Skip to main content

Serum magnesium and high-sensitivity C-reactive protein as a predictor for gestational diabetes mellitus in Sudanese pregnant women



Gestational diabetes mellitus (GDM) is a big health problem that adversely affects both the maternal and perinatal outcomes. We aimed to predict the development of GDM in the first trimester using high sensitivity C-reactive protein (hs-CRP) and serum magnesium.


The study conducted in the antenatal care clinic of Saad Abualila Hospital (Khartoum, Sudan). Pregnant women were enrolled in this longitudinal cohort study during first trimester ≤14 weeks of gestation. Serum hs-CRP and magnesium concentrations were measured between weeks 11 and 14 of gestation. Glucose tolerance test and fasting plasma insulin (FPI) measurement were performed between 24 and 28 weeks gestational age. To assess insulin sensitivity and β-cell function, Homeostatic Model Assessment Insulin Resistance (HOMA-IR), HOMA-β indices and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated and used.


Out of the 126 who completed the study 19 (15%) were diagnosed as GDM. The median (interquartile) of FBG was significantly higher in women with GDM [81 (70–95) vs. 67(60–75) mg/dl; P = < 0.001] compared to women without GDM. There was no significant difference in hs-CRP, serum magnesium, HOMA-IR, QUICKI and HOMA- β between women with GDM and women without GDM. No correlation was observed between body mass index (BMI), serum magnesium, hs-CRP, FBG and insulin levels.


First trimester hs-CRP and serum magnesium levels were not correlated with the later development of gestational diabetes in this setting.

Peer Review reports


Gestational diabetes mellitus (GDM), according to American Diabetes Association (ADA) it is defined as a true diabetes that firstly recognized at first or second trimester and not proceeded by either type 1 or type 2 diabetes [1]. GDM among the major medical complication of pregnancy that can result in adverse health consequences for both the mother and the outcome [2]. Women with GDM are vulnerable to develop metabolic syndrome/type 2 diabetes later in life [3, 4]. Likewise, children born to mothers with GDM are threaten by glucose intolerance and obesity [5].

Screening to identify women at risk for GDM among pregnancies may allow more time for interventions and can yield a reduction in both GDM and its related adverse effects. Unfortunately, screening for GDM is commonly practiced after the 24th gestational week where there is a possible delay in implementing the desired/ planned interventions e.g. pharmacological therapy, diet, and exercise [6]. Therefore, there is a need for screening methods for GDM in detecting the risk of GDM in the first trimester of the pregnancy. Metabolic studies have detected various biomarkers that may be useful in early screening for GDM [7]. Low serum magnesium accompanied with high hs-CRP has been reported as a predictor for GDM in obese pregnant women [8]. It is known that magnesium promotes blood glucose reduction as it enhances the activity of the glucose transporter- 4 [9]. Moreover, it is directly involved in signalling transduction of the insulin receptor [10]. On the other hand, high serum hs-CRP increased in response to inflammatory reactions owing to insulin resistance observed in GDM [11]. Recent findings suggest serum magnesium and C-reactive protein could be used as predictors for GDM [8, 1219]. However, the results of these studies were variable and there is a need for further research in the different settings. Thus, the current study was conducted to investigate the correlation between serum magnesium, high sensitivity CRP (hs-CRP), glycaemic and insulin sensitivity index and to assess the performance of magnesium and hs-CRP in predicting GDM in the first trimester.

Materials and methods

A longitudinal cohort study was conducted at the antenatal care clinic of Saad Abualila Hospital (Khartoum, Sudan) during the period of January–November 2015. All women with singleton pregnancy, started antenatal care follow-up in the first trimester (≤14 weeks of gestation) were approached to participate in the study. Women with chronic disease e.g. thyroid disease, hypertension, renal disease, diabetes, liver disease and on medication were excluded from the study. After signing an informed consent, socio-demographic and obstetric characteristics were gathered by questionnaire (age, parity, gestational age, education, occupation and history of miscarriage). The weight and height were measured and body mass index (BMI) was computed (kg/m2). Pregnancy and its duration was confirmed by ultrasound operated in the clinic by a senior obstetrician. Then 5 ml of blood were withdrawn in EDTA tube, 2 mLs of it was used for hemogram and the rest were centrifuged and stored at − 20 °C until the assay of hs-CRP level, which was performed by EUROIMMUN analyser I-2P (Luebeck, Germany). The same procedure was used to measure insulin level lately in the third trimester. Atomic absorption spectrophotometry (SOLAAR, Atomic Absorption Spectrophotometer, Thermo Electron, Cambridge, UK) was used to determine levels of serum magnesium.

