test using 75 g glucose according to the International Association of the Diabetes and Pregnancy Study Groups criteria.
Results: The mean age of women with GDM was significantly higher than those without GDM (p=0.048). Other variables including body mass index, gestational age and daily sleep duration did not differ significantly between the two groups (P>0.05). There was a significant association between family history of diabetes and incidence of GDM (p=0.040). In addition, the C-peptide level was significantly higher in pregnant women with GDM (p=0.004).
Conclusion: Considering the role of C-peptide in predicting metabolic syndrome, it is suggested to use this factor for identification of GDM patients.
Keywords: Gestational diabetes, C-peptide, CRP, GTT
 
INTRODUCTION
Diabetes diagnosed for the first time during pregnancy is called gestational diabetes mellitus (GDM) (1), which has adverse effects on the mother and fetus (2). The prevalence of type 2 diabetes in women with a history of GDM is reported to be 3-65%. Children also suffer from complications of GDM such as obesity and diabetes in the future (3). Important maternal complications of GDM include preeclampsia, eclampsia, birth canal injuries, polyhydramnios and a higher risk of maternal bacterial infections. Increased size of the fetus can result in maternal injury and increase the risk of perinatal mortality (4). Glycemic control, screening mothers and timely diagnosis and treatment of GDM can significantly reduce the risk of these complications (5-7). In this study, we compare hematological and biochemical characteristics of healthy pregnant women and those with GDM to find predisposing and prognostic variables of GDM.
 
MATERIALS AND METHODS
The study was performed on 80 pregnant women with gestational age of 24 to 28 weeks who had been referred to the laboratories of Gorgan (Iran) for diabetes screening. The subjects were divided into two groups of GDM (n=40) and non-GDM (n=40) by performing oral glucose tolerance test using 75 g glucose according to the International Association of the Diabetes and Pregnancy Study Groups criteria.
Demographic data were collected using a 12-item questionnaire. The study was approved by the ethics committee of the Golestan University of Medical Sciences (ethics code: IR.GOUMS.REC.1400.043). Written informed consent was taken from the subjects prior to participation. Five ml of fasting blood were taken for biochemical tests. All patients were explained how to consume 75 g of glucose. Samples were also taken one hour and two hours after the first sampling for glucose tolerance test (GTT). Complete blood count (CBC) and erythrocyte sedimentation rate (ESR) tests were performed using ABACUSE-5 cell counter (Diatron, France) and Sedimex analyzer (Sedimex, USA), respectively. Fasting blood sugar (FBS), 1-hour GTT, 2-hour GTT, amylase, zinc and C-reactive protein (CRP) were analyzed using the HITACHI-911 autoanalyzer (HITACHI, Japan).
Blood sugar was measured by Pars Azmoun kit (Iran) using the glucose oxidase method. C-peptide level was measured by ELISA using Monobind kit (USA) according to the kit manufacturer's protocol. The measurements were carried out using an ELISA reader (SYGMA Diagnostic, SYGMA, Australia).
Based on the results glucose test, the subjects were divided into two groups of GDM and non-GDM. According to the International Association of the Diabetes and Pregnancy Study Groups criteria (8), presence of one or more of the following confirmed GDM: FBS ≥ 92 mg/dl, 1-hour GTT≥ 180 mg/dl, 2-hour GTT≥ 153 mg/dl.
Results were presented as mean ± standard deviation. Data were analyzed using SPSS 16. The t-test was used for analyzing normal distributed independent samples and the Mann Whitney U test was used for analyzing non-normally distributed data. The Chi-square test was used for comparing categorical data. Significance level was set at 0.05 for all tests.
 
RESULTS
The mean age of pregnant women was 29.17 ± 5.6 years (range: 18-40 years). The mean gestational age was 25 ± 1.7 weeks (range: 24-28 weeks). The mean body mass index (BMI) and sleep duration were 27.4 ± 4.4 kg/m² (range: 17.7-40 kg/m²) and 9.25 hours per day (range: 5-15 hours per day), respectively.
Of 80 participants, five (6.25%) had a history of diabetes, 35 (43.8%) had a family history of diabetes and 30 (37.5%) had consanguineous marriages.
As shown in table 1, the mean age of patients with GDM was significantly higher than that of those without GDM (p=0.048). However, there was no significant difference between pregnant women with and without GDM in terms of BMI, gestational age and daily sleep duration. The results also showed no significant difference between the groups in terms of history of diabetes (P>0.05).
 
