Background and Aims: Treatment with metformin (MET) in diabetic patients with chronic heart failure (HF) is associated with better cardiovascular outcomes. The endothelial dysfunction, atherosclerosis and macrovascular diabetic complications are associated with excessive generation of reactive dicarbonyls like methylglyoxal (MG). MET has been proposed as a scavenger of methylglyoxal. The aim of the study was to evaluate the effects of MET on substrate metabolism and dicarbonyl stress in patients with DM and HF.
Materials and Methods: A randomized, double-blind, placebo-controlled, crossover study in a total time of six months testing the effect of 3- month usage of MET (2 g/day) vs. placebo. A group of 40 treatment naive patients with type 2 DM and HF were included. At the beginning and at the end of each intervention period various metabolic tests were done including hyperinsulinemic-isoglycemic clamp, parameters of dicarbonyl stress like MG, Glutathione (GSH), glutathione disulfide (GSSG), and the activity of Glyoxalase1 (GLO-1).
Results: MET significantly reduced HbA1c compared to placebo (p˂0.01). Insulin sensitivity, measured as a metabolic clearance rate of glucose (MCR) during the clamp, improved significantly with MET (p˂0.001) but also, although less significantly, with placebo (p˂0.05), difference between MET and placebo was not significant. Compared to placebo, GHS levels increased after the intervention (baseline vs. MET vs. PL: 866 ± 231 vs. 994 ± 342 vs. 878 ± 266µmol/l, p<0.05). GSH/GSSG ratio was not affected. The levels of MG decreased after MET (p<0.05), decrease after placebo was not significant. The activity of GLO-1 was not affected.
Conclusions: Our results on a unique group of patients with heart failure and diabetes support the evidence that one of the cardioprotective pathways of metformin is through reducing dicarbonyl stress. As there was no change in the GLO-1 activity, it might be due to binding and deactivation of reactive dicarbonyls by MET.
J. Kopecky: None. E. Hošková: None. J. Veleba: None. H. Malinska: None. K. Velebova: None. V. Melenovsky: None. T. Pelikanova: None.
Agentura pro zdravotnický výzkum Ceské Republiky (AZV16-27496A)