Marcin Kosmalski

Background: Type 2 diabetes mellitus (T2DM) is associated with disturbances in mineral element homeostasis, yet data on calcium (Ca), magnesium (Mg) and iron (Fe) across multiple blood compartments in T2DM throughout the spectrum of renal function remain limited. Objective: To assess Ca, Mg and Fe concentrations in plasma, whole blood and erythrocytes of T2DM patients with reduced or preserved estimated glomerular filtration rate (eGFR), integrating three-day dietary records to explore, rather than definitively separate, metabolic and dietary drivers of imbalance. Methods: In this single-center, cross-sectional study, 91 hospitalized adults were divided into three groups: controls (n = 32), T2DM with preserved eGFR (≥60 mL/min/1.73 m²; n = 29), and T2DM with reduced eGFR (2; n = 30). Renal function was assessed using eGFR calculated with the Modification of Diet in Renal Disease (MDRD) equation. The eGFR-based grouping did not constitute a diagnosis or staging of chronic kidney disease. Mg, Ca, and Fe concentrations were measured in plasma and whole blood using atomic absorption spectrometry. Plasma Ca concentrations were corrected for albumin, whereas blood cell Fe and Mg concentrations were calculated using individual hematocrit values. Blood cell Ca could not be quantified. Dietary intake was assessed from three-day food diaries completed during hospitalization (hospital diet). Between-group differences in mineral concentrations were assessed using Welch’s ANOVA followed by Games–Howell post hoc comparisons. Associations between calculated blood cell Fe concentrations and hematological indices were evaluated using Spearman’s rank correlation coefficient, with Benjamini–Hochberg correction for multiple comparisons. Results: Plasma Mg (p < 0.01) and albumin-corrected plasma Ca (p < 0.05) were lower in the T2DM group with eGFR < 60 mL/min/1.73 m² than in controls; albumin-corrected plasma Ca was also lower in this group than in the T2DM group with eGFR ≥ 60 mL/min/1.73 m² (p < 0.01); whole-blood Mg was higher in the T2DM group with eGFR ≥ 60 mL/min/1.73 m² than in controls (p < 0.05). Whole-blood Fe was significantly higher in both T2DM groups than in controls (p < 0.05), whereas calculated blood cell Fe did not differ significantly between groups after hematocrit-based recalculation. Blood cell Mg did not differ significantly between groups. Dietary Ca intake was lower (p < 0.01) and Mg intake higher (p < 0.01) in T2DM than in controls. Conclusions: Mineral concentration differences in T2DM varied across blood compartments. Although whole-blood Fe was elevated in both T2DM groups, no significant differences were detected in hematocrit-adjusted blood cell Fe concentrations. These findings do not establish intracellular Fe accumulation or hepcidin-mediated sequestration. Further studies incorporating direct intracellular measurements, comprehensive Fe-status markers, and adjustment for clinical confounders are needed to determine the potential diagnostic value of mineral measurements beyond plasma.

