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GLP-1R Polymorphisms Modify the Relationship Between Exposure to Gestational Diabetes Mellitus and Offspring BMI
Kylie K Harrall1,2,3, Deborah H Glueck4, Leslie A Lange3,5
1Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus, Aurora, CO.
Diabetes Care
|May 30, 2025
Summary
Gestational diabetes mellitus (GDM) exposure affects childhood BMI trajectories. Specific glucagon-like peptide 1 receptor gene (GLP-1R) polymorphisms influence this association, impacting offspring BMI growth but not glucose-insulin homeostasis markers.
Area of Science:
- Genetics and Developmental Biology
- Pediatric Endocrinology
- Metabolic Health
Background:
- Maternal gestational diabetes mellitus (GDM) is linked to elevated childhood body mass index (BMI).
- The glucagon-like peptide 1 receptor gene (GLP-1R) plays a role in metabolic regulation.
- Understanding genetic influences on offspring metabolic health following GDM exposure is crucial.
Purpose of the Study:
- To investigate if specific GLP-1R gene polymorphisms modify the relationship between maternal GDM exposure and childhood BMI trajectories.
- To determine if GLP-1R polymorphisms influence markers of glucose-insulin homeostasis in adolescents exposed to GDM in utero.
Main Methods:
- Analysis of 464 participants from the Exploring Perinatal Outcomes Among Children (EPOCH) study.
- Microarray genotyping for GLP-1R polymorphisms (rs10305420, rs1042044, rs6923761) in childhood.
- Characterization of BMI trajectories and assessment of glucose-insulin homeostasis markers in adolescence.
Main Results:
- GLP-1R polymorphisms rs10305420 and rs1042044 modified the GDM-BMI association; minor allele carriers exposed to GDM had higher average BMI.
- For rs6923761, GDM-exposed individuals with the GG genotype showed significantly higher average BMI.
- No GLP-1R polymorphisms altered the association between GDM exposure and adolescent glucose-insulin homeostasis markers.
Conclusions:
- GLP-1R gene polymorphisms play a significant role in modulating the impact of maternal GDM on offspring BMI growth.
- These genetic variations contribute to heterogeneity in offspring BMI trajectories following GDM exposure.
- Further research is warranted to confirm these findings and elucidate the underlying biological mechanisms.
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