Examining the impact of gestational diabetes genetic susceptibility variants on maternal glucose levels during and post pregnancy

Cissé, AH; Kuang, A; Allard, C; Ronkainen, J; Beaumont, RN; Sebert, S; Scholtens, DM; Hattersley, AT; Vääräsmäki, M; Kajantie, E; Bouchard, L; Perron, P; Keikkala, E; Hivert, MF; Lowe, WL; Hughes, AE; Freathy, RM

doi:10.1136/bmjdrc-2025-005382

Gestational diabetes & diabetes in pregnancy

Examining the impact of gestational diabetes genetic susceptibility variants on maternal glucose levels during and post pregnancy

BMJ Open Diabetes Res CarePublished 3 Dec 2025Genetic association study with meta-analysis of cohorts

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Authors' 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.

Study context

Population: Pregnant and post-pregnancy women from Exeter Family Study of Childhood Health, Genetics of Glucose Regulation in Gestation and Growth, Hyperglycaemia and Adverse Pregnancy Outcome, and Finnish Gestational Diabetes cohortseight datasets
Participants: 10,225 vs 4,763

Comparison: Gestational diabetes mellitus (GDM) genetic scores and glucose levels during vs post pregnancy
During pregnancyn = 10,225
Post pregnancyn = 4,763
Outcome: Association of standardized GDM genetic scores with fasting glucose and 2-hour post-OGTT glucose

Methodological detailsfour ancestrally-diverse cohorts, eight datasets, linear regression adjusted for ancestry principal components, inverse-variance weighted random-effects meta-analysis

Four ancestrally-diverse cohorts
Eight datasets
Linear regression adjusted for ancestry principal components
Inverse-variance weighted random-effects meta-analysis

Pooled result

As reported in the abstract

Fasting glucose, All_GS (β in mmol/L per 1 SD higher GS)

During pregnancy0.06β · 95% CI 0.04–0.08 · mmol/L per 1 SD higher GS

Post pregnancy0.06β · 95% CI 0.04–0.07 · mmol/L per 1 SD higher GS

Further pooled results

2-h post-OGTT glucose, All_GS (β per 1 SD higher GS)

During pregnancyβ 0.10 mmol/L per 1 SD higher GS95% CI 0.04–0.15

Post pregnancyβ 0.01 mmol/L per 1 SD higher GS95% CI −0.04–0.07

Fasting glucose, G_GS (β per 1 SD higher GS)

During pregnancyβ 0.06 mmol/L per 1 SD higher GS95% CI 0.04–0.08

Post pregnancyβ 0.05 mmol/L per 1 SD higher GS95% CI 0.03–0.07

Fasting glucose, T_GS (β per 1 SD higher GS)

During pregnancyβ 0.02 mmol/L per 1 SD higher GS95% CI 0.01–0.02

Post pregnancyβ 0.02 mmol/L per 1 SD higher GS95% CI −0.001–0.05

2-h glucose, T_GS (β per 1 SD higher GS)

During pregnancyβ 0.10 mmol/L per 1 SD higher GS95% CI 0.04–0.16

Post pregnancyβ 0.06 mmol/L per 1 SD higher GS95% CI 0.01–0.12

Outcome	During pregnancy	Post pregnancy
2-h glucose, G_GS (β per 1 SD higher GS)	β 0.06 (95% CI −0.002–0.11) mmol/L per 1 SD higher GS	β −0.03 (95% CI −0.08–0.03) mmol/L per 1 SD higher GS

2-h post-OGTT glucose, All_genetic scores (GS) (β per 1 SD higher GS)

Associated during pregnancy but not after

2-h glucose, G_GS (β per 1 SD higher GS)

Weak evidence of association during pregnancy; no association post pregnancy

Original publication

Examining the impact of gestational diabetes genetic susceptibility variants on maternal glucose levels during and post pregnancy. BMJ Open Diabetes Res Care. Published 3 December 2025. doi:10.1136/bmjdrc-2025-005382

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