Introduction

Gestational diabetes mellitus (GDM) is characterized as glucose intolerance during pregnancy and includes about 7% (1-14%) of pregnancies¹. Vitamin D deficiency has been considered as a risk factor for glucose intolerance for a long time². In some studies, a correlation has been observed between low vitamin D levels and maternal glycemia, insulin resistance and risk of diabetes³. However, the exact association of vitamin D levels and diabetes risk still remains unclear. Different studies have also indicated that maternal low serum vitamin D levels may intensify the medical complications for both mother and fetus during pregnancy⁴. Moreover, low serum vitamin D levels has been reported in pregnant women with GDM which is usually associated with preeclampsia, GDM, infertility and increased probability of cesarean delivery⁵. Vitamin D also modulates the immune system, cytokines and anti-bacterial peptides and the use of this vitamin is considered as an important medical care during pregnancy⁶. For instance, increased risk of maternal human immune deficiency virus (HIV) transmission and fetal mortality have been observed in pregnant women with HIV⁷. Low vitamin D levels have also been associated with bacterial vaginoses during the first trimester⁸. Epidemiological studies have also reported low levels of this vitamin during pregnancy in different populations.

Several mechanisms have been proposed for low vitamin D levels and increased risk of GDM: i) the active form of vitamin D (1,25 (OH) vitamin D) by interaction with its receptor on pancreases β-cell can regulate the secretion pattern of these cells via intra or extracellular calcium balancing. ii) Vitamin D can increase the insulin sensitivity by insulin receptor overexpression and glucose transfer. iii) Vitamin D by regulating the extracellular calcium levels and transmembrane calcium transfer facilitation into intracellular matrix, provides a sufficient intracellular source for the insulin-dependent processes in insulin-responding tissues^9-11.

Regarding the above information, this study aimed to compare the vitamin D serum levels in pregnant women with or without GDM.

Materials and Methods:

Patients

Eighty pregnant women (40 with GDM and 40 healthy controls) were enrolled in this descriptive cross-sectional study. Glucose tolerance test (GTT) was performed after 8 hours fasting using 75 gram glucose within 24-28 pregnancy weeks. The criteria for GDM diagnosis were fasting blood glucose (FBG) ≥92 mg/dl or 1 hour postprandial (1hpp) ≥180 mg/dl or 2hpp ≥153 mg/dl. The serum levels of 25(OH) vitamin D, calcium, phosphorous. Additionally, the serum levels of vitamin D was categorized in three groups as sufficient (30-100 ng/ml), insufficient (20-30 ng/ml) and deficiency (≤20 ng/dl). This study was approved by the local ethics committee of Bushehr University of Medical Sciences, Bushehr, Iran. Written informed consent was obtained from all participants prior the sampling.

Statistical analysis

Data were analyzed using Statistical Package for the Social Sciences (SPSS) 23. Kolmogorov-Smirnov (K-S) test was used to assess the normality of the quantitative parameters. Independent T-test was also used for the comparison of the quantitative parameters mean between groups. Logistic regression test was used to adjust the age effect. P<0.05 was considered as statistically significant.

Results:

General characteristics of the patients and biochemical parameters are presented in Table 1. Statistical significant differences were observed in age (p=0.017) and FBG (p=0.001) between studied groups. No significant statistical differences were observed in the remaining parameters between groups.

According to table 2, 35 (87.5%) and 30 (75%) of the diabetic and non-diabetic pregnant women had 25 (OH) vitamin D levels <20 ng/dl which showed no significant statistical differences (p=0.025). In individuals with 25 (OH) vitamin D ≥20 ng/dl no significant statistical differences were also observed between studied groups (p=0.31).

Table 3 also represents the diabetes odds ratio (OR) regarding the 25 (OH) vitamin D levels. As it is shown, the risk of diabetes was 2.44 fold higher in patients with 25 (OH) vitamin D levels <20 ng/ml. However this difference was not statistically significant (p=0.15).

Discussion

In the present study, 35 (87.5%) and 30 (75%) of the pregnant women were diabetic and non-diabetic, respectively which had 25 (OH) vitamin D levels less than 20 ng/ml. However, no significant statistical differences were observed between groups. In a study conducted by Farrant H.J et al on 599 pregnant women with GDM in India, similar results were observed and no correlations were found between low vitamin D levels and GDM¹². In another study by Rodriguez A. et al. on 2382 Spanish pregnant women, no associations were also found between 25 (OH) vitamin D levels and the risk of GDM¹³. Rodriguez A. et al study on 524 pregnant women also revealed similar results¹⁴. Clifton et al., in a cohort study in England and Australia also reported a reverse correlation between maternal vitamin D levels and FBS and insulin levels. However, the risk of GDM was not significantly increased in response to the low levels of vitamin D. The main limitation of the Clifton et al. study was targeting the pregnant women referring to the pregnancy clinics for any reason for performing blood tests specially GTT. Therefore, this study has mainly targeted the women at the risk of GDM and the other women at the risk were not evaluated. Additionally, this study was not applicable for the women with low glucose intolerance risk¹⁵.

In another study by Makgoba et al. on 248 pregnant women (90 with GDM and 158 healthy controls), no correlations were observed between 25 (OH) vitamin D levels and the risk of GDM in the first trimester¹⁶.

In contrast, Zhang et al in a study on 953 pregnant women showed a significant decreased 25 (OH) vitamin D levels in women with GDM compared to healthy controls. This study also has indicated the higher risk of GDM in pregnant women with vitamin D deficiency in the first pregnancy¹⁷. Moreover, Parlea et al. in a study on 335 patients reported an increased risk of GDM in vitamin D deficient individuals¹⁸.

