Trying to determine modifiable risk factors for gestational diabetes (GDM) is not only beneficial for the mother, but also for protecting the baby; how are vitamin D levels and gestational diabetes connected?
GDM is a common complication of pregnancy affecting both the mother and predisposing childhood complications. Vitamin D deficiency has also been noted as a concern in pregnancy. Trying to hypothesize different mechanisms to determine an association between vitamin D deficiency and the development of GDM has led to trials, but they lack consistent findings.
This study was a prospective, multiracial cohort with three aims, using data from the Fetal Growth Studies-Singleton Cohort. The authors wanted to assess, “the longitudinal trajectories of vitamin D biomarkers over pregnancy, the prospective associations between levels of vitamin D biomarkers during early to mid-pregnancy and subsequent risk of GDM, and whether the levels of vitamin D biomarker from early to MD-pregnancy and their prospective associations with GDM risk are modified by race/ethnicity, prepregnancy body mass index, physical activity, parity, or family history of diabetes.” A total of 321 multiracial pregnant women in the US were included, 107 women with GDM and 214 without (1:2 ratio). Longitudinal maternal blood samples were collected throughout gestation, between weeks 10 to 14, 15 to 26, 23 to 31, and 33 to 39. The samples measured plasma levels of ergocalciferol (D2) and cholecalciferol (D3), plasma vitamin D binding protein (VDBP), plasma albumin, plasma glucose and insulin, and plasma levels of total cholesterol, HDL cholesterol, and triglycerides (further used to calculate LDL). Total 25(OH)D was the sum of measured 25(OH)D2 and 25(OH)D3. Free and bioavailable 25(OH)D were also calculated. Vitamin D deficiency was defined by < 1442 ng/dL (< 50 nmol/L).
Covariates were determined using self-reported questionnaires to collect patient demographics, lifestyle, and medical history. Conventional GDM risk factors were also assessed, counting nulliparity, prepregnancy BMI, and family history of diabetes. The Pregnancy Physical Activity Questionnaire was used to assess physical activity. Linear mixed-effects models and conditional logistic regression models were used to compare data and assess associations.
In both cases and controls, throughout the gestational period, an increase was seen in median levels of 25(OH)D2, 25(OH)D3, and free 25(OH)D. Conversely, a decrease was seen in median bioavailable 25(OH)D levels with the gestational week. Between gestational weeks 10 to 14 up to weeks 15 to 26, there was an increase in median levels of VDBP, followed by a decline until the ending of the pregnancy. In terms of vitamin D biomarkers, no statistically significant differences were seen between the groups.
Significant non-linear associations of total 25(OH)D (P = 0.025) and 25(OH)D3 (P = 0.016) with GDM were noted. Between weeks 10 to 14 (first trimester), after adjusting for potential confounders, vitamin D deficiency was significantly associated with an increased risk of GDM (odds ratio [OR] = 2.82). Comparing those with vitamin D deficiency throughout the first and second trimester (persistent vitamin D deficiency) to those with persistently non-deficient vitamin D levels, they had a higher risk for GDM by 4-fold (OR = 4.46). If women changed from deficient to non-deficient or non-deficient to deficient, this significant association was no longer seen.
Lastly, data from the adjusted mixed-effects models showed statistically different levels of total 25(OH)D and 25(OH)D3 between those with GDM and the non-GDM controls. In the women who developed GDM, lower levels of total 25(OH)D were present at 10 to 14 weeks compared to those without GDM and on a logarithmic scale, had a 6% greater incremental rate of total 25(OH)D levels from 10 to 14 weeks to 15 to 26 weeks (β = 0.06). Furthermore, from the analysis, longitudinal change in the least squares means for a total of 25(OH)D, was significantly greater from 10 to 14 weeks to 15 to 26 weeks (P = 0.046), with similar results for 25(OH)D3. Lastly, the authors stated, with adjustment for race/ethnicity, prepregnancy BMI, maternal age, physical activity, parity, or family history of diabetes, there was no significant effect.
The authors wanted their study to be prospective and longitudinal to show the association between maternal vitamin D levels and the risk of GDM. Their data showed an inverse association between vitamin D in early gestation and the risk of GDM, but also the association during early pregnancy to mid-gestation and its risk for GDM. From the studies, it should be noted that this association shows the importance of assessing vitamin D status throughout gestation. Further studies should be performed with a larger sample to support these current findings. To help progress future testing, a larger sample size should be used to address ethnic disparities fully. Also, in this study parathyroid hormone was not measured and due to its interaction with vitamin D, should be assessed. Future randomized clinical trials are necessary to assess preventative doses and proper therapeutic time windows for supplementation for the prevention of developing GDM.
- Vitamin D deficiency is most crucial during early pregnancy for developing GDM.
- Vitamin D levels should be constantly assessed and treated to prevent the development of GDM.
- Future studies are necessary to determine proper supplementation dosing and therapeutic time windows.
Reference for “The Association Between Vitamin D Levels and Gestational Diabetes”:
Xia, Jin, et al. Vitamin D status during pregnancy and the risk of gestational diabetes mellitus: A longitudinal study in a multiracial cohort. Diabetes Obesity Metabolism. 2019 April 12.
Emma Kammerer, L|E|C|O|M Bradenton School of Pharmacy, PharmD Candidate