Methods: We used a multidisciplinary approach encompassing population genomics and a clinical randomized trial.
Results: We constructed genetic risk scores (GRS) for IR and systolic blood pressure (SBP) and, using the GoDARTS study which consists of over 10 000 patients with diabetes and over 8000 controls, found that IR and SBP GRS were significantly associated with LVH after adjustment for relevant clinical variables (IR: P = 0.012; SBP: P = 0.025). Patients with the AA genotype of the rs9838915 KLF15 variant were more likely to have LVH (OR 1.19; 95% CI 1.05–1.35, P = 0.006). This association was attenuated in used metformin users (OR 1.01; 95% CI 0.96–1.08, P = 0.64, interaction P-value 0.027), suggesting that metformin might also reduce BCAA uptake into tissues. Our analysis of BCAAs in plasma samples from a clinical trial of metformin vs. placebo confirmed this. Finally, in a randomized-controlled clinical trial, metformin reduced indexed LV mass compared to placebo (−3.1 ± 1.9 g/m1.7 vs. −1.2 ± 2.7 g/m1.7; P = 0.005) and SBP (P < 0.001).
Conclusions: We have used genomic studies to help underpin a randomized trial showing that metformin significantly reduced LV mass compared to placebo
|Number of pages||6|
|Journal||QJM : an International Journal of Medicine|
|Publication status||Published - 5 Sep 2019|
|Event||113th Annual Meeting of the Association of Physicians of Great Britian and Ireland - University of Glasgow, Glasgow, United Kingdom|
Duration: 28 Mar 2019 → 29 Mar 2019