Biomarkers of diabetes: role in the pathogenesis of atrial fibrillation.

The prevalence of both atrial fibrillation (AF) and diabetes is increasing day by day and commonly co-exist with a longer duration of diabetes and poor control, putting the individual at higher risk of AF. This review article presented some traditional and novel biomarkers related to AF in patients with diabetes mellitus. The literature review employed several databases, including Google Scholar, PubMed, and Science Direct. The investigation was finished on October 30, 2023. Many terms are utilized, including "AF", "Biomarkers", "Diabetes Mellitus", and "Pathogenesis". There are numerous biomarkers of diabetes, but this review article reports only leptin, adiponectin, glycated hemoglobin, ceramide, ferritin, fibrinogen, hematological indices, interleukin-18, thrombospondin 1, acylcarnitine, plasminogen activator inhibitor-1 and triglycerides and high-density lipoprotein cholesterol, since those biomarkers play a significant role in the pathogenesis of AF. However, no data was found, including fructosamine, glycated albumin, 1,5 anhydroglucitol, fetuin-A, α-hydroxybutyrate, mannose-binding lectin serine peptidase, transferrin, IL-1 receptor antagonist in AF. Understanding the interplay between diabetes and AF through the measurement of relevant biomarkers can contribute to better risk assessment, early detection, and the development of targeted therapeutic strategies for individuals at risk or already affected by these conditions.

Novel anthropometric parameters in the adult population with prediabetes.

OBJECTIVE: Although it is assumed that novel-derived anthropometric indices can better reflect cardiometabolic risk than traditional ones, the results are conflicting. Previous studies have mainly focused on patients with type 2 diabetes mellitus. However, studies conducted on populations with prediabetes are scarce. The present study aimed to examine the potential relationship between prediabetes and novel anthropometric parameters [that is, cardiometabolic index (CMI), visceral adiposity index (VAI), lipid accumulation product index (LAP), body roundness index (BRI), and body adiposity index (BAI)] and traditional parameters [that is, waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR)] in adults with prediabetes. PATIENTS AND METHODS: This case-control cross-sectional study included 177 patients with prediabetes and 609 control subjects. Biochemical and simple anthropometric parameters were measured (WC, HC, body weight, and height), whereas the other parameters were calculated. RESULTS: WC, CMI, VAI, and LAP independently correlated with prediabetes. Principal component analysis (PCA) was used to extract several factors that correlated with prediabetes. Significant predictive capability was demonstrated for non-traditional anthropometric/lipid-related factors and WHipR-related factors for prediabetes (OR=1.334 and OR=1.202, respectively). However, only non-traditional anthropometric/lipid-related factors (i.e., VAI, CMI, and LAP) demonstrated an independent significant positive relationship with prediabetes in multivariate binary regression analysis. CONCLUSIONS: CMI, VAI, and LAP could be superior to BAI, BRI, and conventional anthropometric parameters for discriminating patients with prediabetes in the adult population. Prospective trials are needed to confirm our results.

Red cell distribution width is inversely associated with body mass index in late adolescents.

OBJECTIVE: There are no studies that investigated the association between red blood cell (RBC) and platelet (PLT) indices in relation to obesity in a cohort of exclusively late adolescents. Hence, we aimed to explore this potential relationship. PATIENTS AND METHODS: A cohort of adolescents (n=156) aged between 16-19 years was included. Iron homeostasis parameters [i.e. RBC, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] and platelet indices [i.e., PLT, mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW)] were determined on the automatic hematology analyzer. Their indexes (i.e. MCV/RBC, MCH/RBC, RDW/MCV, MPV/PLT and PDW/PCT) were calculated. RESULTS: Univariate binary regression analysis showed negative associations between body mass index (BMI) and RDW, PDW, and PDW/PCT, respectively, and positive associations between BMI and MPV and PCT, respectively. However, only RDW kept the independent negative association with BMI in multivariate binary regression analysis [Odds Ratio (95% Confidence Interval)=0.734 (0.548-0.983); p=0.038]. CONCLUSIONS: Lower RDW values are the independent predictor of higher BMI in the adolescent population. As a low-cost and simply measured parameter, RDW could be a useful diagnostic biomarker in young populations with overweight/obesity.

