Recent literature indicates a high level of incidence of GDM as well as vitamin D deficiency in Saudi Arabia and in this study we aimed to investigate the link, if any, between the two by determining the vitamin D level in the 1st trimester and assessing its association with GDM, determined by performing OGTT in the second semester. In a cohort of 515 pregnant women visiting different hospitals of Riyadh, Saudi Arabia, vitamin D deficiency was detected in 82.5% in the first trimester. On their 2nd visit, during the 2nd trimester of pregnancy, 27.7% of the 419 women who participated in OGTT were diagnosed with GDM. Analysis of the association between vitamin D status and incidence of GDM indicated a 2.87 fold increased risk of development of GDM among vitamin D deficient compared to vitamin D non-deficient women and this risk was sustained or substantially increased when the data was analyzed after adjusting for sunlight exposure, physical activity, calcium and vitamin D intake and other factors that are known to influence vitamin D levels. Of the various anthropometric and biochemical parameters, the GDM women differed significantly from non-GDM women with respect to serum levels of triglyceride, fasting glucose and insulin, among others. Furthermore, all the obesity indices, pre-pregnancy BMI, BMI, waist size, hip size and WHR were significantly higher in the GDM women compared to non-GDM women suggesting a strong confounder effect from obesity. Also, overall, fasting glucose levels determined in the 2nd trimester showed an inverse association with vitamin D levels determined in the 1st semester and while this association was statistically significant it was weak, which may be due to the analysis being performed at different time points. A recent Australian study involving 3393 adults (ages 18–75 years) indicated a direct, protective effect of higher 25(OH)D on fasting plasma glucose and HbA1c, two criteria for assessment of risk of T2DM. Overall, results of our study indicate a significant association between vitamin D deficiency and increased risk of GDM development during the course of pregnancy.

Vitamin D deficiency is common in healthy Saudi adults and is more pronounced in females and especially in the younger age groups [24]. In a recent study performed in Riyadh, the prevalence of vitamin D deficiency (25(OH)D < 50 nmol/l) was high in both premenopausal and postmenopausal groups (80% and 68%, respectively) during the summer, as well as during the winter (85% and 76%, respectively) [25]. Vitamin D deficiency has been reported to be common among pregnant Saudi women living in Riyadh as observed by Al-Farris, recently [26].

The prevalence of GDM varies from 1 to 20%, and is rising worldwide, and the amount of GDM varies in direct proportion to the prevalence of T2DM in a given population, or ethnic group. In a recent retrospective cohort study (2013) involving 3041 women who delivered at King Khalid University Hospital, 569 (18.7%) had GDM [21]. Another study in Saudi Arabia (2015), adopting IADPSG criteria, identified 183 out of a total of 445 women (22.1%) as having GDM [26]. In a prospective cohort study (2015) involving 277 Saudi women who underwent OGTT, 47 (16.9%) were diagnosed by the former American Diabetes Association (ADA) criteria and 115 (41.5%) by the IADPSG criteria, indicating wide difference on the rates of incidence GDM depending on the method adopted. The IADPSG criteria identified all women with GDM by the former ADA criteria and an additional 68 cases [27]. In this context, our results indicating a 30.5% GDM, adopting the IADPSG criteria, may be representative of the current levels of GDM in this region.

The influence of vitamin D on the development of GDM during the course of pregnancy appears uncertain as revealed by the analysis of several individual as well as meta-analysis reports. A meta-analysis of 20 Observational studies that comprised 9209 participants showed that women with vitamin D deficiency experienced a significantly increased risk for developing GDM with a little heterogeneity [28]. A systematic review and meta-analysis of 24 observational studies (2013) found that women with circulating 25(OH)D level < 50 nmol/l in pregnancy experienced an increased risk of preeclampsia and GDM [29]. Also, a systematic review and meta-analysis to study the link between vitamin D and gestational diabetes (2012) indicated a significant inverse relation between serum 25(OH)D and the incidence of GDM and vitamin D deficiency (25(OH)D < 50 nmol/l) in pregnancy was significantly related to the incidence of GDM [30]. However, in a prospective cohort study (Spain, 2015) involving 2382 pregnant women, overall, 31.8% and 19.7% vitamin D insufficiency [25(OH)D3 20–29.99 ng/ml] and deficiency [25(OH)D3 < 20 ng/ml], respectively, showed no association between maternal 25(OH)D3 concentration and risk of GDM [31].

A similar level of uncertainty is suggested by results available from a large number of vitamin D supplementation studies. Meta-analysis (2015) performed on 13 randomized controlled trials (RCTs) (n = 2299) performed to study the effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes concluded that incidence of GDM was not influenced by vitamin D supplementation [32]. This was, despite the increase in circulating 25(OH)D levels that was associated with vitamin D supplementation. However, across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous. A systematic review of seventy-six studies (2014) involving vitamin D supplementation in pregnancy, sponsored by The National Institute for Health (NIH) Research, found considerable heterogeneity between the studies and for most outcomes, including GDM, there was conflicting evidence [33].

High-parity and older age have previously been found to be important risk factors for GDM in the Saudi population [34], where multiparous women were found to be > 8 times increased risk of GDM than nulliparous women. The same study also reported a 2% to 21% increase in GDM incidence when age increased from 20 to 40 years. In addition to high-parity and older age, higher maternal weight was shown to be associated with higher rates of GDM by an earlier study on Saudi women conducted in the 90s [35].

The susceptibility of Saudi women to high rates of GDM may be related to the cultural restrictions on female physical activities that may lead to physical inactivity and increased access to fast foods, both causing obesity. A recent review has shown high prevalence among Saudi women of smoking (up to 9%), hypertension (22%), diabetes (up to 27.6%), overweight (27%), and obesity (40%), and physical inactivity (53.2% to 98.1%), hypercholesterolemia (24.5%) and metabolic syndrome (MetS) (up to 40.3%) [36]. MetS is a cluster of established risk factors that together increase predisposition to major chronic diseases such as heart diseases and diabetes mellitus and a recent study (2014) on adults from several regions of Saudi Arabia confirmed > 28% incidence of MetS [37]. Vitamin D deficiency, a widely prevalent condition in Saudi Arabia, has been cited to be associated with MetS in several cross-sectional studies involving middle-aged East Asians and Europeans, but not in multicultural populations of United States and New Zealand [38]. Our results may mean that MetS is a converging point of vitamin D deficiency and obesity related issues eventually leading to increased rates of GDM in Saudi Arabian women.

A consistent association between the obesity levels, as determined from BMI and other indices, and GDM observed in this study suggests a confounding role from obesity. Altogether, results from our study performed on women living in a region which is reported to have high rates of obesity and T2DM, in general, clearly indicate a 2.8-fold increased risk among women who are vitamin D deficient.