Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by high levels of low-density lipoprotein (LDL). This study aimed to identify variants in the LDLR, APOB, PCSK9 and LDLRAP1 genes and to identify the genotype–phenotype correlation in Serbian FH patients. Method: This study included a total of 101 patients suspected of having FH based on clinical criteria. Genetic analysis was performed by the next-generation sequencing (NGS) method. Results: An overall mutation detection rate of 43.6% was achieved. Thirteen distinct variants were detected in the LDLR gene (93.2%). The most frequently observed variant was c.858C>A p.(Ser286Arg), which was present in 26% of the LDLR-positive patients. Additional variants were detected in the APOB gene. No pathogenic variants were detected in the PCSK9 or LDLRAP1 genes. Comparing genetically FH-positive and FH-negative patients, statistical significance was observed in terms of age (p < 0.001), total cholesterol (TC) (p < 0.001), low-density-lipoprotein cholesterol (LDL-C) (p < 0.001) and triglyceridemia (p < 0.001). Conclusions: This study represents the first insight into the genetic basis of FH in Serbia. Taking into consideration that variants were detected in more than one gene and that the variants in the LDLR gene were distributed across nearly all exons, the FH diagnostics in Serbia ought to be based on NGS methodology.

Summary Background: We investigated the traditional and new bio- markers as predictors of cardiovascular mortality in the func- tionally disabled elderly who are living in a community. Methods: This prospective study included 253 participants (78.3% women) aged 65 and over who were monitored for 32 months. Receiver operating curve analysis and the Cox proportional hazard model were used to identify univariate and multivariate predictors of cardiovascular mortality. The Kaplan-Meier survival curve and Log rank test were used for survival analysis. Results: During the study, 43.1% participants died from car- diovascular diseases. Cutoff points of multivariate predictors were used to build a score system. The risk score was positive in patients with three or more of the following predictors: albumin 6.5 mmol/L and high-sensitivity C-reactive protein >2.25 mg/L. The rel- ative risk for cardiovascular mortality for someone with a positive vs. negative score was 3.91 (95% Cl: 2.55-5.98; P< 0.001). There was no change in risk after adjustment for age; sex, traditional cardiovascular risk factors, comorbidities and a number of disabilities. Conclusions: Presence of lo* grade inflammation, malnulri tion and early signs of renal dy sfunction are essential for car- diovascular risk among the functional disabled elderly and may be assessed using the proposed new inflammatory m3lnuhffion-renal involved score (1MRIS).

Optimized glycemic management is crucial for controlling atherosclerosis and consequent cardiovascular morbidity in patients with diabetes. Due to the continuous glucose burden from glucose-containing peritoneal dialysis (PD) solutions, PD patients with diabetes experience difficulties in glucose level regulation with glucose hypervariability and worsening dyslipidemia. Even in non-diabetic PD patients, glucose-containing PD solutions aggravate insulin resistance and cause overweight. Additionally, glucose degradation products (GDP) from glucose-based PD solutions provoke oxidative stress and complex inflammatory processes, leading to chronic deleterious and fibrotic peritoneal membrane changes. In this narrative review, we searched the literature using PubMed, MEDLINE, and Google Scholar over the last three decades to summarize the most important facts relevant to the presented issues, aiming to inform both endocrinologists and nephrologists in providing the best currently available care for people with diabetes on PD. We not only focus on adequate tailoring of insulin therapy adapted at the time of PD exchange with hypertonic glucose solution., but also emphasize the use of continuous glucose monitoring (CGM) that allows assessment of mean glucose values and time spent in normal, hypo, and hyperglycemia. However, the routine use of CGM in PD patients is limited due to high cost, and hemoglobin A1c (HbA1c) analysis is still recommended as a basic clinical tool for the assessment of glycemic control. Possible choices of antidiabetic drugs were considered given the narrowed choice due to contraindications for metformin and sulfonylurea. The other important therapeutic approach in PD patients with diabetes is using glucose-sparing PD regimens based on icodextrin and amino acid PD solutions with the addition of just one or two bags of low glucose concentration PD solution daily. This glucose-sparing approach not only reduces the glucose load and improves glycoregulation with correction of the lipid profile but also maintains the viability of the peritoneal membrane by reducing the harmful effects of GDPs.

