Interpretation (In light of other evidence)
In our large cohort, the 1st trimester median FPG level was 82 (78-87) mg/dl. Riskin-Mashiah et al. evaluated the FPG level throughout pregnancy and demonstrated a mean 3 mg/dl decrease in early pregnancy compared to the preconception state (from 81 to 78 mg/dl) 11. The same group reported in 2009 that increased FPG levels at early pregnancy, even within normal levels, were correlated with increased adverse pregnancy outcomes12. Our study findings are consistent with this pattern, showing a similar relationship between increasing 1st trimester FPG levels and the risk of developing T2DM in the future, paralleling the observed association with perinatal outcomes.
Our study demonstrated an increased risk for T2DM according to 1st trimester FPG levels within the normal non-diabetic range. Our results are in line with previous studies that evaluated FPG levels and risk for T2DM in the general population13,14 and young men 15. For example, in alignment with our results, Tirosh et al. reported that FPG levels exceeding 87 mg/dl were linked to an increased risk of future T2DM in a cohort of 40,000 young adult males, even after accounting for multiple T2DM risk factors 15.Other studies performed in the general population suggested a cut-off level of 94 mg/dl as an optimal point of specificity and sensitivity for predicting T2DM13,14. We can assume that the decrease in FPG levels, which is suggested in early pregnancy compared to preconception11, as well as other differences in the cohort’s basic characteristics, may account for these differences in cut-offs. Furthermore, Specifically to pregnancy, a recently published study had shown that women with glucose intolerance during pregnancy, even if it did not meet the standard GDM criteria, had an increased risk of T2DM in young adulthood 16. Moreover, they observed comparable risks of developing T2DM among women with GDM and normal FPG levels and those with isolated abnormal gestational FPG. It is worth noting that in contrast to our study, the FPG level in that study was documented as part of oGTT and not during early pregnancy 16.
The recently published TOBOGM study 17 is a randomized controlled study explored immediate intervention for early GDM or deferred intervention, according to oGTT results at 24-28 gestational weeks, and perinatal outcomes. Early GDM was defined by the IADPSG as 1st trimester fasting glucose of 92-125 md/dl6. The study suggested that early intervention for early GDM led to a modest improvement in composite neonatal outcomes17. However, the study evaluated only women with risk factors for GDM and did not include maternal or offspring long-term outcomes.