Aim
Genetic variants associated with gestational diabetes mellitus (GDM, n=14 SNPs) were recently classified into two groups: type 2 diabetes predominant effects (Class-T, three SNPs) and GDM-predominant effects (Class-G, eight SNPs; three SNPs unclassified). We aimed to compare the effects of GDM-associated variants on glucose levels (fasting glucose and 2-hour post-OGTT) measured during versus post pregnancy.
Research design and Methods
We calculated genetic scores (GS) by class (T_GS and G_GS) and overall (All_GS) in 10 225 pregnant women and 4763 women post pregnancy (mean 10.5 years post pregnancy) from eight datasets representing four ancestrally-diverse cohorts: Exeter Family Study of Childhood Health, Genetics of Glucose Regulation in Gestation and Growth, Hyperglycaemia and Adverse Pregnancy Outcome, and Finnish Gestational Diabetes. We used linear regression models adjusted for ancestry principal components to investigate associations between standardized GS and glucose levels during or post pregnancy. Analyses were performed separately in each dataset and then combined using inverse-variance weighted random-effects meta-analyses.
Results
All_GS was associated with fasting glucose both during and post pregnancy (β (95% CI), in mmol/L per 1 SD higher GS=0.06 (0.04 to 0.08) during vs 0.06 (0.04 to 0.07) post pregnancy). All_GS was also associated with 2-hour post-OGTT glucose levels during pregnancy but not after (0.10 (0.04 to 0.15) during vs 0.01 (–0.04 to 0.07) post pregnancy). Both G_GS and T_GS showed consistent associations with fasting glucose during and post pregnancy (0.06 (0.04 to 0.08) during and 0.05 (0.03 to 0.07) post pregnancy for G_GS; 0.02 (0.01 to 0.02) during and 0.02 (–0.001; 0.05) post pregnancy for T_GS). G_GS showed weak evidence of association with 2-hour glucose levels during pregnancy (0.06 (–0.002 to 0.11)) and no association with 2-hour glucose levels post pregnancy (–0.03 (–0.08 to 0.03)). However, T_GS was associated with 2-hour glucose during pregnancy and post pregnancy (0.10 (0.04 to 0.16) and 0.06 (0.01 to 0.12)).
Conclusion
Consistent associations with fasting glucose levels during and after pregnancy may suggest that biological pathways underlying GDM genetic susceptibility to fasting hyperglycemia are not pregnancy specific. However, the results for All_GS and 2-hour glucose provide evidence that some genetic associations with postprandial glucose may be stronger in pregnancy and should be followed up in larger samples.
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