Novel leukocyte and thrombocyte indexes in patients with prediabetes and type 2 diabetes mellitus.

OBJECTIVE: To our knowledge, there are no studies that investigated the relationship between diabetes mellitus type 2 (T2D) and some novel indexes, such as monocyte/granulocyte to lymphocyte ratio (M/GLR), derived neutrophil to lymphocyte ratio (dNLR), and platelets to neutrophil ratio (PNR). The aim of this study was to examine the association between these novel indexes and glycated hemoglobin (HbA1c) in patients with prediabetes and T2D. PATIENTS AND METHODS: A total of 827 participants were consecutively recruited. According to the American Diabetes Association (ADA) criteria, participants were divided into control, prediabetes, and T2D group. RESULTS: White blood cell count (WBC), neutrophil count, NLR, dNLR, and M/GLR were higher in T2D patients than in the other two groups, whereas PNR was the lowest in T2D group. Lymphocyte count was higher in prediabetes and T2D patients than in control group. Multivariable ordinal regression analysis showed that WBC, neutrophil count, lymphocyte count, NLR, dNLR, and M/GLR were positively associated [OR (95% CI) 1.287 (1.191-1.390), p<0.001; 1.427 (1.275-1.594), p<0.001; 1.347 (1.130- 1.606), p=0.001; 1.350 (1.090-1.670), p=0.006; 1.662 (1.189-2.326), p=0.003; 1.275 (1.057-1.540), p=0.012, respectively] with HbA1c. However, PNR was negatively associated with HbA1c [0.987 (0.981-0.993), p<0.001]. CONCLUSIONS: Novel, modified NLR indexes, such as dNLR and M/GLR were independently correlated with HbA1c. Also, PNR showed superiority over platelets (PLT) in relation to HbA1c. These novel indexes might give a significant contribution to the timely recognition of disturbances of glucose homeostasis in patients with prediabetes and overt diabetes.

Oxidative stress and inflammation parameters-novel biomarkers for idiopathic pulmonary fibrosis.

OBJECTIVE: The pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are not well elucidated. It is assumed that oxidative stress and inflammation are the key underlying culprits for its onset and progression. To gain deeper insight into these processes, we have evaluated several oxidative stress parameters, inflammation markers [i.e., high sensitivity C-reactive protein (hsCRP), serum amyloid A1 (SAA1)], soluble programmed cell death-ligand 1 (sPD-L1), and 25-hydroxyvitamin D [25(OH)D] in IPF patients. PATIENTS AND METHODS: Biochemistry analyses were done in 30 consecutive IPF patients and 30 age and gender-matched healthy control group (CG). RESULTS: IPF patients had significantly higher advanced oxidation protein products (p<0.001), pro-oxidant-antioxidant balance (p=0.010), total oxidative status (p<0.001), and ischemia modified albumin (p<0.001) compared to CG. Lower total antioxidant status and total sulfhydryl groups (tSGH) and significantly higher sPD-L1, hsCRP (p<0.001 for all), SAA1 proteins (p=0.014) and [25(OH)D] severe deficiency [11.0 (9.6-15.1) nmol/L] in IPF patients compared to CG were observed. Paraoxonase 1 activity and hsCRP level were lower, while tSHG and sPD-L1 were higher in IPF patients with more severe disease (i.e., II+III stage compared to I stage, p<0.05 for all). CONCLUSIONS: IPF patients are in a state of profound oxidative stress compared to healthy people. The inflammatory component of the disease was confirmed by higher hsCRP and SAA1, but lower [25(OH)D] in IPF than in healthy people. Also, higher levels of sPD-L1 in patients with IPF compared to healthy individuals suggest that sPD-L1 may have a significant role in immune response in IPF.

A non-invasive method for estimating the severity of liver steatosis and the risk of fibrosis in non-obese type 2 diabetes patients with NAFLD.