Then the enrolled women were followed in the antennal care clinic every month. According to the hospital policy, the glucose tolerance test was performed at 24–28 weeks of gestation. Recommended blood glucose levels determined by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and ADA were used to detect GDM among cases in this study. Which is described very briefly as one or more of the following blood glucose values met or exceeded; fasting blood glucose (FBG) ≥92 mg/dl, 1-h blood glucose was ≥180 mg/dl, and 2-h blood glucose ≥153 mg/dl, after 75-g oral glucose load [1, 19]. The study is adhered to STROBE guidelines [20].

Glucose oxidase test was used to assess the level of blood glucose (Shino-Test Corp. Tokyo, Japan). Insulin resistance was measured using the homeostasis model assessment (HOMA) of insulin resistance index (HOMA-IR) = fasting glucose level (mg/dl) × fasting insulin level (μU/ml) / 405 [21] and the quantitative insulin sensitivity check index (QUICKI) = 1 / [log fasting insulin level (μU/ml) + log fasting glucose level (mg/dl)] [22]. Insulin secretion was indicated by the HOMA of β-cell function (HOMA-β) (%) = 360 × fasting insulin level (μU/ml) / [fasting glucose level (mg/dl) − 63, [22].

Sample size calculated based on previous data [23], it was assumed that 13.9% of the pregnant women would experience gestational diabetes [23]. Allowing for 10% of participants to be lost to follow-up, a necessary sample size of 166 participants.


Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) for Windows, version 20.0 (SPSS Inc., Chicago, IL, USA). Proportions of the studied variables were expressed in numbers (%). Continuous data were checked for normality using Shapiro-Wilk test. The means (standard deviations) or median (interquartile) were used to describe the studied variables if normally and abnormally distributed, respectively. Spearman correlation was conducted between BMI, magnesium, hs-CRP, FBG and insulin sensitivity indices. Student’s t-test and Mann-Whitney U test _ if the data were not normally distributed_ were used to evaluate the mean differences between the studied groups. P <  0.05 was considered statistically significant.


One hundred and sixty women were initially enrolled, 126 (78.7%) women completed the follow-up, have complete data and analysed here. The main reason for the loss of follow-up was change of the address. The mean (SD) of gestational age in early pregnancy 10.2(2.4) and it was 26.5 (1.2) weeks at the time of the glucose tolerance testing.

General characteristics of the 126 enrolled women are shown in Table 1. Fifty-nine (46.8%) of the women were primiparae and 19 (15%) women had GDM.

Table 1 General characteristics of pregnant Sudanese women enrolled in early pregnancy

There was no correlation between, BMI, serum magnesium, hs-CRP, FBG and insulin level in the enrolled pregnant women (n = 126), Table 2.

Table 2 Spearman correlations between magnesium, hs-CRP, BMI, fasting blood glucose and insulin in the pregnant women (n = 126)

While FBG was significantly higher in women with GDM, BMI, serum magnesium, insulin, HOMA-IR, QUICKI and HOMA-β were not different in women with GDM (n = 19) and women who had no GDM (n = 107), Table 3.

Table 3 Comparing median(interquartile) level of body mass index, hs–CRP, magnesium, glycaemic and insulin sensitivity indices between women with GDM and controls


The current study shows no significant difference between serum magnesium, FBG and insulin resistance indices among women with GDM and women without GDM. Similarly, Nabouli et al. reported no significant difference in the serum magnesium level between women with GDM and women without GDM [16]. However, a significantly lower serum magnesium level, its association with insulin sensitivity and with fasting insulin in mothers with GDM have been reported before [8, 17, 18, 24]. Moreover, magnesium supplementations for magnesium deficient GDM patients’ result in a decrease of FBG, insulin, HOMA-IR, HOMA-B, hs-CRP and an increase of QUICKI [24]. Perhaps, hypomagnesemia lead to inadequate beta-cell compensation for the decrease in insulin sensitivity [25]. Interestingly, postpartum serum magnesium level was found to be a possible predictor for type 2 diabetes mellitus development in women with GDM [26]. We have previously observed a significantly lower median level of serum magnesium in diabetic patients with diabetic retinopathy compared with diabetic without diabetic retinopathy [27].