Nogo (RTN4) proteins and their receptors have emerged as candidate mediators of metabolic regulation and vascular pathology relevant to type 2 diabetes (T2D). The primary objective of this PRISMA-guided systematic review was to evaluate the clinical and cohort evidence for RTN4/RTN4R as potential biomarkers of T2D progression and vascular complications. A secondary objective was to synthesize preclinical mechanistic evidence on the effects of Nogo axis modulation on pathways relevant to the pathogenesis of T2D. We performed a PRISMA-guided systematic review. The protocol was not prospectively registered in PROSPERO. To ensure reproducibility, we provide complete search keywords, the screening log and the full-text exclusion table. PubMed/MEDLINE, EMBASE and Web of Science were searched for studies published 2000–2025; full search keywords are provided in the main text. The search strategy combined and free-text terms with Boolean operators. We included original preclinical and clinical studies, cohort/proteomic analyses, meta-analyses, and mechanistic papers reporting expression, function, signaling, or clinical associations of Nogo proteins/receptors in metabolic or vascular outcomes. Exclusion criteria: non-English articles, unclear methods, studies outside 2000–2025, and studies lacking primary data. Two reviewers independently screened records; conflicts were resolved by consensus. Study quality was appraised using established tools (SYRCLE for animal studies, Newcastle–Ottawa Scale for cohort/case-control studies). Preclinical evidence supports tissue-specific roles for RTN4 isoforms and receptors in the regulation of insulin secretion, proGCG → GLP-1 processing, ER homeostasis, and vascular permeability through the Src/PI3K/Akt and RhoA/ROCK axes. Cohort and proteomic analyses report associations between RTN4/RTN4R or serum NogoB and faster progression of T2D or vascular complications, but genetic assessment of causality (Mendelian randomization) has so far provided limited support in available data sets. Findings are heterogeneous with respect to directionality and tissue localization. RTN4 signaling exhibits tissue-specific mechanisms relevant to glucose regulation and vascular biology and warrants further translational study. However, heterogeneity across studies and limited genetic support for causality indicate that isoform-specific quantitative validation, longitudinal cohorts and integrated genetic–functional analyses are required before RTN4/RTN4R can be considered as clinical biomarkers.

Background: Familial hypercholesterolemia (FH) is characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels and an increased risk of premature cardiovascular disease. The present study aimed to investigate the genetic background, associated biochemical profiles, clinical manifestations, and therapeutic response in patients with clinically suspected FH in Serbia. Methods: A total of 101 patients with clinically suspected FH were recruited from the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Serbia between 2015 and 2023. Clinical diagnosis was established using the Dutch Lipid Clinic Network (DLCN) criteria. Genetic profiles of all patients were previously determined using next-generation sequencing. Fasting serum lipids, apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB], and lipoprotein(a) (Lp(a)) were measured enzymatically. Levels of serum lipids were compared between genetically FH-positive (carriers of variants in LDLR, APOB, PCSK9 and LDLRAP1 genes) and FH-negative patients. Therapeutic response was assessed by achieving the LDL-C target level. Statistical analyses were conducted in SPSS (version 30.0). Results: Genetically confirmed FH patients exhibited significantly higher levels of ApoB (p=0.001) compared with variant-negative individuals, while ApoA-I (p=0.413) and Lp(a) (p=0.421) levels did not differ significantly between groups. Patients with pathogenic FH-associated variants were less likely to reach target LDL-C levels after therapy than those without identified variants. Conclusions: This study demonstrates biochemical diversity in familial hypercholesterolemia associated with genetic background in the Serbian population. Pathogenic FH mutations were associated with higher ApoB levels, underscoring the importance of combining genetic testing with lipid profiling for precise diagnosis and management.