Search Results (1,646)

Background: Hip fractures represent a major public health challenge in aging populations and are associated with high morbidity, mortality, and healthcare costs. While osteoporosis is the main underlying cause, biochemical markers of bone metabolism may provide additional insight into skeletal remodeling processes. However, the relationship between bone turnover biomarkers and specific hip fracture patterns remains poorly understood. Methods: A retrospective observational study was conducted, including patients admitted with hip fractures between January 2022 and December 2023 at our institution. Serum levels of vitamin D, parathyroid hormone (PTH), N-terminal propeptide of type I collagen (PINP), and beta-C-terminal telopeptide of type I collagen (β-CTX) were analyzed. Fractures were classified as intracapsular or extracapsular. Continuous variables were compared using the Mann–Whitney U test. Multivariable logistic regression analysis was performed to identify factors independently associated with extracapsular fractures. Results: A total of 131 patients were included, comprising 57 intracapsular fractures and 74 extracapsular fractures. Patients with extracapsular fractures were significantly older (83 (75–89) vs. 80 (71–86) years; p = 0.0079). No significant differences were observed in vitamin D levels between fracture groups (p = 0.446). PTH levels were higher in extracapsular fractures (p = 0.030), while β-CTX levels tended to be lower (p = 0.080). In multivariable logistic regression analysis, age remained independently associated with extracapsular fracture pattern (OR 1.05, 95% CI 1.01–1.09; p = 0.03). Higher β-CTX levels were inversely associated with extracapsular fractures (OR 0.65, 95% CI 0.43–0.96; p = 0.03), whereas vitamin D levels were not independently associated with fracture type. Conclusions: Extracapsular hip fractures were primarily associated with older age in this cohort. Among bone metabolism biomarkers, β-CTX showed an inverse association with extracapsular fracture pattern after adjustment for confounding factors. These findings should be interpreted with caution and considered exploratory, highlighting the need for prospective studies to clarify their clinical significance. Full article

Background: Metabolic syndrome (MetS) is a cluster of pathologies (obesity, dyslipidemia, insulin resistance, hypertension) that affects over one quarter of old adults. MetS is a condition that markedly increases the susceptibility of various organs to dysfunctionality and is associated with the development of oxidative stress. The existing guidelines point out that exercise is highly advantageous for patients with MetS. However, there is a need for specific guidance and clinical evidence. Objective: This study aimed to investigate the effects of a moderate aerobic exercise program on older women without and with MetS. Methods: A total of 120 women aged 60–70 years old were recruited and divided into two groups: healthy old women (HOW, N = 60) and old women with MetS (OW-MetS, N = 60). Anthropometric values, biochemical parameters and markers of oxidative damage were evaluated before and after moderate aerobic exercise. Exercise was performed five days per week for three months (64 sessions). Each exercise session consisted of 40 min and included the following: (a) five minutes of warm-up exercise; (b) ten minutes of flexibility exercise with resistance using own weight and coordination; (c) twenty minutes of moderate-intensity aerobic exercise (heart rate max between 60% and 70%); and (d) five minutes to cool down/stretching with respiratory techniques. Results: A significant decrease in anthropometric variables was generated by the exercise program [waist circumference 4.35 cm (p < 0.05) in OW-MetS, body fat −1.55, −1.39% (p < 0.05) and muscle mass 0.8, 1.1% (p < 0.05) in HOW and OW-MetS, respectively]. The exercise program resulted in beneficial changes in all biochemical parameters in both groups. Importantly, HOMA values showed a significant decline of −0.85 and −6.17 in HOW and OW-MetS, respectively. Furthermore, oxidative stress was present in the OW-MetS group, which was reduced by the exercise program, resulting in a decrease in protein damage [formazan 45% and 42% in HOW and OW-MetS respectively] and an increase in antioxidant defenses (thiol groups 36%, 99% and GPx 55%, 20% in HOW and OW-MetS, respectively). Conclusions: The data of this study show that moderate aerobic exercise may be potentially useful in treating and preventing MetS in older patients. Full article