Ghiu et al. also reported a significant correlation between vitamin D deficiency and the increased risk of GDM. In this study, 20 GDM patients and 40 healthy pregnant women were enrolled. Data revealed vitamin D deficiency in 27% and 85% of healthy controls and GDM patients, respectively. Additionally, the vitamin D levels were significantly lower in GDM patients compared to the healthy controls. However, small sample size and cross-sectional data can make the results interpretation difficult¹⁹.

Regarding the controversial results of our study with the other studies and the small sample size, further prospective studies with larger sample size is recommended.

Conflict of interest: All authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Ethical approval

The study protocol was approved by the Ethics Committee of Bushehr University of Medical Sciences, Bushehr, Iran. The current study was performed according to the Institutional Committee for the Protection of Human Subjects, which was adopted by the 18th World Medical Assembly, Helsinki, Finland and its later amendments.

Acknowledgments

Acknowledgments: This study was financially supported by Bushehr University of Medical sciences.

References

1. Melchior H, Kurch-Bek D, Mund M. The prevalence of gestational diabetes: a population-based analysis of a nationwide screening program. Deutsches Ärzteblatt International. 2017 Jul;114(24):412.

2. Barret H,McElduff A. Vitamin D and Pregnancy: An old problem revisited.Best Pract Res Clin Endocrinol Metab 2010; 24(4):527-539.

3. Soheilykhah S,Mojibian M,Rahimi-Saghand S,Jafari F. Maternal vitamin D status in gestational diabetes mellitus.Nutr Clin Pract 2010;25(5):524-7

4. Palomer X, González‐Clemente JM, Blanco‐Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes, Obesity and Metabolism. 2008 Mar;10(3):185-97.

5. Baker AM,Haeri S,Camarqo CA,et al. First-trimester maternal vitamin D status and risk for gestational diabetes(GDM)a nested case-control study.Diabetes Metab Res Rev 2012;28(2):164-8

6. Mathieu C, van Etten E, Decallonne B, Guilietti A, Gysemans C, Bouillon R, Overbergh L. Vitamin D and 1, 25-dihydroxyvitamin D3 as modulators in the immune system. The Journal of steroid biochemistry and molecular biology. 2004 May 1;89:449-52.

7. Perez-Ferre N, Torrejon M, Fuentes M, Fernandez M, Ramos A, Bordiu E. Association of low serum 25-hydroxyvitamin D levels in pregnancy with glucose homeostasis and obstetric and newborn outcomes. Endocrine Practice. 2012 May 1;18(5):676-84.

8. Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. The Journal of nutrition. 2009 Jun 1;139(6):1157-61.

9. Aminian K, Bahrami A, Najafipour M, Najafipour F. Effect of Vitamin D Replacement on Serum TSH in Women with Anti-TPO Positive Sub-clinical Hypothyroidism. Journal of Clinical & Diagnostic Research. 2019 Jan 1;13(1).

10. Brooke OG, Butters F, Wood C. Intrauterine vitamin D nutrition and postnatal growth in Asian infants. British medical journal (Clinical research ed.). 1981 Oct 17;283(6298):1024.

11. Vosoughi A, Aliasgarzadeh A, Bahrami A, Abbasalizadeh F, Niafar M, Najafipour F. Concentration of maternal serum 25-hydroxy Vitamin D and gestational 2 diabetes mellitus risk. Pharmaceutical Sciences. 2017 Sep 1;23(3):189-92.

12. Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. European journal of clinical nutrition. 2009 May;63(5):646.

13. Rodrıguez-Martınez MA, Garcıa-Cohen EC. Role of Ca2+ and vitamin D in the prevention and treatment of osteoporosis. Pharmacology & Therapeutics. 2002 Jan 1;93(1):37-49.

14. Rodriguez A, García‐Esteban R, Basterretxea M, Lertxundi A, Rodríguez‐Bernal C, Iniguez C. Associations of maternal circulating 25‐hydroxyvitamin D3 concentration with pregnancy and birth outcomes. BJOG: An International Journal of Obstetrics & Gynaecology. 2015 Nov;122(12):1695-704.

15. Clifton-Bligh RJ, McElduff P, McElduff A. Maternal vitamin D deficiency, ethnicity and gestational diabetes. Diabet Med 2008; 25:678–84.

16. Makgoba M, Nelson SM, Savvidou M, Messow CM, Nicolaides K, Sattar N. First-trimester circulating 25-hydroxyvitamin D levels and development of gestational diabetes mellitus. Diabetes care. 2011 May 1;34(5):1091-3.

17. Zhang C, Qiu C, Hu FB, David RM, Van Dam RM, Bralley A. Maternal plasma 25-hydroxyvitamin D concentrations and the risk for gestational diabetes mellitus. PloS one. 2008 Nov 18;3(11):e3753.

18. Parlea L, Bromberg IL, Feig DS, Vieth R, Merman E, Lipscombe LL. Association between serum 25‐hydroxyvitamin D in early pregnancy and risk of gestational diabetes mellitus. Diabetic Medicine. 2012 Jul;29(7):e25-32.

19. Chiu KC, Chu A, Go VLW, and Saad MF. Hypovitaminosis D is associated with insulin resistance and T cell Dysfunction. Am J Clin Nutr 2004; 79: 820 –5.

Author notes

Farzadnajafipour@gmail.com