The hs-CRP level in the current study was not statistically different between women with GDM and women without GDM. This goes with Syngelaki et al. findings [14]. In contrast Fatema et al. and Ozgu-Erdinc et al. have recently reported a good performance (sensitivity and specificity) of hs-CRP in predicting GDM [12, 13]. Moreover, hs-CRP has been reported to be associated with insulin resistance, insulin index and GDM [15]. However, many reports claimed that CRP is positively correlated with pre-pregnancy BMI [28, 29]. Perhaps, our finding is partially attributed to the no difference observed in BMI and hs-CRP (which were expected to be higher in women with GDM). Yet Rota et al. [30] reported that the serum hs-CRP levels were significantly higher in GDM women despite no difference in the pre pregnancy BMI. In the later study glucose intolerance and weight gain during pregnancy were the main factors which affect hs-CRP levels. In our study BMI, hs-CRP were taken in early pregnancy without follow-up values. This point (measurement in early pregnancy) could be another explanation of the non-significant difference in hs-CRP in our study. Inflammatory mediators secreted from adipose tissue and placenta can lead to escalating low-grade inflammation during pregnancy specially in the third trimester [31, 32]. It worth mentioning that, almost 75% of our patients have BMI < 30 and this finding is not astonishing as the prevelance of pregnant women who have BMI < 30 in Sudan is 79% [33]. Alternatively, perhaps in GDM the insulin resistance is an effect of impairment of insulin action, rather than insulin secretion (similar to type 2 DM patients) with declining of insulin receptors and impairing intracellular glucose transport [34].


In summary, we fail to show any prediction of first trimester hs-CRP and serum magnesium with the development of GDM in this setting. Also, no correlation has been observed between insulin hormone level and insulin resistance indices, magnesium levels and hs-CRP.

This study has many limitations, firstly; the current study recruited small sample size and under power. The number of women with GDM is very low and comparison of them with women without GDM might not be reasonable. Secondly; other inflammatory markers e.g. cytokines were not measured and infections that might have effects on hs-CRP were not ruled out. Therefore, larger sample size with longitudinal study design is needed.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.



American Diabetes Association


Body Mass Index


Fasting Blood Glucose


Fasting Plasma Insulin


Gestational Diabetes Mellitus


Homeostatic Model Assessment Insulin Resistance


High Sensitivity C-Reactive Protein


International Association of Diabetes And Pregnancy Study Groups


Quantitative Insulin Sensitivity Check Index


Statistical Package for the Social Sciences


  1. 1.

    American Diabetes Association AD. 2. Classification and diagnosis of diabetes: standards of medical Care in Diabetes-2018. Diabetes Care. 2018;41(Supplement 1):S13–27.

  2. 2.

    Dall T, Yang W, Halder P, Pang B, Massoudi M. The economic burden of elevated blood glucose levels in 2012: diagnosed and undiagnosed diabetes, gestational diabetes mellitus, and prediabetes. Diabetes. 2014;37(12):3172–9.

    Article  Google Scholar 

  3. 3.

    Xu Y, Shen S, Sun L, Yang H, Jin B, Cao X. Metabolic Syndrome Risk after Gestational Diabetes: A Systematic Review and Meta-Analysis. Pasquali R, editor. PLoS One. 2014;9(1):e87863.

  4. 4.

    Rayanagoudar G, Hashi AA, Zamora J, Khan KS, Hitman GA, Thangaratinam S. Quantification of the type 2 diabetes risk in women with gestational diabetes: a systematic review and meta-analysis of 95,750 women. Diabetologia. 2016;59:1403–11.

    CAS  Article  Google Scholar 

  5. 5.