Background and Objectives: Major Depressive Disorder (MDD) and Bipolar Disorder (BD) lack objective molecular stratification despite partial clinical overlap, particularly during depressive phases. This cross-sectional study explored whether coordinated peripheral biomarker patterns could be identified using an integrated multivariate analytical framework. Materials and Methods: A total of 151 participants (MDD n = 41; BD n = 40; HC (healthy controls) n = 70) were profiled for 42 blood-derived parameters including composite inflammatory indices, hematological markers, trace elements measured by ICP-MS, and circulating BDNF and NLRP3 quantified by ELISA. Data were analyzed using univariate testing, unsupervised dimensionality reduction (PCA, t-SNE), and supervised classification (PLS-DA with cross-validation and permutation testing). Results: Thirty-seven of 42 parameters showed significant inter-group differences (p < 0.05). Circulating NLRP3 concentrations were markedly reduced in both psychiatric groups compared with HC. Composite inflammatory indices (NLR, SIRI, SII) were elevated in MDD. Zinc levels were modestly reduced, while manganese levels were increased in psychiatric cohorts. BDNF showed lower concentrations in MDD and higher concentrations in BD relative to HC. Cross-validated PLS-DA classification for psychiatric disorder vs. controls yielded an accuracy of 89.4% (AUC-ROC 0.947), with permutation testing indicating performance above chance. However, the sample-to-variable ratio and exploratory design warrant cautious interpretation. Conclusions: Multidomain peripheral biomarker profiling identified coordinated biochemical differences across diagnostic groups. These findings suggest the presence of multidimensional peripheral signatures associated with mood disorders within an exploratory framework. Full article

Background: Osteocalcin is a bone-derived protein traditionally regarded as a marker of bone formation, but experimental and clinical studies have suggested potential endocrine effects on energy and glucose metabolism. In pediatric populations, particularly in the context of obesity, the relationships between circulating osteocalcin, adiposity, and metabolic health remain inconsistent and poorly defined. Objective: To investigate associations between serum total osteocalcin and anthropometric, metabolic, biochemical, and body composition parameters in children and adolescents with obesity, with particular emphasis on adiposity and mineral metabolism. Methods: This retrospective cross-sectional study included 155 children and adolescents aged 4–18 years with obesity. Anthropometric measurements, laboratory parameters, and body composition assessed by dual-energy X-ray absorptiometry were extracted from medical records. Associations between osteocalcin z-scores and clinical variables were evaluated using linear regression models. Multivariable and extended regression models were applied to assess independent associations. Results: Osteocalcin was positively associated with markers of mineral metabolism, including serum 25-hydroxyvitamin D₃ (β = 0.19, p = 0.012), serum calcium (β = 0.19, p = 0.015), and free triiodothyronine (β = 0.32, p < 0.001) in multivariable analyses. No independent associations were observed between osteocalcin and measures of adiposity, including body mass index, visceral adipose tissue index, leptin, or markers of glucose and lipid metabolism. Conclusions: In children and adolescents with obesity, circulating osteocalcin is primarily associated with mineral metabolism rather than adiposity or metabolic health. These findings support the interpretation of total osteocalcin as a clinically accessible marker of bone turnover and mineral homeostasis rather than a robust surrogate of metabolic dysfunction in pediatric obesity. Full article