Background: Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Glutathione reductase (GR) and microRNA-144 (miR-144) may participate in redox-related pathways. This study aimed to evaluate relative GSR mRNA and miR-144 expression in peripheral blood samples from patients with and without AF and to explore their associations with selected clinical characteristics. Methods: This case–control study included 189 hospitalized adults: 95 without AF and 94 with AF. Clinical, anthropometric, biochemical, and echocardiographic data were collected for all participants. GSR mRNA was assessed by quantitative real-time PCR in whole blood samples, whereas circulating miR-144 expression was evaluated in serum. Group differences were assessed using nonparametric tests, correlations were evaluated using Spearman’s rank correlation coefficient, and multivariable logistic regression was used to identify variables independently associated with AF. Model stability was assessed using bootstrap internal validation. Results: Relative GSR mRNA expression was significantly lower in the AF group than in controls (0.1539 vs. 0.2058, p < 0.001), whereas miR-144 expression was significantly higher in patients with AF (0.3636 vs. 0.2550, p = 0.0183). In multivariable logistic regression adjusted for clinical confounders, higher miR-144 (OR = 1.336, p = 0.048) and lower GSR (OR = 0.343, p < 0.001) expression remained associated with AF. Bootstrap internal validation supported the statistical stability of the GSR association (optimism-corrected AUC = 0.709, bootstrapped 95% CI: 0.622–0.785), whereas miR-144 showed only a more modest and less stable association (optimism-corrected AUC = 0.598, bootstrapped 95% CI: 0.519–0.684); both signals remain exploratory and do not yet support routine clinical use as diagnostic or risk-stratification biomarkers in AF. Both markers showed exploratory correlations with selected clinical and biochemical variables. Given the cross-sectional design of the study, all reported relationships should be interpreted as statistical associations rather than as evidence of causality. The observed correlations between molecular markers and clinical parameters are hypothesis-generating and warrant further investigation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial metabolic disorder that is strongly associated with mitochondrial dysfunction and oxidative stress, which may potentially compromise the integrity of mitochondrial DNA (mtDNA). However, the role of the base excision repair (BER) pathway—the main mechanism responsible for repairing oxidative lesions in mitochondria—and maintaining mtDNA stability in MASLD remains poorly understood. Here, we analyzed total mRNA expression levels of key BER components in whole-blood samples, along with mitochondrial protein levels of the selected components. Additionally, we assessed the mtDNA copy number and the damage of mtDNA and nuclear DNA in peripheral leukocytes from MASLD patients and healthy controls. We found that MASLD patients differed from controls in mtDNA and nuclear DNA damage, mtDNA copy number, and selected BER-related markers. However, because the MASLD and control groups also differed substantially in age and BMI, these molecular differences should be interpreted as potentially being associated with age- and BMI-related metabolic status rather than attributable to MASLD alone. While several BER-related genes were downregulated at the mRNA level, the corresponding mitochondrial protein levels were not consistently decreased in MASLD (ProteomeXchange: PXD075974), indicating a discordance between transcriptional and protein-level regulation. These results suggest that altered mitochondrial BER and mtDNA instability in peripheral leukocytes may reflect the combined influence of MASLD, aging, obesity, and broader metabolic dysfunction.

The last decade has transformed the conceptual landscape of fatty liver disease in three ways

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to atrial fibrillation (AF); however, its relationship with specific AF subtypes remains unclear. This prospective, single-center, observational case–control study investigated whether MASLD is independently associated with AF presence and its subtypes. Materials: A total of 327 participants were analyzed, including 119 controls and 208 patients with AF. Comprehensive clinical history, anthropometric measures, laboratory testing, 24 h Holter ECG, and echocardiography were performed. Clinically inferred MASLD was defined according to the current EASL–EASD–EASO guidelines using clinical and non-invasive indices (Hepatic Steatosis Index, Fatty Liver Index, Fibrosis-4 Index). No liver biopsy or imaging confirmation of steatosis or fibrosis was performed, and therefore, the diagnosis represents a clinically inferred (“probable”) MASLD. To minimize systematic bias and improve baseline comparability between groups, propensity score matching and complementary regression analyses were applied. Results: Overall probable MASLD prevalence did not differ between AF and controls (42% vs. 44%, p = 0.742). A clear phenotypic gradient emerged across subtypes: lowest in permanent AF (PermAF, 27.1%) versus paroxysmal (47.1%) and persistent AF (51.4%) (p = 0.021). PermAF exhibited the most advanced comorbidity—highest CHF (78.6%), CKD (71.4%), HFpEF (48.6%), FIB-4 (median 2.67), the lowest TG/HDL–cholesterol ratio (1.93 vs. 3.32; p < 0.001), and progressive renal impairment. Statin therapy reached 80% in clinically inferred MASLD-positive PermAF. The elevated FIB-4 observed in PermAF must be interpreted with explicit caution: this group was substantially older (median 79.5 years) and carried the highest burden of chronic heart failure and chronic kidney disease; therefore, in this subgroup, FIB-4 most plausibly reflects age and cardio-renal comorbidity rather than histologically confirmed hepatic fibrosis. After matching, MASLD was not an independent predictor of AF presence (OR = 0.96; 95% CI: 0.59–1.46) or its clinical severity. Conclusions: Probable MASLD, defined by clinical and non-invasive indices, was not independently associated with AF in this cohort, but AF subtypes exhibited a clear phenotypic gradient—from a metabolically driven profile in early AF to a cardio-renal and fibrotic pattern in advanced, elderly AF. Elevated FIB-4 values in PermAF most plausibly reflect age and cardio-renal comorbidity rather than true histologically confirmed hepatic fibrosis. These findings support a phenotype- and population-dependent MASLD–AF relationship and underscore the need for imaging- and histology-verified longitudinal studies.