    Kim SY, England JL, Sharma JA, Njoroge T. Gestational diabetes mellitus and risk of childhood overweight and obesity in offspring: a systematic review. Exp Diabetes Res. 2011;2011:1–9.

    Article  Google Scholar 

  6. 6.

    Ray JG, Berger H, Lipscombe LL, Sermer M. Gestational prediabetes: a new term for early prevention? Indian J Med Res. 2010;132:251–5.

    PubMed  Google Scholar 

  7. 7.

    Kumru P, Arisoy R, Erdogdu E, Demirci O, Kavrut M, Ardıc C, et al. Prediction of gestational diabetes mellitus at first trimester in low-risk pregnancies. Taiwan J Obstet Gynecol. 2016;55:815–20.

    Article  Google Scholar 

  8. 8.

    Mostafavi E, Nargesi AA, Asbagh FA, Ghazizadeh Z, Heidari B, Mirmiranpoor H, Esteghamati A, Vigneron C, Nakhjavani M. Abdominal obesity and gestational diabetes: the interactive role of magnesium. Magnes Res. 2015;28:116–25.

    CAS  PubMed  Google Scholar 

  9. 9.

    Chen H-Y, Cheng F-C, Pan H-C, Hsu J-C, Wang M-F. Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise. PLoS One. 2014;9(1):e85486.

    Article  Google Scholar 

  10. 10.

    Gröber U, Schmidt J, Kisters K. Magnesium in prevention and therapy. Nutrients. 2015;7(9):8199–226

    Article  Google Scholar 

  11. 11.

    Almoznino-Sarafian D, Berman S, Mor A, Shteinshnaider M, Gorelik O, Tzur I, et al. Magnesium and C-reactive protein in heart failure: an anti-inflammatory effect of magnesium administration? Eur J Nutr. 2007;46(4):230–7.

    CAS  Article  Google Scholar 

  12. 12.

    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.

    CAS  PubMed  Google Scholar 

  13. 13.

    Ozgu-Erdinc AS, Yilmaz S, Yeral MI, Seckin KD, Erkaya S, Danisman AN. Prediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices. J Matern Fetal Neonatal Med. 2014;7058:1–6.

    Google Scholar 

  14. 14.

    Syngelaki A, Visser GHA, Krithinakis K, Wright A, Nicolaides KH. First trimester screening for gestational diabetes mellitus by maternal factors and markers of inflammation. Metabolism. 2016;65:131–7.

    CAS  Article  Google Scholar 

  15. 15.

    Zhu C, Yang H, Geng Q, Ma Q, Long Y, Zhou C, et al. Association of Oxidative Stress Biomarkers with gestational diabetes mellitus in pregnant women: a case-control study. PLoS One. 2015;10:e0126490 Hribal ML, editor.

    Article  Google Scholar 

  16. 16.

    Nabouli MR, Lassoued L, Bakri Z, Moghannem M. Modification of Total magnesium level in pregnant Saudi women developing gestational diabetes mellitus. Diabetes Metab Syndr Clin Res Rev. 2016;10:183–5.

    CAS  Article  Google Scholar 

  17. 17.

    Goker Tasdemir U, Tasdemir N, Kilic S, Abali R, Celik C, Gulerman HC. Alterations of ionized and Total magnesium levels in pregnant women with gestational diabetes mellitus. Gynecol Obstet Investig. 2015;79:19–24.

    CAS  Article  Google Scholar 

  18. 18.

    Del Gobbo LC, Song Y, Elin RJ, Meltzer SJ, Egeland GM. Gestational glucose intolerance modifies the association between magnesium and glycemic variables in mothers and daughters 15 years post-partum. Magnes Res. 2012;25:54–63.

    PubMed  Google Scholar 

  19. 19.

    International Association of Diabetes and Pregnancy Study Groups Consensus, Panel MBE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33:676–82.

    Article  Google Scholar 

  20. 20.

    von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344–9.

  21. 21.

    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    CAS  Article  Google Scholar 

  22. 22.

    Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.

    CAS  Article  Google Scholar 

  23. 23.

    Macaulay S, Dunger DB, Norris SA. Gestational diabetes mellitus in Africa: a systematic review. PLoS One. 2014;9(6):e97871.

    Article  Google Scholar 

  24. 24.

