Vitamin D plays a great role in bone metabolism and mineral homeostasis. Relevant data identify roles for the active form of vitamin D (1,25(OH)2D3) in many biological processes including regulation of cellular growth, differentiation and metabolic modulations [8]. Vitamin D insufficiency has a known effect on bone density, neonatal vitamin D and calcium status, and childhood rickets [9]. In several studies, the relation between low vitamin D levels, insulin resistance and impaired insulin secretion was clearly demonstrated [10]. Moreover, specific receptors for 1,25(OH)2D3 were detected in pancreatic ß cells, denoting a probable effect of vitamin D on the insulin secretion process [11]. Obesity is another significant risk factor for 25OHD deficiency [12, 13]. An analysis of the National Health and Nutrition Examination Survey (NHANES) for the years 2003/2004 data also demonstrated that 25 (OH) D deficiencies were highly prevalent in overweight and obese American subjects [14].
In our study we tried to find a correlation between glycemic control and vitamin D deficiency in pregnant women known to have gestational diabetes, diagnosed at previous visits, and we included normal pregnant population as a control. Vitamin D deficiency was the salient feature in both groups, with the mean serum vitamin D levels close in both groups. This could be explained by the fact that the great majority of the pregnant women, included in our study, belonged to poor economic standards which may affect a good supplementation of vitamin D; they have poor housing conditions, poor exposure to sun, insufficient food intake which might be referred to as vegetarian in other papers, repeated non spaced pregnancies and lack of medical service to provide good vitamin supplementation. Another important factor is that, in spite of the sunny climate in Egypt, all the included women were veiled, which hinder the passage of sunrays to the skin, and subsequently diminishing trans-cutaneous vitamin D absorption. We had a negative linear correlation between fasting blood glucose levels and vitamin D3. Our findings also support an independent inverse association between 25(OH)D and HbA1c in women with GDM, showing a potential interaction between 25(OH)D and blood glucose control in pregnancy. The higher levels of HbA1c, indicating poor glycemic control, were found in women with lower levels of 25(OH)D and this inverse relation was found to be statistically significant (r = - 0.492).
The possible explanation for such relationship, between Vitamin D deficiency and the impaired glycemic control, found in our study could be made attributed to the defect in the important role that Vitamin D plays in glucose homeostasis, and via different mechanisms. The mechanism of action of vitamin D in type 2 diabetes is thought to be mediated not only through regulation of plasma calcium levels, which regulate insulin synthesis and secretion, but it also improves insulin sensitivity of the target cells (liver, skeletal muscle, and adipose tissue). Additionally, Vitamin D enhances and improves β-cell function and protects them from detrimental immune attacks, directly by its action on β-cells, but also indirectly by acting on different immune cells, including inflammatory macrophages, dendritic cells, and a variety of T cells. Macrophages, dendritic cells, T lymphocytes, and B lymphocytes can synthesize Vitamin D, all contributing to the regulation of local immune responses [15].
This correlation between vitamin D and GDM were evaluated by various studies and the results were controversial [16–19]. Maghbooli et al demonstrated that maternal serum levels of 25(OH)D during 24-28 weeks of pregnancy were significantly lower in women with GDM compared with controls [16]. More recently, Makgoba and his colleagues did not find an association between first trimester maternal serum 25(OH)D levels and subsequent GDM development [17]. On the other way round, Clifton-Bligh demonstrated an inverse association between maternal serum 25(OH)D levels and fasting blood glucose, although the association between 25(OH)D and GDM was not statistically significant [18]. Additionally, a recent study of Indian women failed to demonstrate a relationship between maternal vitamin D status and risk of developing GDM [19]. More recently meta-analysis, published in 2013, linked gestational diabetes with insufficient 25(OH)D levels, it correlated in addition vitamin D deficiency to preeclampsia, preterm birth and small for gestational age (SGA) babies [20]. In 2013, a randomized controlled study from a Turkish group, on 234 women with GDM and 168 controls, came to a more specific conclusion; they found a statistical significance, between glycemic control and vitamin D levels, only in women with severe deficiency of 25(OH)D levels. They also concluded that only this group (with severe vitamin D deficiency) is at a higher risk of GDM [21]. We mostly attribute this disparity in the results and correlations to the population differences, the most influential factor being, from our point of view, the absence or very few numbers of pregnant women with severely deficient 25OHD.
An important limitation of the present study is the small number of patients with severe vitamin D deficiency and the single measurement of 25(OH)D levels in the third trimester of pregnancy. Other confounding factors included the seasonal variation, as the study extended over a whole year, the heterogeneity of dietary habits and the differences in socioeconomic standards between the included pregnant women. We believe however that these factors did not have a major impact on the statistical analysis of this study, considering that most, if not all, of our patients live in the poor socioeconomic areas.