Innovation in the field of bioinspired therapeutic anticoagulants, as an alternative to heparin and its derivatives, is increasingly focused toward the discovery of new molecules from natural sources. Inspired by the compelling observation that marine organisms possess a wide array of acidic polysaccharides (APs) within their extracellular matrix (ECM) with promising anticoagulant potential, this study investigates AP topographic distribution, content, and bioactivity in the body of seven phylogenetically distant Mediterranean sponge species. Tissue architecture was evidenced by Alcian Blue histological staining whereas biochemical analyses were carried out on APs purified from papain-digested tissue extracts using anion-exchange chromatography. Four polysaccharide fractions were obtained and assessed for hexuronic acid content. The two most abundant ones, up to 98% of the total, were characterized by electrophoretic analyses, and assessed in vitro for inhibitory activity on blood coagulation. Histology evidenced a heterogeneous distribution of APs within the sponge’s ECM, along with marked interspecific variability in both concentration and electrophoretic profiles. Neither Tethya aurantium nor Crambe crambe showed any significant in vitro effects on coagulation, whereas the other species exhibited a strong inhibitory effect on both activated partial thromboplastin time (aPTT) and thrombin time (TT), comparable to standard heparin (Hep). Concerning aPTT, both I. retidermata and H. communis reached the endpoint of 300 s at 5 µgUA/mL, whereas S. spinosulus, O. lobularis, A. aerophoba reached it at 10 µgUA/mL. With reference to TT, A. aerophoba, I. retidermata, S. spinosulus and H. communis had comparable effects on coagulation time with respect to Hep (endpoint at 5 µgUA/mL), whereas O. lobularis was less effective (endpoint at 100 µgUA/mL). These findings show that Porifera, one of the most basal Metazoa, have an ECM rich in APs with anticoagulant properties towards both intrinsic and common pathways of coagulation, consistent with known inhibitory mechanisms reported for certain marine sulfated polysaccharides derived from other invertebrate taxa. These molecules, obtainable through sustainable blue technology, represent compelling candidates for bioinspired next-generation anticoagulant therapeutics, with broader applications in regenerative medicine and tissue engineering. Full article

Psychrophilic organisms are able to grow at temperatures down to −15 °C, while hyperthermophiles can multiply at temperatures up to 122 °C. What structural changes in extremophile proteins are needed to maintain stable and biochemically active structures under such conditions? Understanding how such extremophiles accomplish this is relevant for human health, biotechnology, and our search for life elsewhere in the universe. The purpose of the current study is to report and compare the structures of four rubredoxins (Rds), the first ever two experimental psychrophile bacteria structures (from Gram-positive Clostridium psychrophilum and Gram-negative Polaromonas glacialis) and two hyperthermophiles from the Gram-negative Thermotoga maritima bacterium and the archaeon Pyrococcus yayanosii, also a piezophile, as part of a program to understand structural variations that support both stability and function under extreme conditions. These structures were obtained using synchrotron radiation X-ray diffraction at 100 K. All four structures had the expected overall rubredoxin fold. Rubredoxin from the only aerobic psychrophilic bacterium Polaromonas glacialis had larger variations in sequence and structure, whereas the other psychrophilic bacterium showed properties closely related to hyperthermophile rubredoxins. Multi-subunit structures showed similar RMSD variability independent from their thermal adaptation status. We propose including functional information in the analysis since temperature optimization may not be the only determinant for a specific protein adaptation. Full article

Background/Objectives: Cardiovascular diseases are the leading cause of mortality worldwide, with coronary artery disease (CAD) being the most prevalent. An atherogenic diet contributes to oxidative stress by promoting lipid peroxidation in lipoproteins and cellular membranes, thereby compromising membrane integrity, which is reflected in lower phase angle (PhA) values. Dietary antioxidants play a crucial role in cellular health and in reducing atherosclerotic risk; therefore, the Dietary Antioxidant Index (DAI) is an important measure, as dietary antioxidants may counteract oxidative damage. This study aimed to assess the association between anthropometric, PhA, and biochemical variables across groups classified according to DAI. Methods: This was an analytical cross-sectional study. A total of 107 subjects, with and without CAD, were included. Oxidized LDL (oxLDL) and oxidized HDL (oxHDL) were determined using the ELISA technique. PhA was measured by bioelectrical impedance analysis, and DAI was calculated using the formula proposed by Wright et al. Results: DAI was positively associated with HDL concentrations in women with CAD, indicating that HDL levels increased by 5.8 mg/dL for each unit increase in DAI (R² = 0.625, p = 0.001). Furthermore, for each unit increase in DAI, the TC/HDL ratio decreased by 0.3 (R² = 0.625, p = 0.006), and the LDL/HDL ratio decreased by 0.2 (R² = 0.506, p = 0.012). Conclusions: A higher DAI is associated with a more favorable lipid profile in women with CAD, particularly with higher HDL concentrations and lower TC/HDL and LDL/HDL ratios. Full article