Context: Prognostic considerations include assessing the risk of liver fibrosis in people with non-alcoholic fatty liver disease (NAFLD). Objectives: This study evaluates the use of hematologic and metabolic parameters regarding liver steatosis and fibrosis scores (FLI and Fib-4) in non-obese type 2 diabetes mellitus (t2DM) patients with NAFLD. Methods: Subjects underwent abdominal ultrasound examinations, and FLI and Fib-4 scores were calculated to evaluate liver steatosis and the risk of liver fibrosis non-invasively: 61 non-obese NAFLD subjects with t2DM were included in the cohort study and were divided into 2 groups depending on the t2DM treatment regimen. Results: Fib-4 and WBC count demonstrated a significant inverse correlation (OR = 0.509, p = 0.007). WBC count had an R2 of 0.237, indicating that this marker could account for up to 23.7% of a variation in Fib-4. Fib-4 and FFA had positive correlation which did not achieve statistically significant prediction (OR=7.122, p=0.062). Additionally, a significant prediction of HbA1c (OR=1.536, p=0.016) and haemoglobin (OR=1.071, p=0.020) for FLI was revealed. Conclusion: HbA1c and other haematological and metabolic parameters, such as haemoglobin and WBC, may be another non-invasive tool for determining whether non-obese NAFLD patients with t2DM are at risk of developing liver steatosis and fibrosis.

Comparative study of immunohistochemical determination of breast cancer molecular subtypes on core biopsy and surgical specimens.

OBJECTIVE: We aimed to compare the distribution of different molecular subtypes of invasive breast cancer (BC) between patients whose samples were obtained by core needle biopsy (CB) and surgical specimens (SS) and to assess the reliability of CB as a diagnostic method in this context. PATIENTS AND METHODS: All patients (222) diagnosed with invasive BC were examined. Immunohistochemistry was performed on 40 samples obtained by CB and on 148 SS, while in 34 patients, the analysis was performed on both CB and SS. Molecular classification of BC was performed based on estrogen receptor (ER), progesterone receptor (PgR), Human epidermal growth factor receptor 2 (HER2), and Ki67 proliferative index status. RESULTS: The most common molecular subtypes were Luminal A (43.2%) and Luminal B HER2- (29.7%). When comparing the frequencies of determined molecular subtypes, no difference was observed between samples obtained by CB and SS (p>0.05). Concordance analysis of molecular subtypes determined by immunohistochemistry on CB and SS was performed in 34 patients whose samples were obtained using both methods. No significant difference was observed in the designation of molecular subtype in relation to the sampling method (p>0.05). Results of immunohistochemistry analysis on CB and SS demonstrated good statistical agreement (Concordance rate=85.29%, Kappa=0.771, p<0.001). CONCLUSIONS: CB might be a reliable method for the determination of the molecular subtype of invasive BC.

Total leukocyte count, leukocyte subsets and their indexes in relation to cardiovascular risk in adolescent population.

OBJECTIVE: No studies investigated total leukocytes, their subpopulations and novel indexes based on different ratios of leukocyte subsets concerning cardiovascular risk (CV) risk in late adolescents. Therefore, the aim of the present study was to explore such potential relationships. PATIENTS AND METHODS: A total of 156 adolescents were included. CV risk score was calculated by summarizing each risk factor (i.e., female sex, low high density lipoprotein cholesterol (HDL-c), high non-HDL-c, smoking, blood pressure, and fasting glycemia). Adolescents were divided into a low CV risk score (i.e., -2≤ CV risk score ≤1) and moderate/higher CV risk score (i.e., CV risk score ≥ 2). White blood cell count (WBC) and its subsets were analyzed on an automatic device. The indexes were calculated. RESULTS: Total and differential WBC counts except basophil count were higher in moderate/higher CV risk participants. Multivariate binary regression analysis showed that total WBC count independently increased CV risk score by 1.623 times (p=0.001). Neutrophil and eosinophil counts (p=0.027 and p=0.010, respectively) were independently able to increase CV risk score by 1.486 and 1.556 times, respectively. On the contrary, indexes were not independently correlated with CV risk. CONCLUSIONS: WBC, neutrophil, and eosinophil count are the independent predictors of increased CV risk in adolescents. The associations may indicate the different pathways that lead to CV disease in adulthood.