P53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation—processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating TP53 and SIRT-1 serum miR-34a expression were determined in patients with and without AF, in order to assess their associations with AF. We also checked their potential diagnostic utility as systemic biomarkers associated with AF. The study included 189 adults, 94 AF+, 95 AF−. Clinical, anthropometric, and biochemical data were collected. Whole-blood TP53 and SIRT-1 mRNA expression and serum miR-34a expression were quantified by RT-qPCR. ROC analysis and Youden-derived odds ratios assessed exploratory diagnostic performance. AF patients had significantly higher expression of TP53 (0.0352 vs. 0.0253; p < 0.001) and miR-34a (0.0215 vs. 0.0099; p < 0.001), but significantly lower expression of SIRT-1 (0.0079 vs. 0.0145; p < 0.001). The level of SIRT-1 expression showed the highest discriminatory performance (exploratory AUC = 0.6987; p < 0.0001). TP53 expression levels exceeding 0.0295 were associated with nearly threefold higher odds of AF (OR = 2.92, 95% CI: 1.61–5.28, p = 0.0006), whereas the expression levels of SIRT-1 and miR-34a were not significantly associated with AF in cut-off analysis. In the AF group, a positive correlation was found between the expression of TP53 and SIRT-1 (Rho = 0.3609, p < 0.001); however, it was not consistent with a canonical model of miR-34a-mediated SIRT-1 suppression. In turn, the expression of miR-34a correlated positively with age and C-reactive protein level and negatively with estimated glomerular filtration rate (eGFR). The obtained results suggest that AF is associated with altered expression of circulating TP53, SIRT-1, and miR-34a. However, due to the fact that the expression levels were measured in peripheral compartments, and not in atrial tissue, the obtained results should not be interpreted as direct evidence of AF-related atrial remodeling. For these reasons, further investigations involving simultaneous measurements of the TP53/miR-34a/SIRT-1 regulatory axis, both in the circulating compartment and atrial tissue, should be performed.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders and has been linked to oxidative stress. Therefore, it can be hypothesized that NAFLD may be associated with genes encoding proteins involved in the base-excision repair (BER) pathway. Moreover, mitochondrial dysfunction plays a significant role in the development of NAFLD. In light of these observations, we suggested that fatty liver may be associated with genes that encode proteins responsible for mitochondrial DNA (mtDNA) degradation. This study evaluates single-nucleotide polymorphisms (SNPs) within the EXOG, ENDOG, POLG, FEN1, PARP1, and XRCC1 genes in 99 patients and 104 controls. SNP genotyping was performed using TaqMan probes and the findings were presented as odds ratios with corresponding 95% confidence intervals. Each of the eight investigated SNPs was found to modulate the risk of NAFLD occurrence. The analysis revealed that the studied haplotypes of EXOG and XRCC1 significantly affected the frequency of NAFLD in patients. The findings allow us to assume that there is a link between FEN1, PARP1, XRCC1, POLG, EXOG, and ENDOG and liver steatosis. We believe that the impaired repair and degradation of damaged mtDNA may have a significant impact on the development of NAFLD.

