Evaluation of mitochondrial functional parameters of peripheral blood mononuclear cells in patients with chronic heart failure and type 2 diabetes mellitus

Abstract

BACKGROUND: The hypothesis that mitochondrial dysfunction may accompany development of chronic heart failure (CHF), type 2 diabetes mellitus (T2DM), and their comorbid forms is supported by real-world clinical observations. In patients with CHF with preserved ejection fraction (CHF-pEF) and reduced ejection fraction (CHF-rEF), as well as in patients with T2DM, mitochondrial stress test to assess mitochondrial respiration of peripheral blood mononuclear cells shows a significant decrease in oxygen consumption by mitochondria of peripheral blood mononuclear cells.

AIM: The aim of the study was to evaluate an informative value of the mitochondrial stress test in patients with CHF with T2DM.

MATERIALS AND METHODS: A total of 23 patients (mean age 69.8±10.1 years) with CHF-pEF and CHF-rEF were included. Patients were divided into groups according to the presence or absence of concomitant T2DM. A mitochondrial stress test was performed using the Seahorse XFe96 analyzer (Agilent Technologies, USA). Mitochondrial respiratory function was assessed in adherent mononuclear cells by simultaneous measurement of oxygen consumption and extracellular proton current flow.

RESULTS: In patients with T2DM, the basal respiratory capacity was reduced 1.5-fold and the reserve respiratory capacity was reduced 3.5-fold compared to the control group. The most inhibitory effect of T2DM on mitochondrial respiration was observed in the CHF-rEF group: 2.1 to 3.0 times lower compared to the control group. Concomitant T2DM was associated with a lower reserve respiration capacity which was also 2.4–4.5 times lower in patients with CHF alone and 18.0 times lower in patients with T2DM alone. In addition, T2DM patients showed a 1.28-fold suppression of non-mitochondrial respiration compared to the control group.

CONCLUSION: Significant mitochondrial dysfunction detected in comorbid patients is associated with the rapid clinical progression of CHF with T2DM and high incidence of decompensation. A decrease in basal and reserve respiratory capacity is a key factor in development of CHF in patients with T2DM.

Keywords

heart failure / mitochondrial stress test / mitochondrial dysfunction / type 2 diabetes mellitus

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