Table 1. Demographic information of pregnant women with and without GDM

 
There was no significant relationship between history of consanguineous marriage and the incidence of GDM (p=0.617). The C-peptide level was significantly higher in the GDM group compared with the non-GDM group (p=0.004). However, there was no significant difference between the two groups in terms of other variables (Table 2).
 
Table 2. Comparison of laboratory findings between pregnant women with and without GDM

BS.1hPP: 1 hour post prandial
BS.2hPP: 2 hour post prandial
 
 
DISCUSSION
The present study compared demographic, hematological and biochemical characteristics of pregnant women with and without GDM. The mean age of women with GDM group was significantly higher than that in the non-GDM group, indicating that the risk of GDM increases with the age. Based on previous studies, age, obesity and family history of diabetes are important risk factors of GDM (9-16). In our study, there was a significant relationship between GDM and family history of diabetes. However, no such relationship was observed in studies in Nigeria (17), Sri Lanka (18) and Iran (19).
Growing evidence suggests that poor sleep may contribute to the development of GDM (20-22). Many studies have examined the effect of sleep duration on incidence of GDM. Jahanpak et al. reported that the daily sleep duration changes in pregnancy are associated with impaired glucose metabolism (23). In another study, Cai et al. reported that poor sleep quality or short nocturnal sleep during pregnancy contributed to abnormal glucose regulation, and treating sleep problems could potentially reduce the risk and burden of GDM (24). One of the primary outcomes of poor sleep quality is glucose intolerance, which is defined as the inability to maintain euglycemia by metabolizing exogenous glucose via insulin-dependent and non-insulin-dependent mechanisms (25). However, in our study, we observed no significant relationship between sleep duration and GDM.
The C-peptide is a useful marker of beta-cell function and endogenous insulin secretion since it is produced in equal amounts to insulin (26). A study by Yin et al. found a positive association between serum C-peptide levels and the risk of diabetes and pre-diabetes among Chinese women with a history of GDM (27). In a study by Homko et al., women with GDM had a major β-cell defect and increased level of insulin resistance, which occurred during late pregnancy (28). Similarly, Fatima et al. introduced C-peptide as a predictive factor for GDM (29).
We found no significant difference between the two groups in terms of plasma zinc level. Inconsistent with this finding, previous studies reported that pregnant women with GDM have significantly lower plasma zinc level compared to non-GDM counterparts (30-32).
As an inflammatory marker, serum CRP level can be associated with an increased risk of diabetes (33). In our study, serum CRP level did not differ significantly between the two groups, which is in line with findings of D'Anna et al. (34). However, other studies have reported CRP as an important predictor of GDM (35, 36).
Amylase is an enzyme secreted by the pancreas that increases in pancreatitis (37). The amylase level did not differ significantly between pregnant women with and without GDM, which is consistent with findings of a study by Khosrowbeygi et al. (38). However, a previous study reported that patients with GDM had significantly lower levels of serum amylase than those without GDM (39). In another study, Yu et al. reported that pregnant women with GDM had higher plasma amylase level compared to healthy pregnant women (40).
Results of studies on the relationship of hematological indicators and complications of pregnancy have been contradictory (41). In this regard, a study by Zafari et al. reported no significant difference in hemoglobin levels between the GDM and non-GDM groups (42), which were consistent with our results. In a study by Lao et al. (43), hemoglobin level of more than 13 g/dl was found as effective factor in the development of GDM, which can be due to increased iron intake. In line with this finding, Helin et al. claimed that unnecessary iron intake in the first trimester of pregnancy is associated with an increased risk of GDM (44).
 
CONCLUSION
Given the importance of GDM and its complications, it is essential to find predictive markers for early diagnosis of the condition. Based on the results, it is suggested to use C-peptide as an important factor for identifying GDM during pregnancy.
 
