Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant–antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a biomarker of inflammation. Results: Patients with DF had significantly higher (p < 0.05) PAB levels (170 ± 33.9 U/L) compared to those without DF complications (142 ± 31.3 U/L). In addition, patients with DF had significantly reduced SOD activities (p < 0.01). NLR values were significantly higher in the DF group (median: 2.8; interquartile range: 2.0–4.3) than in the group without DF (median: 1.4; interquartile range: 1.4–2.1; p < 0.01). A positive correlation was found between the PAB and NLR index (r = 0.449; p < 0.05). The diagnostic accuracy of both PAB (AUC = 0.741; p < 0.01) and NLR (AUC = 0.760; p < 0.01) was estimated as acceptable. Conclusions: In conclusion, the development of DF is associated with enhanced OS and inflammation processes. PAB and NLR could be useful non-invasive biomarkers of DF development.

Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs’ production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.

Different byproducts of oxidative stress do not always lead to the same conclusion regarding its relationship with cardiometabolic risk, since controversial results are reported so far. The aim of the current study was to examine prooxidant determinant ((prooxidant‐antioxidant balance (PAB)) and the marker of antioxidant defence capacity (total sulphydryl groups (tSHG)), as well as their ratio (PAB/tSHG) in relation to different cardiometabolic risk factors in the cohort of adult population. Additionally, we aimed to examine the joint effect of various cardiometabolic parameters on these markers, since to our knowledge, there are no studies that investigated that issue. A total of 292 participants underwent anthropometric measurements and venipuncture procedure for cardiometabolic risk factors assessment. Waist‐to‐height ratio (WHtR), body mass index, visceral adiposity index (VAI), and lipid accumulation product (LAP) were calculated. Principal component analysis (PCA) grouped various cardiometabolic risk parameters into different factors. This analysis was used in the subsequent binary logistic regression analysis to estimate the predictive potency of the factors towards the highest PAB and tSHG values. Our results show that triglycerides, VAI, and LAP were positively and high density lipoprotein cholesterol (HDL‐c) were negatively correlated with tSHG levels and vice versa with PAB/tSHG index, respectively. On the contrary, there were no independent correlations between each cardiometabolic risk factor and PAB. PCA revealed that obesity‐renal function‐related factor (i.e., higher WHtR, but lower urea and creatinine) predicts both high PAB (OR = 1.617, 95% CI (1.204‐2.171), P < 0.01) and low tSHG values (OR = 0.443, 95% CI (0.317‐0.618), P < 0.001), while obesity‐dyslipidemia‐related factor (i.e., lower HDL‐c and higher triglycerides, VAI, and LAP) predicts high tSHG values (OR = 2.433, 95% CI (1.660‐3.566), P < 0.001). In conclusion, unfavorable cardiometabolic profile was associated with higher tSHG values. Further studies are needed to examine whether increased antioxidative capacity might be regarded as a compensatory mechanism due to free radicals’ harmful effects.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a hepatic form of metabolic syndrome, often co-occurs with type 2 diabetes (T2D) and now affects approximately 30% of the global population. MASLD encompasses conditions from simple steatosis to metabolic dysfunction-associated steatohepatitis, with oxidative stress (OS) driving progression through inflammation. This study analyzes the expression levels of circulating miRNAs and redox status markers in MASLD patients with and without T2D, exploring their potential as disease biomarkers. The expressions of miR-21, miR-34a, and miR-122 were analyzed in the platelet-poor plasma of 147 participants, divided into three groups: MASLD + T2D (48), MASLD (50), and a control group (49). Total oxidant status (TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and superoxide anion radical (O₂^•−) were measured in serum and plasma. Logistic regression showed that miR-21, miR-34a, TOS, TAS, O₂^•−, and IMA were positive predictors of MASLD, while miR-21 and TAS were negative predictors of T2D in MASLD. Although miR-122 did not show a significant association with either condition, in combination with miR-34a and other markers such as lipid status and liver enzymes, a new significant predictor of MASLD was identified. Circulating miRNAs in combination with redox status markers, lipid status and liver enzymes show potential as MASLD biomarkers.

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM.

Background. Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID‐19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS‐CoV‐2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods. The prospective cohort study was performed on 98 COVID‐19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results. Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low‐density lipoprotein (oxLDL) and malondialdehyde levels and lower high‐density lipoprotein cholesterol (HDL‐C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions. Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID‐19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.