Background: There are ongoing attempts to find a reliable, highly sensitive and specific early indicator of myocardial ischemia. Recently, a potential new function for the “non-pregnancy”-related pregnancy-associated plasma protein-A (PAPP-A) protein has been reported in many papers, including that the protein could be used in diagnosing heart conditions. Hence, our study aimed to determine the diagnostic and prognostic significance of PAPP-A protein in individuals diagnosed with non-ST-elevation acute coronary syndromes (NSTE-ACSs). Methods: The study comprised 100 consecutive patients (68 males and 32 females), aged from 42 to 83 years (mean age: 64.2 years). We assessed PAPP-A protein levels, anthropometric measurements, basic laboratory tests, ECG recordings, and coronary angiography for each patient. The participants were subsequently divided into two groups: non-ST-elevation myocardial infarction (NSTEMI, n = 74) or unstable angina (UA, n = 25). Results: The levels of PAPP-A protein in patients with NSTEMI were slightly higher than those in patients with UA, but the difference was not statistically significant (7.93 ± 6.35 mIU/L vs. 6.52 ± 5.45 mIU/L, p = 0.253). Higher PAPP-A protein levels (≥5.83 mIU/L) were associated with a numerically higher, but not statistically significant, risk of NSTEMI (OR = 1.37; 95% CI: 0.56–3.36). After 12 months, there was a significant correlation between the amount of labelled PAPP-A protein and the likelihood of experiencing acute myocardial infarction, cardiovascular death, and the necessity for unplanned coronary angiography. Conclusions: The diagnostic utility of PAPP-A protein in NSTE-ACS is limited, both in the NSTEMI and UA patient groups. However, its measurement can be used to estimate the annual risk for these groups of patients.

Background/Objectives: The aim of the study was to analyze dietary and lifestyle adherence in patients with type 2 diabetes mellitus (T2DM) under the care of a diabetes clinic. Methods: The study included two groups: patients under the close control of a dietitian (n = 50) who followed a standard (DD) or fiber-enriched diabetic diet (FD), and patients under the care of a diabetes clinic without close supervision of a dietitian (n = 50). Results: After 3 months, both DD and FD significantly improved metabolic control in the patients under the care of a dietitian. However, FD was slightly better compared to DD (BMI reduction by an average of 2.4% (95% CI: 1.6%; 3.1%) for DD vs. 4.8% (95% CI: 3.6%; 6.0%) for FD; waist circumference decreasing 2.0% (95% CI: 1.2%; 3.4%) for DD vs. 3.5% (95% CI: 2.6%; 4.3%) for FD, p < 0.01; glycemia reduction 19.9% (95% CI: 14.8%; 25.0%) for FD vs. 5.6% (95% CI: 1.9%; 9.3%) for DD, p < 0.001; GGTP activity reduction 35.7% (95% CI: 28.9%; 42.5%) for FD vs. 1.8% (95% CI: −15.2%; 18.3%) for DD, p < 0.001). In addition, only half of the patients without the close supervision of a dietitian declared adherence to the diet. Most respondents had a satisfactory level of nutritional knowledge, but the analysis indicates the weakly marked influence of the protective features of nutrition as well as evidence of the low contribution of an unhealthy diet. Conclusions: Considering the level of nutritional knowledge and low awareness of their health condition in many patients, visits to the doctor and brief nutrition education are not enough for dietary care in T2DM patients. A dietitian’s care is necessary to improve their health.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and atrial fibrillation (AF) are two highly prevalent conditions that share overlapping cardiometabolic risk factors, including obesity, type 2 diabetes, hypertension, and dyslipidemia. Growing evidence suggests that these two disease entities are pathophysiologically linked through systemic inflammation, oxidative stress, and structural remodeling. Population-based studies and meta-analyses report an association between steatotic liver disease and both incident and recurrent AF. While several analyses observe persistence of this association after adjustment for cardiometabolic risk factors, residual confounding and limitations of observational designs preclude firm causal inference. Conversely, heart rhythm disturbances may exacerbate hepatic fibrosis and dysfunction. Lifestyle interventions—particularly sustained weight loss—have demonstrated significant benefits in both conditions. Emerging pharmacological options, including incretin mimetics, flozins, statins, and thiazolidinediones, show promise in addressing the liver–heart axis, while appropriate anticoagulation remains essential in AF management. This review summarizes current epidemiological data, mechanistic insights, diagnostic approaches, and therapeutic strategies related to the coexistence of MASLD and AF. Emphasis is placed on shared pathogenic pathways, non-invasive diagnostic tools, and integrated management options.