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
 
References
1. Jang HC, Cho NH, Jung KB, Oh KS, Dooley SL, Metzger BE. Screening for gestational diabetes mellitus in Korea. Int J Gynaecol Obstet. 1995; 51: 115-22. [View at Publisher] [DOI] [PubMed] [Google Scholar]
2. Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care. 1998; 21 (Suppl 2): B161-7. [View at Publisher] [DOI] [Google Scholar]
3. Niyafar M, Salem A, Ali Asgharzadeh A. Risk factors for gestational diabetes and prevalence of impaired glucose tolerance six weeks after delivery. Med J Tabriz Uni Med Sciences Health Services. 2017; 39: 73-80. [Persian] [View at Publisher] [Google Scholar]
4. Hare JW. Diabetic complications of diabetic pregnancies. Semin Perinatol. 1994;18: 451-8. [PubMed] [Google Scholar]
5. Schmidt MI, Duncan BB, Reichelt AJ, Branchtein L, Matos MC, Costa e Forti A, et al. Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes. Diabetes Care. 2001; 24(7): 1151-5. [View at Publisher] [DOI:10.2337/diacare.24.7.1151] [PubMed] [Google Scholar]
6. Pettitt DJ, Nelson RG, Saad MF, Bennett PH, Knowler WC. Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care 1993;16: 310-4. [View at Publisher] [DOI:10.2337/diacare.16.1.310] [PubMed] [Google Scholar]
7. Sacks DA, Greenspoon JS, Abu-Fadil S, Henry HM, Wolde-Tsadik G, Yao JF. Toward universal criteria for gestational diabetes: the 75-gram glucose tolerance test in pregnancy. Am J Obstet Gynecol 1995; 172: 607-14. [View at Publisher] [DOI:10.1016/0002-9378(95)90580-4] [PubMed] [Google Scholar]
8. Kyu Yeon Hur. New Diagnostic Criteria for Gestational Diabetes Mellitus and Pregnancy Outcomes in Korea. Diabetes Metab J. 2019; 43(6): 763-765. [DOI:10.4093/dmj.2019.0247] [PubMed] [Google Scholar]
9. Goli M, Firouzeh F. Prevalence of gestational diabetes and efficacy of risk factors in screening of referrals to health centers. J Holist Nurs Midwifery 2014; 24 :56-63.[Persian] [View at Publisher] [Google Scholar]
10. Yang X, Hsu-Hage B, Zhang H, Yu L, Dong L, Li J, Shao P, et al. Gestational diabetes mellitus in women of single gravidity in Tianjin City, China. Diabetes Care. 2002; 25: 847-51. [View at Publisher] [DOI:10.2337/diacare.25.5.847] [PubMed] [Google Scholar]
11. Kafkasli AC, Sertkaya AB, Selcuk E, Dogan K, Burak F, Yologlu S. Abnormal Glucose Challenge Test and Mild Gestational Diabetes. Gynaecologia et perinatologia. 2008; 17: 3-8. [View at Publisher] [Google Scholar]
12. Monteiro G, Subbalakshmi NK, Pai SR. A study on clinical characteristics of gestational diabetes mellitus associated with intrauterine fetal death. IJBR 2014; 5(1): [View at Publisher] [Google Scholar]
13. Vakili M, Rahimi Pardanjani S, Alipour N, Taheri M, Baeradeh N, Hashemi A. The prevalence of gestational diabetes and associated factors in pregnant women referred to health care centers of Yazd in 2012. J Sabzevar Univ Med Sci. 2015; 21(6): 1214-24. [Persian] [View at Publisher] [Google Scholar]
14. McCarthy AD, Curciarello R, Castiglione N, Tayeldín MF, Costa D, Arnol V, et al. Universal versus selective screening for the detection, control and prognosis of gestational diabetes mellitus in Argentina. Acta Diabetol. 2010; 47(2): 97-103. [View at Publisher] [DOI] [PubMed] [Google Scholar]
15. Maegawa Y, Sugiyama T, Kusaka H, Mitao M, Toyoda N. Screening tests for gestational diabetes in Japan in the 1st and 2nd trimester of pregnancy. Diabetes Res Clin Pract 2003;62:47-53. [View at Publisher] [DOI:10.1016/S0168-8227(03)00146-3] [PubMed] [Google Scholar]
