Introduction: Patients with type 2 diabetes (DM) are known to have decreased metabolic flexibility when switching between carbohydrate and lipid oxidation. Our aim was to assess the energy substrates utilization in patients with isolated heart failure (HF) and HF with DM. Methods: A cross-sectional comparative trial with 77 subjects in 4 age matched groups. 21 healthy subjects (HF-DM-), 14 patients with HF alone (HF+DM-), 21 patients with diabetes alone (HF-DM+) and 21 patients with DM or prediabetes and heart failure (HF+DM+). The subjects underwent indirect calorimetry before and during hyperinsulinemic isoglycemic clamp. Results: Metabolic clearance of glucose (MCG) was significantly lower (p ˂ 0.05) in the groups of patients with DM+ (HF-DM-: 6.08 ± 2.03; HF+DM-: 5.86 ± 2.37; HF-DM+: 4.29 ± 2.2; HF+DM+: 3.9 ± 1.76 ml/kg.min). Compared to healthy subjects all the other groups had significantly smaller increase in respiratory quotient during clamp (p ˂ 0.01 for HF-DM- vs. HF+DM- and HF-DM- vs. HF-DM+; p ˂ 0.05 for HF-DM- vs. HF+DM+). Differences between groups with isolated HF and isolated DM were not significant, see Table. Conclusions: Our results on a unique group of patients show similarly deteriorated metabolic flexibility of carbohydrate versus lipid oxidation in patients with type 2 diabetes and heart failure supporting the comparable deleterious effect of both diseases on utilization of energy substrates. Disclosure E. Hošková: None. J. Kopecky: None. J. Veleba: None. K. Velebova: None. V. Melenovsky: None. T. Pelikanova: None. Funding Czech Health Research Council (AZV16-27496A)
Background and Aims: Metformin (MET) treatment in patients with type 2 diabetes (T2D) and chronic heart failure (HF) is associated with better cardiovascular outcomes. Possible mechanism of cardioprotective effect of metformin may be a reduction of dicarbonyl and oxidative stress. In particular, a reduction of methylglyoxal levels (MG). The aim of our study was to evaluate the effect of MET on cardiac structure, cardiac function and exercise capacity in patients with T2D 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 44 treatment naive patients with T2D and HF were included. At the beginning and at the end of each intervention period various metabolic tests were done including echocardiography, spiroergometry, and parameters of dicarbonyl stress like MG, Glutathione (GSH), glutathione disulfide (GSSG), and the activity of Glyoxalase1 (GLO-1). Results: MET treatment led to a decrease in HbA1c levels (∆ MET vs. placebo: -3.39 ± 5.33mmol/mol, p = 0.00007), and fasting plasma glucose levels (∆MET vs. placebo: -0.381 ± 1.1mmol/l; p = 0.00145). MET had no effect on oxygen consumption at the maximum tolerated load during spiroergometry (VOmax) (∆MET vs. placebo: -0.142 ± 1.18ml/kg/min; p = 0.64). MET did not affect left ventricular ejection fraction (∆MET vs. placebo: -0.789 ± 6.32%; p = 0.53). The levels of MG didn’t change after MET (∆ MET vs. placebo: 0.0306 ± 0.13nmol/ml; p = 0.19). The activity of GLO-1 was not affected too (∆ MET vs. placebo: 0.0073 ± 0.017 mmol/min/mg Hb; p = 0.22). Conclusion: MET treatment is safe in patients with severe heart failure. Our results do not support the evidence that one of the cardioprotective pathways of metformin is through reducing dicarbonyl stress. Disclosure E. Hošková: None. J. Kopecky: None. J. Veleba: None. H. Malinska: None. K. Velebova: None. V. Melenovsky: None. T. Pelikanova: None. Funding Institute for Clinical and Experimental Medicine 00023001)
Introduction: Metformin (MET) is a 1st choice drug used in patients with type 2 diabetes (DM). Treatment with MET in patient with DM and heart failure (HF) is associated with better cardiovascular outcomes, but mechanisms of MET-mediated effects are unexplained. Our aim was to evaluate the effects of MET on substrate metabolism, cardiac function and structure in patient with DM and HF. Methods: 40 patients with DM and stable chronic HF (age: 59 ± 9 years) were studied in a random sequence cross-over clinical study testing the effect of 3-month usage of MET vs. placebo. The subjects were randomized to MET (2 g/day) or to placebo group. After the three months of treatment the medication was changed and the treatment continued for next 3 months. At the beginning and the end of each intervention period (3 times in total) the panel of various metabolic and cardiovascular tests was done: echocardiography, spiroergometry and meal test with evaluation of several variables like incretins (GLP-1 and peptide YY) and parameters of oxidative stress (MCP-1, TNFα). Results: Compared to placebo, MET was accompanied with significantly higher increase of selected gut-related hormones. GLP-1 area-under-curve increased during the meal test (MET vs. PL: 8571.39±6899.57 vs. 5665.82±4580.57pmol.hour.l-1; p<0.01). Also the peptide YY area-under-curve increased during the meal test (MET vs. PL: 29809.67±13442.43 vs. 23636.21±8183.08pmol.hour.l-1; p<0.05). MCP-1 showed inconsistent trend to increase during meal test. Fasted levels of TNFα were higher after MET, but there was no change during the meal test compared to placebo. MET therapy led to reduction of HbA1C (p<0.001) and reduced glucose area-under-curve (p<0.001) during glucose tolerance test. MET had neutral effect on cardiac structure and function. Conclusions: Our results suggest that metabolic effects of MET might be mediated by improvement of gut endocrine function. MET had neutral effect on cardiac function or structure. Disclosure E. Stolarikova: None. J. Kopecky: None. J. Veleba: None. K. Velebova: None. L. Belinova: None. V. Melenovsky: None. J. Kopecky: None. T. Pelikanova: None.
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