Hormonal
Carriage of rare, potentially deleterious variants in the GLP1R gene is associated with an increased risk of Type 2 Diabetes (T2D) and higher HbA1c levels, particularly in individuals with obesity.
If you have a family history of T2D and carry rare GLP1R variants (often identified through specialized genetic testing), maintaining a healthy weight is critically important. This paper shows that the genetic risk for diabetes is significantly amplified if you are obese. Weight management is not just general advice but a specific counter-measure for this genetic profile.
gene-level analysis of the UKB exome sequence dataset (629/39,274 carriers) confirmed that rare GLP1R variants are associated with increased risk of T2D (OR=1.58), as well as with higher HbA1c levels (p= 0.039)... the effect of GLP1R variant carriage on T2D status was statistically significant only in individuals who had obesity (OR = 1.60... p = 6.8x10-4 for CADD 15; OR =2.09... p = 1x10-4 for CADD 20).
Why this rating
The study uses large-scale biobank data (UK Biobank) but relies on genetic association (observational) rather than randomized controlled trials of interventions, and acknowledges limited statistical power for rare variants.
Source
Rare variants of the glucagon-like peptide-1 receptor (GLP1R) gene are overrepresented in a severe obesity cohort and associated with type 2 diabetes in the UK Biobank
Dale Handley et al. · medRxiv · 2023
DOI 10.1101/2023.05.22.23290347
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