16. Khatun N, Latif SA, Uddin MM. Risk factors for the development of gestationaldiabetes mellitus. Mymensingh Med J 2009;18(1 Suppl):S20-23. [PubMed] [Google Scholar]
17. Rodrigues S, Robinson E, Gray-Donald K. Prevalence of gestational diabetes mellitus among James Bay Cree women in northern Quebec. CMAJ. 1999; 4; 160: 1293-7. [View at Publisher] [PubMed] [Google Scholar]
18. Siribaddana SH, Deshabandu R, Rajapakse D, Silva K, Fernando DJ. The prevalence of gestational diabetes in a Sri Lankan antenatal clinic. Ceylon Med J. 1998;43(2):88-91. PubMed PMID: 9704548. [PubMed] [Google Scholar]
19. Kashi Z, Borzouei Sh, Akha O, Moslemizadeh N, Zakeri H, Mohammad Poor A, et al. Diagnostic Value of Fasting Plasma Glucose in Screening of Gestational Diabetes Mellitus. Int Endocrinol Metab. 2007; 5: 1-4. [persian] [View at Publisher] [Google Scholar]
20. Reutrakul S., Van Cauter E. Interactions between sleep, circadian function, and glucose metabolism: implications for risk and severity of diabetes. Ann. N. Y. Acad. Sci. 2014; 1311: 151-173. [View at Publisher] [DOI:10.1111/nyas.12355] [PubMed] [Google Scholar]
21. Myoga M, Tsuji M, Tanaka R, Shibata E, Askew DJ, Aiko Y, et al. Impact of sleep duration during pregnancy on the risk of gestational diabetes in the Japan environmental and Children's study (JECS). BMC Pregnancy Childbirth. 2019; 19(1): 483. [View at Publisher] [DOI:10.1186/s12884-019-2632-.] [PubMed] [Google Scholar]
22. Gooley JJ, Mohapatra L, Twan DCK. The role of sleep duration and sleep disordered breathing in gestational diabetes mellitus. Neurobiol Sleep Circadian Rhythms. 2017; 4: 34-43. [View at Publisher] [DOI:10.1016/j.nbscr.2017.11.001] [PubMed] [Google Scholar]
23. Jahanpak N, Razmjoo N, Rezaei Ardani A, Mazloum S, Bonakdaran S. The Relationship between Sleep Duration and Glucose Challenge Test Results in Pregnant Women without Risk Factors of Diabetes. The Iranian Journal of Obstetrics, Gynecology and Infertility, 2013; 16(60): 9-17. [View at Publisher] [DOI] [Google Scholar]
24. Cai S, Tan S, Gluckman PD, Godfrey KM, Saw SM, Teoh OH, et al. GUSTO study group. Sleep Quality and Nocturnal Sleep Duration in Pregnancy and Risk of Gestational Diabetes Mellitus. Sleep. 2017; 40(2). [View at Publisher] [DOI:10.1093/sleep/zsw058] [PubMed] [Google Scholar]
25. O'Keeffe M, St-Onge MP. Sleep duration and disorders in pregnancy: implications for glucose metabolism and pregnancy outcomes. Int J Obes (Lond). 2013;37(6):765-770. doi:10.1038/ijo.2012.142. [View at Publisher] [DOI:10.1038/ijo.2012.142] [PubMed] [Google Scholar]
26. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013; 30(7):803-17. [View at Publisher] [DOI:10.1111/dme.12159] [PubMed] [Google Scholar]
27. Yin P, Shao P, Liu H, et al. C-peptide levels and the risk of diabetes and pre-diabetes among Chinese women with gestational diabetes. J Diabetes Complications. 2017; 31(12):1658-1662. [View at Publisher] [DOI:10.1016/j.jdiacomp.2017.08.006] [PubMed] [Google Scholar]
28. Homko C, Sivan E, Chen X, Reece EA, Boden G. Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab. 2001; 86(2): 568-73. [View at Publisher] [DOI:10.1210/jcem.86.2.7137] [PubMed] [Google Scholar]
29. Fatema N, Deeba F, Akter S, Sultana N, Nasrin B, Ali L, et al. CRP(C-reactive protein) in Early Pregnancy Predictor for Development of GDM. Mymensingh Med J. 2016; 25: 271-6. [PubMed] [Google Scholar]
30. Wang Y, Tan M, Huang Z, Sheng L, Ge Y, Zhang H, et al. Elemental contents in serum of pregnant women with gestational diabetes mellitus. Biol Trace Elem Res 2002;88:113-8. [View at Publisher] [DOI:10.1385/BTER:88:2:113] [PubMed] [Google Scholar]
