Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>p</a:mi> <a:mo><</a:mo> <a:mn>0.05</a:mn> </a:math> ). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>p</c:mi> <c:mo>=</c:mo> <c:mn>0.01</c:mn> </c:math> and <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>p</e:mi> <e:mo>=</e:mo> <e:mn>0.03</e:mn> </e:math> , respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>p</g:mi> <g:mo>=</g:mo> <g:mn>0.043</g:mn> </g:math> and <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>p</i:mi> <i:mo>=</i:mo> <i:mn>0.033</i:mn> </i:math> , respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area ( <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>r</k:mi> <k:mo>=</k:mo> <k:mo>−</k:mo> <k:mn>0.58</k:mn> </k:math> , <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>p</m:mi> <m:mo>=</m:mo> <m:mn>0.001</m:mn> </m:math> ), PIIINP, TIMP-1, and LV end-diastolic volume ( <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>r</o:mi> <o:mo>=</o:mo> <o:mo>−</o:mo> <o:mn>0.68</o:mn> </o:math> and <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>p</q:mi> <q:mo>=</q:mo> <q:mn>0.042</q:mn> </q:math> and <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>r</s:mi> <s:mo>=</s:mo> <s:mn>0.38</s:mn> </s:math> and <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>p</u:mi> <u:mo>=</u:mo> <u:mn>0.02</u:mn> </u:math> , respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.