    Asemi Z, Karamali M, Jamilian M, Foroozanfard F, Bahmani F, Heidarzadeh Z, et al. Magnesium supplementation affects metabolic status and pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2015;102:222–9.

    CAS  Article  Google Scholar 

  25. 25.

    Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. Failure of beta-cell function for compensate variation in insulin sensitivity in hypomagnesemic subjects. Magnes Res. 2009;22:151–6.

    PubMed  Google Scholar 

  26. 26.

    Yang SJ, Hwang SY, Baik SH, Lee KW, Nam MS, Park YS, et al. Serum magnesium level is associated with type 2 diabetes in women with a history of gestational diabetes mellitus: the Korea National Diabetes Program Study. J Korean Med Sci. 2014;29:84.

    Article  Google Scholar 

  27. 27.

    Hamdan HZ, Nasser NM, Adam AM, Saleem MA, Elamin MI. Serum magnesium, Iron and ferritin levels in patients with diabetic retinopathy attending Makkah eye complex, Khartoum, Sudan. Biol Trace Elem Res. 2015;165(1):30–4.

    CAS  Article  Google Scholar 

  28. 28.

    Shin D, Hur J, Cho E-H, Chung H-K, Shivappa N, Wirth MD, et al. Pre-pregnancy body mass index is associated with dietary inflammatory index and C-reactive protein concentrations during pregnancy. Nutrients. 2017;9(4):E351.

    Article  Google Scholar 

  29. 29.

    Chen X, Scholl TO, Stein TP. Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: the camden study. Diabetes Care. 2006;29:1077–82 Cited 9 Apr 2017.

    CAS  Article  Google Scholar 

  30. 30.

    Rota S, Yildirim B, Kaleli B, Aybek H, Duman K, Kaptanoğlu B. C-reactive protein levels in non-obese pregnant women with gestational diabetes. Tohoku J Exp Med. 2005;206:341–5.

    CAS  Article  Google Scholar 

  31. 31.

    Desoye G, Hauguel-de Mouzon S. The human placenta in gestational diabetes mellitus. The insulin and cytokine network. Diabetes Care. 2007;30(Suppl 2):S120–6.

    CAS  Article  Google Scholar 

  32. 32.

    Vrachnis N, Belitsos P, Sifakis S, Dafopoulos K, Siristatidis C, Pappa KI, et al. Role of adipokines and other inflammatory mediators in gestational diabetes mellitus and previous gestational diabetes mellitus. Int J Endocrinol. 2012;2012:549748.

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Rayis DA, Abbaker AO, Salih Y, Adam I. Obesity and pregnancy outcome in Khartoum, Sudan. Int J Gynecol Obstet. 2011;113(2):160–1.

    Article  Google Scholar 

  34. 34.

    Cruz NG, Sousa LP, Sousa MO, Pietrani NT, Fernandes AP, Gomes KB. The linkage between inflammation and type 2 diabetes mellitus. Diabetes Res Clin Pract. 2013;99(2):85–92.

    CAS  Article  Google Scholar 

Download references


The authors wish to thank the patients who participated in the study for their cooperation and patients.


Not applicable.

Author information




HZH and IA concepted and designed the study. WN, DAR and MAA conducted the study. DAR, MAA, HZH and IA shared in the statistical analyses. WN, HZH and IA share in drafting the paper. All of the authors drafted and approved this version of the paper.

Corresponding author

Correspondence to Hamdan Z. Hamdan.

Ethics declarations

Ethics approval and consent to participate

The study received ethical clearance from Al-Neelain University Research Ethics Review Board in Al-Neelain University, Sudan. All participants provide an informed written consent.

Consent for publication

Not applicable.

Competing interests

One of the authors (Ishag Adam) is a member in BMC Pregnancy and Childbirth editorial board. Other authors declare that they have no competing of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Naser, W., Adam, I., Rayis, D.A. et al. Serum magnesium and high-sensitivity C-reactive protein as a predictor for gestational diabetes mellitus in Sudanese pregnant women. BMC Pregnancy Childbirth 19, 301 (2019).

Download citation


  • Magnesium
  • CRP
  • Pregnancy
  • Insulin resistance
  • Glucose
  • Sudan