31. Bo S, Lezo A, Menato G, Gallo ML, Bardelli C, Signorile A, et al. Gestational hyperglycemia, zinc, selenium, and antioxidant vitamins. Nutrition. 2005; 21(2): 186-91. [View at Publisher] [DOI:10.1016/j.nut.2004.05.022] [Google Scholar]
32. Ugwuja E, Akubugwo EI, Ejikeme B. Plasma Copper and Zinc in Pregnancy Complicated with Diabetes Mellitus. Pakistan Journal of Nutrition. 2010; 9: 861-864. [DOI:10.3923/pjn.2010.861.864] [Google Scholar]
33. Qiu C, Sorensen TK, Luthy DA, Williams MA. A prospective study of maternal serum C-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatr Perinat Epidemiol. 2004 Sep;18(5):377-84. [View at Publisher] [DOI:10.1111/j.1365-3016.2004.00578.x] [PubMed] [Google Scholar]
34. D'Anna R, Baviera G, De Vivo A, Facciolà G, Di Benedetto A, Corrado F.C-reactive protein as an early predictor of gestational diabetes mellitus. J Reprod Med. 2006; 51(1): 55-8. [PubMed] [Google Scholar]
35. Wolf M, Sandler L, Hsu K, Vossen-Smirnakis K, Ecker JL, Thadhani R.First-trimester C-reactive protein and subsequent gestational diabetes. Diabetes Care 2003 Mar;26:819-24. [View at Publisher] [DOI:10.2337/diacare.26.3.819] [PubMed] [Google Scholar]
36. Leipold H, Worda C, Gruber CJ, Prikoszovich T, Wagner O, Kautzky-Willer A.Gestational diabetes mellitus is associated with increased C-reactive protein concentrations in the third but not second trimester. Eur J Clin Invest 2005;35:752-7. [View at Publisher] [DOI:10.1111/j.1365-2362.2005.01574.x] [PubMed] [Google Scholar]
37. Ahari U. Z, Falsafi P, Pouralibaba F, Eslami H, Maleki S, Pakdel F, Rahbar M. Comparison of Salivary Alpha Amylase and Peroxidase Levels in Women with GDM and Non-Diabetic Pregnant Women. Biomed Pharmacol J. 2016; 9(2). [View at Publisher] [DOI:10.13005/bpj/964] [Google Scholar]
38. Khosrowbeygi A, Shiamizadeh N, Taghizadeh N. Maternal circulating levels of some metabolic syndrome biomarkers in gestational diabetes mellitus. Endocrine. 2016 Feb;51(2):245-55. [DOI:10.1007/s12020-015-0697-4] [PubMed] [Google Scholar]
39. Ruoheng Zheng, Juanwen Zhang, Zhao Ying, Nengneng Zheng. Low Serum Amylase is Associated with Gestational Diabetes Mellitus in Chinese Pregnant Women. . 2015;61(10):1423-8. [DOI:10.7754/Clin.Lab.2015.150129] [PubMed] [Google Scholar]
40. Yu F, Zhou W, Tan X, Jiang Y. Gestational Diabetes Mellitus is Associated with Plasma Amylase in a Chinese Pregnant Women Population. Clin Lab. 2019 Jan 1;65(1). [View at Publisher] [DOI:10.7754/Clin.Lab.2018.180550] [PubMed] [Google Scholar]
41. Stephansson O, Dickman PW, Johansson A, Cnattingius S. Maternal hemoglobin concentration during pregnancy and risk of stillbirth. JAMA. 2000; 284(20): 2611-7. [View at Publisher] [DOI] [PubMed] [Google Scholar]
42. Zafari M, Aghamohammady A, Tofighi M, Tahmasebi H. The Relationship between Maternal HemoglobinConcen Tretion and Gestational Diabetes Melitus. International Journal of Nursing Science. 2011; 1: 9-11. [View at Publisher] [DOI:10.5923/j.nursing.20110101.02]
43. Lao TT, Chan LY, Tam KF, Ho LF. Maternal hemoglobin and risk of gestational diabetes mellitus in Chinese women. Obstet Gynecol. 2002; 99: 807-12. [View at Publisher] [DOI:10.1016/S0029-7844(02)01941-5] [PubMed] [Google Scholar]
44. Helin A, Kinnunen TI, Raitanen J, Ahonen S, Virtanen SM, Luoto R. Iron intake,haemoglobin and risk of gestational diabetes: a prospective cohort study. BMJ Open. 2012; 2. pii: e001730. [DOI:10.1136/bmjopen-2012-001730] [PubMed] [Google Scholar]