Paraoxonase 1 low activity and SYNTAX score may predict postoperative complications after coronary artery surgery.

OBJECTIVE: Coronary artery bypass grafting (CABG) seems to present a powerful trigger of oxidative stress (OS) and acute inflammatory response. This study aimed to estimate the effects of off-pump coronary artery bypass (OPCAB) grafting on the OS that is commonly observed in patients undergoing operation under cardiopulmonary bypass (CPB). Additionally, we aimed to examine the relationship between and paraoxonase 1 (PON1) activity and the degree of stenosis, severity and complexity of the atherosclerotic lesions, estimated by SYNTAX score (SS). PATIENTS AND METHODS: Study group of 107 patients scheduled for CABG were divided into CPB and OPCAB group. Blood samples for OS markers measurement were collected at six-time intervals: before skin incision (t1), immediately after surgery (t2), 6h (t3), 24h (t4), 48h (t5) and 96h after cessation of the operation and surgical trauma (t6). SS was calculated. RESULTS: A significant decrease in lipid hydroperoxides (LOOH) and advanced oxidation protein products (AOPP) levels after both types of surgeries were observed, whereas PON1 reduction was observed higher in the CPB than in the OPCAB group. A significant inverse correlation between SS values and PON1 activity, preoperatively and during the early postoperative hours after surgery [in t2, t3 time intervals (p<0.05 for all)] was found. ROC analysis showed that for CPB patients, Model with all OS parameters showed excellent accuracy (AUC=0.957, p<0.001) for prediction postoperative complications. CONCLUSIONS: Decrease in PON1 activity during the early post-operative phases was related to higher SS. This relationship was more convincing in CPB, compared with OPCAB patients. Moreover, integrated models of OS status parameters have the capability to predict the development of postoperative complications.

Serum cystatin C levels are associated with triglycerides/high-density lipoprotein cholesterol ratio in adolescent girls ages between 16-19 years old.

OBJECTIVE: The pathophysiological role of cystatin C in cardiometabolic disorders is not completely explored in young population. On the other hand, together with the increase in obesity, dyslipidemia and insulin resistance (IR) are often observed even in youngsters. The aim of the study was to investigate the relationship between cystatin C and triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-c), as an indicator of dyslipidemia and a surrogate marker of IR in the cohort of adolescent girls ages between 16-19 years. PATIENTS AND METHODS: A total of 99 girls were included in the study. Anthropometric and biochemical parameters were provided. Associations of biochemical markers with TG/HDL-c ratio were tested using univariable and multivariable ordinal regression analysis for TG/HDL-c ratio tertiles as dependent variable. RESULTS: In univariate analysis, cystatin C levels were significantly associated with TG/HDL-c ratio (OR=1.813; 95% CI: 1.190-2.757, p=0.005). Furthermore, multivariate analysis revealed that cystatin C was an independent predictor of TG/HDL-c ratio when body mass index and high sensitivity C-reactive protein (i.e., markers that were significantly correlated with TG/HDL-c ratio in Spearman's correlation analysis) were included in the Model. Adjusted odds for cystatin C (OR=1.621; 95% CI: 1.028-2.552, p=0.037) demonstrated that rise in cystatin C by 0.1 mg/L increased the probability for higher TG/HDL-c tertile group by 1.621 times. CONCLUSIONS: Serum cystatin C levels are associated with TG/HDL-c ratio in adolescent girls. Longitudinal studies are needed to confirm the causal relationship between cystatin C and TG/HDL-c ratio and to further explore its diagnostic and therapeutic potential in dyslipidemia and insulin resistance in young population.

Total oxidant status and oxidative stress index as indicators of increased Reynolds risk score in postmenopausal women.

