GLP-1R Gene Polymorphisms and Metabolic Traits During Childhood and Adolescence: The EPOCH Study
Authors' conclusion
GLP-1R polymorphisms are associated with faster BMI growth across development, and lower estimated insulin sensitivity and higher compensatory insulin secretion during adolescence. GLP-1R polymorphisms should be considered in future pediatric studies of genetic susceptibility for obesity and diabetes.
Study context
- Population
- Youth (childhood and adolescence), EPOCH Study; GLP-1R polymorphisms rs10305420, rs6,923,761 and rs1,042,044
- Exposure
- Major-allele homozygotes (rs10305420 CC, rs6923761 GG) vs minor allele carriers of 3 GLP-1R polymorphisms
- Outcome
- Body mass index (BMI) trajectories and markers of glucose-insulin homeostasis (oral glucose tolerance test (OGTT) glucose and insulin, HOMA2-IR, insulinogenic index, HOMA2-%B, oral disposition index)
Methodological detailsEPOCH cohort, mixed models, linear models
- EPOCH cohort
- Mixed models
- Linear models
Main finding
As reported in the abstract
BMI growth
rs6923761 GG vs Minor allele carriersDifference in BMI velocity, /year (95% CI)
At age 10; faster with GG
0.16(0.07–0.24)
rs6923761 GG vs Minor allele carriersAverage difference in BMI (95% CI)
By age 16; higher with GG
1.29(0.22–2.37)
Observational data: associations, not effects.
Further findings
| Outcome | Estimate |
|---|---|
| HOMA2-IRrs10305420 CC vs Minor allele carriers · higher with CC | β 1.19 % (95% CI 1.06–1.32) |
| HOMA2-IRrs6923761 GG vs Minor allele carriers · higher with GG | β 1.13 % (95% CI 1.01–1.26) |
| HOMA2-%B and stimulated insulin secretion (OGTT)rs10305420 CC vs Minor allele carriers · higher with CC | β (HOMA2-%B) 1.09 % (95% CI 1.01–1.17) |
| HOMA2-%B and stimulated insulin secretion (OGTT)Between rs10305420 CC and Minor allele carriers · estimate outside printed CI | β (insulin at 30 minutes) 27.62 μIU/mL (95% CI 3.00–25.24) |
| HOMA2-%B and stimulated insulin secretion (OGTT)rs10305420 CC vs Minor allele carriers · higher with CC | β (insulin at 120 minutes) 18.94 μIU/mL (95% CI 1.04–36.84) |
Original publication
GLP-1R Gene Polymorphisms and Metabolic Traits During Childhood and Adolescence: The EPOCH Study. J Clin Endocrinol Metab. Published 18 December 2024. doi:10.
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