The influence of FTO and ADRB2 gene polymorphisms on pregestational BMI and gestational weight gain in women with diabetes mellitus: Results of a randomized nutrigenetic trial

Background and objectives: Obesity and diabetes mellitus (DM) are multifactorial diseases that increase the risk of adverse outcomes of pregnancy. We investigated the influence of FTO (rs9939609 / rs17817449) and ADRB2 (rs1042713 / rs1042714) gene polymorphisms on pregestational BMI and gestational weight gain (GWG) in pregnant women with DM. Methods: The study was conducted in a public hospital at Rio de Janeiro/Brazil (2016-2020). Seventy pregnant women with pregestational DM were randomly assigned at the beginning of prenatal care to one of the nutritional intervention groups: traditional diet (a healthy Brazilian dietary pattern) or DASH diet (Dietary Approach to Stop Hypertension), until the childbirth. Pregestational BMI was calculated as pre-pregnancy weight/height². Excessive GWG was the total weight gain above the upper limit of the Institute of Medicine recommendations. Genotyping was performed using real-time PCR. Medians were compared using non-parametric tests. Time-to-event analysis was performed to investigate the risk for progression to excessive GWG. Results: Participants had 32 (IQR 25.7 – 36.0) years old, 51.4% had type 1 DM. Pregestational BMI was 27.8 kg/m² (IQR 24.4 – 32.3). All women with GG genotype for rs1042714 had type 1 DM and lower pregestational BMI than the CG or CC carriers (23.3 kg/m² [20.1 – 26.4] vs. 28.0 kg/m² [24.6 – 32.4]; p= 0.02). The other polymorphisms evaluated had similar distribution between the types of DM and were not associated with pregestational BMI. There was no difference in GWG between diet groups, 52.9% of women had excessive GWG. Regardless the dietary pattern or DM type, AT carriers of rs9939609 (FTO) and AA carriers of rs1042713 (ADRB2) had higher risk of earlier exceeding GWG compared to TT (aHR 2.4; CI 95% 1.0–5.8; p = 0.04) and GG (aHR 3.9; CI 95% 1.1–13.7; p = 0.03) genotypes, respectively, as the AG carriers for FTO haplotype rs9939609:rs17817449 compared to TT carriers (aHR 1.8; CI 95% 1.0–3.1; p = 0.02). Conclusions: FTO and ADRB2 gene polymorphisms influenced maternal body weight. It may be considered hereafter to investigate personalized nutrition with potential to protect maternal and child health in pregnancies affected by DM.