Adropin is a multifunctional secreted protein, which is involved in the metabolic modulation of the heart-brain-kidney axis in heart failure (HF). The aim of the study was to detect the plausible predictive value of serum levels of adropin for chronic kidney disease (CKD) grades 1–3 in type 2 diabetes mellitus (T2DM) patients with chronic HF. We enrolled 417 T2DM individuals with chronic HF and subdivided them into two groups depending on the presence of CKD. The control group was composed of 25 healthy individuals and 30 T2DM patients without HF and CKD. All eligible patients underwent an ultrasound examination. Adropin was detected by ELISA in blood samples at the study baseline. We found that adropin levels in T2DM patients without HF and CKD were significantly lower than in healthy volunteers, but they were higher than in T2DM patients with known HF. The optimal cut-off point for adropin levels was 2.3 ng/mL (area under the curve [AUC] = 0.86; 95% CI = 0.78–0.95; sensitivity = 81.3%, specificity = 77.4%). The multivariate logistic regression adjusted for albuminuria/proteinuria showed that serum levels of adropin <2.30 ng/mL (OR = 1.55; p = 0.001) independently predicted CKD. Conclusions: Low levels of adropin in T2DM patients with chronic CH seem to be an independent predictor of CKD at stages 1–3.

Background: adropin plays a protective role in cardiac remodeling through supporting energy metabolism and water homeostasis and suppressing inflammation. Low circulating levels of adropin were positively associated with the risk of cardiovascular diseases and type 2 diabetes mellitus (T2DM). We hypothesized that sodium–glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin might represent cardiac protective effects in T2DM patients with known chronic HF through the modulation of adropin levels. Methods: we prospectively enrolled 417 patients with T2DM and HF from an entire cohort of 612 T2DM patients. All eligible patients were treated with the recommended guided HF therapy according to their HF phenotypes, including SGLT2 inhibitor dapagliflozin 10 mg, daily, orally. Anthropometry, clinical data, echocardiography/Doppler examinations, and measurements of biomarkers were performed at the baseline and over a 6-month interval of SGLT2 inhibitor administration. Results: in the entire group, dapagliflozin led to an increase in adropin levels by up to 26.6% over 6 months. In the female subgroup, the relative growth (Δ%) of adropin concentrations was sufficiently higher (Δ% = 35.6%) than that in the male subgroup (Δ% = 22.7%). A multivariate linear regression analysis of the entire group showed that the relative changes (Δ) in the left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e` were significantly associated with increased adropin levels. In the female subgroup, but not in the male subgroup, ΔLVEF (p = 0.046), ΔLAVI (p = 0.001), and ΔE/e` (p = 0.001) were independent predictive values for adropin changes. Conclusion: the levels of adropin seem to be a predictor for the favorable modification of hemodynamic performances during SGLT2 inhibition, independent ofN-terminal brain natriuretic pro-peptide levels.

Cell-free nuclear (cf-nDNA) and mitochondrial (cf-mDNA) DNA are released from damaged cells in type 2 diabetes mellitus (T2DM) patients, contributing to adverse cardiac remodeling, vascular dysfunction, and inflammation. The purpose of this study was to correlate the presence and type of cf-DNAs with HF in T2DM patients. A total of 612 T2DM patients were prescreened by using a local database, and 240 patients (120 non-HF and 120 HF individuals) were ultimately selected. The collection of medical information, including both echocardiography and Doppler imagery, as well as the assessment of biochemistry parameters and the circulating biomarkers, were performed at baseline. The N-terminal brain natriuretic pro-peptide (NT-proBNP) and cf-nDNA/cf-mtDNA levels were measured via an ELISA kit and real-time quantitative PCR tests, respectively. We found that HF patients possessed significantly higher levels of cf-nDNA (9.9 ± 2.5 μmol/L vs. 5.4 ± 2.7 μmol/L; p = 0.04) and lower cf-mtDNA (15.7 ± 3.3 μmol/L vs. 30.4 ± 4.8 μmol/L; p = 0.001) than those without HF. The multivariate log regression showed that the discriminative potency of cf-nDNA >7.6 μmol/L (OR = 1.07; 95% CI = 1.03–1.12; p = 0.01) was higher that the NT-proBNP (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.04–1.19; p = 0.001) for HF. In conclusion, we independently established that elevated levels of cf-nDNA, originating from NT-proBNP, were associated with HF in T2DM patients.

Type 2 diabetes mellitus (T2DM) remains a powerful predictor of progressive heart failure (HF), but it is not clear whether altered glycemic control interferes with HF progression via an impaired profile of circulating myokines. The aim was to investigate plausible effects of glucose control on a myokine signature in T2DM patients affected by chronic HF. We selected 372 T2DM patients from the local database and finally included 314 individuals suffering from chronic HF and subdivided them into two groups according to glycosylated hemoglobin (HbA1c) levels (<6.9% and ≥7.0%). Echocardiography and Doppler examinations along with biomarker measurements were performed at the baseline of the study. The results showed that irisin levels were significantly lower in patients with HbA1c ≥ 7.0% than in those with HbAc1 < 6.9%, whereas concentrations of apelin, myostatin and adropin did not significantly differ between these two groups. We also identified numerous predictors of poor glycemic control, but only N-terminal brain natriuretic propeptide (odds ratio [OR] = 1.07; 95% confidence interval [CI] = 1.02–1.10, p = 0.04) and irisin (OR = 1.09; 95% CI = 1.04–1.17, p = 0.001) remained independent predictors of the dependent variable. In conclusion, we found that decreased levels of irisin were associated with poor glycemic control in T2DM patients with HF regardless of clinical conditions and other biomarkers.

Background: hyperglycemia is a trigger for structural alteration of red blood cells (RBCs) and their ability to release extracellular vesicles (EVs). The aim of the study was to elucidate whether glucose control in T2DM patients with concomitant HF and AF affects a circulating number of RBC-derived EVs. Methods: we prospectively included 417 T2DM patients with HF, 51 of them had atrial fibrillation and 25 healthy volunteers and 30 T2DM non-HF individuals. Clinical assessment, echocardiography examination and biomarker measures were performed at the baseline of the study. RBC-derived EVs were determined as CD235a+ PS+ particles by flow cytometry. NT-proBNP levels were measured by ELISA. Results: AF patients with glycosylated hemoglobin (HbA1c) < 6.9% had lower levels of CD235a+ PS+ RBC-derived vesicles than those with HbA1c ≥ 7.0%. There were no significant differences in number of CD235a+ PS+ RBC-derived vesicles between patients in entire cohort and in non-AF sub-cohort with HbA1c < 6.9% and HbA1c ≥ 7.0%, respectively. Multivariate linear regression yielded that CD235a+ PS+ RBC-derived vesicles ≥ 545 particles in µL (OR = 1.06; 95% CI = 1.01–1.11, p = 0.044) independently predicted HbA1c ≥ 7.0%. Conclusions: elevated levels of CD235a+ PS+ RBC-derived EVs independently predicted poor glycaemia control in T2DM patients with HF and AF.