OBJECTIVE: Considering the knowledge gap between underlying pathophysiological mechanisms of oxidative stress and increased cardiovascular risk, the present study aimed to examine the potential relationship between total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) and the Reynolds Risk Score (RRS) in the cohort of postmenopausal women. PATIENTS AND METHODS: A total of 126 postmenopausal women participated in this cross-sectional study. Blood pressure, anthropometric and biochemical markers were determined. OSI was calculated as the TOS/TAS ratio. Associations of biochemical parameters with RRS were tested using univariable and multivariable logistic ordinal regression analysis. RESULTS: TOS and OSI were the highest in women in high RRS category compared to moderate and low risk ones (p<0.001, for both). There was no difference in TAS level across RRS categories (p=0.370). Multivariable ordinal regression analysis showed independent association of TOS and OSI with RRS when tested with other clinical variables [OR=2.45; 95% CI (1.08-5.53); p=0.031 and OR=2.84; 95% CI (1.27-6.36); p=0.011, respectively]. CONCLUSIONS: TOS and OSI are associated with the RRS in the cohort of postmenopausal women. Longitudinal studies are needed to confirm whether adding the TOS and OSI to the standard RRS algorithm could improve its potential to predict cardiovascular event.

Inverse association between serum endocan levels and small LDL and HDL particles in patients with type 2 diabetes mellitus.

OBJECTIVE: Determination of lipoprotein size and subclasses distribution can provide more significant information on cardiovascular disease risk than measurement of traditional lipid parameters alone. Accordingly, we aimed to examine their potential relationship with the novel biomarker of endothelial dysfunction, such as endocan in patients with type 2 diabetes mellitus (T2D), since there are no studies concerning this issue. PATIENTS AND METHODS: This case-control study included a total of 42 individuals with T2D and 64 diabetes-free participants. Serum endocan, lipid parameters, and lipoprotein subclasses were measured. RESULTS: Patients with T2D exhibited higher proportion of the smallest high-density lipoprotein (HDL) particles HDL 3c, as compared with diabetes-free participants (p=0.047). Higher serum endocan levels in T2D patients with low small dense low-density lipoprotein (LDL) particles (sdLDL) %, as compared with corresponding group of diabetes-free subjects was shown (p<0.01). Univariate binary logistic analysis revealed significant positive association of endocan and LDL diameter (OR=1.686, p=0.004), and negative associations of endocan with proportions of sdLDL (OR=0.928, p=0.007) and HDL3b (OR=0.789, p=0.009) particles. In a multivariate analysis, LDL diameter and proportions of sdLDL and HDL3b subclasses remained independent predictors of endocan levels in tested population. CONCLUSIONS: The results of our study showed that larger LDL diameters, but lower sdLDL and HDL3b proportions were associated with higher endocan levels in population with T2D. More studies in the future are needed to confirm the observed relationship and to examine its causal nature.

Endocan and advanced oxidation protein products in adult population with hypertension.

OBJECTIVE: Hypertension is closely related to oxidative stress and inflammation. Endocan is a new inflammation marker whose role is not completely elucidated in hypertension. The aim of this study was to explore the association between endocan and several oxidative stress markers [i.e., advanced oxidation protein products (AOPP), total protein sulfhydryl (SH-) groups and prooxidant-antioxidant balance (PAB)] in adult population with hypertension. PATIENTS AND METHODS: A total of 90 patients with hypertension were compared with 44 controls. Blood pressure, anthropometric and biochemical parameters were measured. Associations of clinical data with hypertension were tested with univariable and multivariable logistic ordinal regression analysis. RESULTS: Endocan and AOPP were significantly higher in hypertensive patients than in the controls (p=0.006 and p=0.046, respectively). In the multivariable logistic regression analysis, AOPP and endocan kept their independent positive associations with hypertension. As AOPP rose by 1 µmol/L and endocan rose by 1 pg/mL, the probability for hypertension presence rose by 4.2% and 32.2%, respectively and 39.9% of variation in hypertension could be explained with the Model. The area under the Receiver Operating Characteristic curve [(AUC) for AOPP=0.638 (0.550-0.719), p=0.01 and for endocan=0.679 (0.593-0.757), p<0.001] demonstrated sufficient clinical accuracy towards hypertension. On the contrary, the Model showed very good clinical accuracy [AUC= 0.825 (0.749-0.900), p<0.001]. CONCLUSIONS: Endocan and AOPP are independently correlated with hypertension in adult population and these tested markers together could be reliable parameters to discriminate patients with hypertension from normotensive ones.