Hypovolemia is a systemic state characterized by severe reduction in the effective blood volume with subsequent tissue hypoperfusion. It may be due to fluid loss, decreased water intake, fluid redistribution, or systemic disease. The present study aimed to evaluate the diagnostic significance of the renal artery resistive index (RRI), caudal vena cava (CVC) diameter, and aorta (Ao) diameter in dogs with hypovolemia. For this purpose, 30 dogs (hypovolemic, n = 15; control, n = 15) were investigated. Clinical variables and hematological findings were investigated for each dog. Pulsed-wave Doppler ultrasound was performed to measure the RRI and diameters of the CVC and Ao. Ultrasound examination revealed a markedly elevated RRI (p < 0.001) and significantly reduced CVC (p < 0.001) and Ao (p < 0.001) diameters in hypovolemic dogs compared to controls, reflecting increased vascular resistance and impaired venous return. Biochemical analysis showed significant increases in blood urea nitrogen (BUN) and BUN:Cr ratio, while Cr remained unchanged. Hematological variables demonstrated limited diagnostic value, with only mild increases in packed cell volume (PCV%). Correlation analysis confirmed a strong positive correlation between RRI and BUN (r = 0.917; p < 0.01), RRI and BUN:Cr ratio (r = 0.664; p < 0.01), and CVC and Ao diameters (r = 0.832; p < 0.05). Receiver operating characteristic (ROC) analysis with area under the curve (AUC) identified RRI (AUC = 0.99), CVC diameter (AUC = 0.93), and Ao diameter (AUC = 0.88) as highly accurate markers of hypovolemia, whereas the CVC:Ao ratio and hematological markers provided poor discrimination. Logistic regression confirmed significant diagnostic value for RRI, CVC diameter, Ao diameter, and BUN, but final multivariate analysis revealed RRI as the sole independent early diagnostic marker (p < 0.001; OR: 196.0; 95% CI: 11.12–34.72). In conclusion, RRI measured by Doppler ultrasound is the most reliable and sensitive early diagnostic marker for hypovolemia in dogs, outperforming conventional biochemical and hematological markers. Full article

Background and Objectives: Percutaneous coronary intervention (PCI) has markedly improved outcomes in coronary artery disease through the implantation of bare-metal stents (BMS) or drug-eluting stents (DES). However, in-stent restenosis (ISR) remains a significant complication, often necessitating repeat interventions. This study aimed to identify risk factors associated with ISR in patients with ST-elevation myocardial infarction (STEMI) who underwent PCI. Materials and Methods: We conducted a retrospective, non-randomized observational study of 107 STEMI patients treated with PCI between January 2016 and December 2019 who subsequently underwent clinically indicated (predominantly symptom-driven) follow-up coronary angiography within 12 months. ISR was defined as ≥50% luminal narrowing at follow-up angiography. Time-to-event analysis was performed using Cox regression models, incorporating clinical, biochemical, and angiographic variables. Results: In this selected cohort of patients undergoing follow-up angiography, ISR of any degree was identified in 87% of patients, and 52% had restenosis >70%. Advanced age, prior cardiovascular events, diabetes mellitus, chronic kidney disease, and history of stroke significantly increased the hazard of ISR. Smoking, dyslipidemia, and hypertension were prevalent in patients with severe ISR. Women presented with more severe clinical profiles (higher Killip class and troponin levels). DES showed slightly better TIMI flow than BMS, but stent type, dimensions, and number did not significantly impact restenosis risk. Thrombolytic therapy was associated with a significantly reduced ISR hazard. Mortality was 6% in patients with severe ISR. The highest restenosis incidence occurred in the LAD and RCA territories. Conclusions: ISR is a multifactorial process influenced by demographic, clinical, and procedural factors. Despite technological advances, ISR remains a prevalent issue, particularly in high-risk groups undergoing clinically indicated follow-up angiography. Secondary prevention strategies, optimized stent deployment, and targeted therapies addressing inflammation and vascular remodeling are essential to improving long-term PCI outcomes. Full article

