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 p < 0.05 ). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF ( p = 0.01 and p = 0.03 , respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF ( p = 0.043 and p = 0.033 , respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area ( r = − 0.58 , p = 0.001 ), PIIINP, TIMP-1, and LV end-diastolic volume ( r = − 0.68 and p = 0.042 and r = 0.38 and p = 0.02 , 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.

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Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-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) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05 ). Gal − 3 > 10  ng/ml ( OR = 2.25 ; 95% CI, 1.88–5.66; p = 0.01 ) and NT − pro − BNP > 80  pg/ml ( OR = 2.64 ; 95% CI, 1.56–4.44; p = 0.001 ) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.