Abstract P266: Biomarkers of Vitamin D3 C-3 Epimers During Pregnancy and the Risk of Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort
Authors: Xia Jin , Song Yiqing , Wu Jing , Hinkle Stefanie , Li Mengying , Tsai Michael Y , Zhang Cuilin 
Published: March 2019

Introduction:
Recent evidence suggests that the C-3 epimer of 25 hydroxyvitamin D3 [3-epi-25(OH)D3] is detectable in a variety of populations and correlates with 25(OH)D3. However, little is known on its status across different trimesters of pregnancy and its pre-diagnostic value in predicting risk of gestational diabetes (GDM).

Hypothesis:
We aimed to determine whether lower levels of 3-epi-25(OH)D3 during early to mid-pregnancy were associated with higher risk of developing GDM.

Methods:
We conducted a nested case-control study of 107 GDM cases and 214 matched controls within the NICHD Fetal Growth Studies-Singleton Cohort (2009-2013). Plasma concentrations of 3-epi-25(OH)D3 [limit of detection (LOD) = 2.25 nmol/L (0.9 ng/mL)] and 25(OH)D3 were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39. The LOD/√2 substitution method was applied to impute the non-detects. Relative C-3 epimer contribution [i.e., the percentage of total 25(OH)D3 accounted for by 3-epi-25(OH)D3] was calculated as: [3-epi-25(OH)D3/(3-epi-25(OH)D3+25(OH)D3)] * 100. Linear mixed-effects models and conditional logistic regression models were used to assess the associations of longitudinal change of 3-epi-25(OH)D3 with GDM risk after adjusting for conventional GDM risk factors.

Results:
Overall, approximately 75.1% of participants had detectable 3-epi-25(OH)D3 ranging from 2.41-22.43 nmol/L and relative C-3 epimer contribution ranged from 2.55%-19.76%. While median concentrations of 3-epi-25(OH)D3 increased slightly with gestational ages throughout pregnancy, relative C-3 epimer contribution decreased from GWs 10-14 to GWs 15-26 with a subsequent increase until the end of gestation among both cases and controls. There were no significant differences between GDM cases and controls in C-3 epimer (median: 4.48 vs. 4.56 nmol/L) or in relative C-3 epimer contribution (5.68% vs. 5.76%) during the first two study visits (all P > 0.05). After imputation, we consistently observed no associations of 3-epi-25(OH)D3 (GWs 10-14, OR
adj
= 0.90, 95% CI: 0.59-1.37; GWs 15-26, OR
adj
= 1.05, 95% CI: 0.64-1.71) or the relative C-3 epimer contribution (GWs 10-14, OR
adj
= 1.39, 95% CI: 0.95-2.04; GWs 15-26, OR
adj
= 1.36, 95% CI: 0.90-2.06) with GDM. Overall, there was no significant difference in longitudinal change of 3-epi-25(OH)D3 and the relative C-3 epimer contribution between cases and controls from GWs 10-14 weeks to 15-26 weeks (all P ≥ 0.09). In addition, we observed no significant joint association between 3-epi-25(OH)D3 and total 25(OH)D with GDM risk at either GWs 10-14 or GWs 15-26.

Conclusions:
Our longitudinal study showed that early and mid-pregnancy biomarkers of 3-epi-25(OH)D3, independently or jointly with total 25(OH)D3, were not associated with GDM risk in US women. Our findings do not support potential clinical usefulness of 3-epi-25(OH)D3 biomarkers in predicting GDM risk.