Background: Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype–phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study aimed to define the GCDH variant spectrum in GA1 patients with mild hepatopathy and assess genotype–phenotype correlations. Methods: We performed integrated clinical, biochemical, and molecular characterization of 15 unrelated patients with infantile-onset GA1. Whole-exome sequencing (WES) was performed for all participants, and the resulting data were compared with the reference sequence of the GCDH gene. Results: All patients presented within the first 6 months of life with macrocephaly, seizures, dystonia, and feeding difficulties. Neurological impairment and mild hepatopathy were variably observed, and one patient developed an acute encephalopathic crisis. Six homozygous GCDH variants were identified, predominantly missense. A common variant, c.541G>C (p.Glu181Gln), accounted for 73.3% of cases and defined a consistent phenotype of early macrocephaly and movement disorder with frequent mild hepatic involvement, suggesting regional enrichment and raising the possibility of a founder effect that warrants confirmation in future haplotype studies. A truncating variant, c.382C>T (p.Arg128Ter), was associated with severe early encephalopathy. Exon 6 represented a mutational hotspot. Biochemically, all patients showed elevated urinary glutaric and 3-hydroxyglutaric acids, increased glutarylcarnitine, and low-to-normal free carnitine, with higher metabolite levels in clinically more severe cases. All variants were pathogenic or likely pathogenic and extremely rare in population databases. Conclusions: This cohort reveals a striking predominance of the GCDH c.541G>C variant and establishes a clear biochemical signature with genotype-associated clinical patterns in infantile-onset GA1. These findings support a population-specific mutational spectrum, refine genotype–phenotype correlations, and underscore the importance of early molecular diagnosis to guide targeted neurological and hepatic monitoring as well as regional screening strategies. Full article

Botanical extracts have emerged as promising biostimulants in agricultural systems because of their ability to modulate key metabolic and redox processes in crops, thereby increasing stress tolerance and productivity. This review synthesizes current knowledge on how botanical extracts influence plant metabolism and redox homeostasis, with a particular emphasis on their role in adaptive cellular responses. Evidence indicates that these extracts can increase antioxidant enzyme activity, regulate reactive oxygen species (ROS) signaling, and promote the accumulation of bioactive metabolites associated with improved stress tolerance and enhanced growth. This review also examines how agronomic practices, including nutritional management, water availability, light regimes, and preharvest biostimulant applications, together with emerging biotechnological approaches, can be strategically employed to optimize the bioactive composition and efficacy of botanical extracts. By integrating recent advances in metabolomics and transcriptomics, the manuscript highlights the biochemical and molecular reprogramming triggered by botanical extracts. It identifies key challenges, including variability in extract composition, lack of standardization, and context-dependent responses. Finally, future research directions are outlined, emphasizing the need for mechanistic understanding, quantitative evaluation of plant responses, and the development of standardized frameworks to support the sustainable application of botanical extracts in agriculture. Full article

COASY-related disorders (CRDs) are a spectrum of autosomal recessive conditions caused by the dysfunction of CoA synthase, an enzyme responsible for the final steps of CoA synthesis. Clinical manifestations of CRDs are highly variable, ranging from perinatal lethal pontocerebellar hypoplasia to childhood-onset neurodegenerative brain iron accumulation, which is often recognized after clinical regression. Recent reports have described a few individuals with CRD who screened positive for carnitine palmitoyltransferase-I deficiency by newborn screening (NBS). However, heterogeneous clinical presentations, conflicting biochemical/molecular sequencing of CPT1A, and a lack of metabolic characterization have led to lengthy, costly diagnostic journeys. To address some of these aspects, this investigation retrospectively evaluated NBS acylcarnitine patterns in five CRD cases using Collaborative Laboratory Integrated Reports (CLIR). A total of 25 metabolites/ratios were identified to deviate significantly from reference ranges and were primarily composed of elevated free carnitine and reduced long-chain acylcarnitine levels. While low acylcarnitine concentrations are often not reported due to a lack of lower reference cutoffs, ratios involving these metabolites relative to short-chain acylcarnitines could aid in identifying CRD cases via NBS. When comparing this pattern to CPT-Ia cases, we confirmed a nearly identical acylcarnitine pattern between these, and thus support the need to consider CRD in cases with NBS results suggestive of CPT-Ia. This study is the first case series to characterize NBS patterns in patients with CRD and highlights the unique opportunity for early detection, particularly in cases that are neonatally asymptomatic and have unremarkable confirmatory biochemical results. Full article

Background: Discrepancies are frequently observed between liver steatosis grading assessed by conventional B-mode ultrasonography and vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). This study aimed to identify factors associated with these differences and to evaluate whether the two imaging methods provide comparable steatosis classifications. Methods: We conducted a retrospective cross-sectional observational study including 130 hospitalized patients evaluated over a two-year period who underwent laboratory testing, abdominal ultrasonography, and transient elastography. The analyzed variables included demographic characteristics, nutritional status, comorbidities, and biochemical parameters such as alanine aminotransferase (ALAT), total cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and the fibrosis-4 index (FIB-4). Patients were classified into two groups: concordant steatosis grading between the two methods (n = 61) and discordant results (n = 69). Results: Concordant steatosis grading was more frequently observed in patients with serum total cholesterol > 200 mg/dL (45.9%) and FIB-4 values between 1.45–3.25 (44.2%). A trend toward higher concordance was also observed in patients with elevated triglycerides. In contrast, viral liver disease was significantly associated with discordant results (26.2%). Higher fibrosis stages assessed by VCTE (F ≥ 2) and FIB-4 values > 3.25 showed a non-significant trend toward discordance. Conclusions: Several clinical and biochemical factors influence the agreement between ultrasound and VCTE-based CAP in the assessment of hepatic steatosis. Elevated cholesterol and intermediate FIB-4 values were associated with concordant results, whereas viral liver disease was associated with discordance between the two imaging modalities. Full article

Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a critical limitation of the current TSH-centric paradigm, which also fails to explain the heterogeneity in cardiometabolic outcomes observed among patients with similar biochemical profiles. Metabolomics, through the analysis of tissue-specific biofluids, could aid in capturing the complex metabolic perturbations that characterize this disease. In this review, we summarize metabolomic signatures typical of thyroid dysfunction, perform a critical evaluation of limitations and variability across studies, and explore the clinical and translational implications of metabolomics in thyroid pathology. In addition, five metabolic hubs influenced by thyroid hormone activity are summarized: (i) lipid and lipoprotein remodeling; (ii) mitochondrial energetics and redox balance; (iii) amino acid metabolism and protein turnover; (iv) gut–liver–thyroid axis and (v) biological impact of subclinical thyroid diseases. Taken together, these findings challenge the sufficiency of a diagnostic model based on TSH measurement and pose metabolomics as a promising tool to refine risk stratification, uncover subclinical vulnerability and guide patient-centered management of thyroid disease. Despite its promise, clinical adoption of metabolomics is hindered by a lack of standardization and complex data interpretation. To overcome these limitations, coupling metabolomics with genomics and transcriptomics may allow its translation into practical application. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article