Search Results (1,199)

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease that necessitates individualized therapeutic strategies focusing on both glycemic control and the mitigation of comorbidities. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of modern treatment due to their unique renal mechanism of action. This review summarizes the metabolic mechanisms, pleiotropic effects, and clinical significance of SGLT2 inhibitors in the management of T2DM. This review provides an updated overview of the metabolic and systemic effects of SGLT2 inhibition. By promoting glycosuria, SGLT2 inhibitors induce a negative energy balance that contributes to modest weight loss, improved body composition, and beneficial alterations in lipid metabolism. Beyond their metabolic effects, accumulating preclinical evidence suggests that SGLT2 inhibitors exert anti-inflammatory and antifibrotic actions, partly through modulation of macrophage polarization and attenuation of oxidative stress. The clinical utility of SGLT2 inhibitors is highlighted through the review of major cardiovascular and renal outcome trials, which confirm significant benefits in reducing heart failure hospitalizations and slowing the progression of chronic kidney disease. Finally, we integrate these findings into the context of the latest international guidelines while addressing safety profiles, the rationale for combination therapies, and the transition toward a personalized, risk-based management approach in T2DM. Full article

Background: Heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) are common in the growing population of elderly patients, yet little evidence specifically targeting this population exists. The purpose of this study is to analyze the effect of SGLT2 inhibition in this cohort. Methods: A single-center, real-world observational study was performed. Patients aged >75 with HFrEF and CKD and theoretical indication for sodium–glucose cotransporter 2 (SGLT2) inhibitors were enrolled. Results: A total of 173 patients were included, with a mean age of 84.7 years, mean left ventricle ejection fraction of 29.5% and estimated glomerular filtration rate of 45.9 mL/min/1.73 m². During a median follow-up of 39 months, 73 (42.2%) deaths from any cause and 95 (53.3%) major clinical events (composite of mortality and heart failure admission) were recorded. Multivariate Cox proportional hazards regression analyses were performed to identify associated variables, and SGLT2 inhibition showed to be a protective factor for the mortality endpoint (hazard ratio 0.324 [0.117–0.894]). Male sex was shown to be a risk factor for both endpoints, diabetes mellitus for the mortality endpoint and diuretic use for the major clinical event endpoints. Conclusions: In a real-world study, treatment with SGLT2 inhibitors in elderly patients with HFrEF and CKD was associated with a lower rate of all-cause mortality. Full article

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and its co-occurrence with psychiatric disorders poses significant therapeutic challenges. This narrative review examines the safe use of psychopharmacological agents in patients with HF, focusing on mood stabilizers (particularly lithium) and antipsychotics. We summarize clinically relevant pharmacokinetic and pharmacodynamic interactions between these agents and guideline-directed HF therapies, including ACEIs, ARBs, ARNIs, beta-blockers, MRAs, SGLT2 inhibitors, and diuretics. Lithium is particularly prone to interactions due to its narrow therapeutic index and dependence on renal sodium handling, with RAAS inhibitors, thiazide diuretics, and SGLT2 inhibitors increasing the risk of toxicity. Antipsychotics are associated with QT prolongation, orthostatic hypotension, and electrolyte disturbances, with substantial variability between agents. This review highlights key clinical risks, provides a practical summary of drug interactions, and outlines principles for individualized, multidisciplinary management. Care requires coordinated cardiology–psychiatry collaboration, careful drug selection, and assessment of renal function, electrolytes, drug levels, and ECG parameters. Further studies and improved guideline integration are needed. Full article

Annona cherimola is a plant species widely used in Mexican traditional medicine, particularly in the management of diabetes. This study aimed to investigate the antihyperglycemic properties of the petroleum ether extract of A. cherimola leaves (PEEAcL), as well as to evaluate their effects on glycated hemoglobin and toxicity. In addition, the work was directed to determine its potential as an SGLT-1 and α-glucosidase inhibitor. The effect as a potential SGLT-1 and α-glucosidase inhibitor of PEEAcL was evaluated utilizing intestinal glucose absorption (IGA), oral glucose tolerance (OGT), oral sucrose tolerance (OST) and intestinal sucrose hydrolysis (ISH) tests. PEEAcL administered at doses of 200 mg/kg showed significant antihyperglycemic activity after 1 h of treatment, and the maximum effect was seen at 4 h in male and female diabetic mice. In the OST, OLT, and OGT tests, PEEAcL generated a reduction in the postprandial glucose peak at 2 h after the administration of a carbohydrate load, showing an effect comparable to that of acarbose and canagliflozin. In the IGA trial, PEEAcL significantly reduced glucose uptake in the small intestine. Similarly, in the ISH, PEEAcL recorded a significant reduction in glucose concentration in the external aqueous medium. Taken together, these results suggest that the antihyperglycemic effect of PEEAcL could be mediated, at least in part, by inhibition of SGLT-1 and the enzyme α-glucosidase. Full article

Chronic kidney disease (CKD) is a progressive global health challenge. While empagliflozin, a selective SGLT2 inhibitor, is known to attenuate CKD progression through mechanisms beyond glycemic control, the precise molecular pathways remain incompletely characterized and warrant further investigation. This study employed an integrated network pharmacology and molecular docking approach to elucidate the multi-target mechanisms of empagliflozin in CKD. Initial evaluation demonstrated that empagliflozin exhibits favorable physicochemical properties, drug-likeness, and ADMET profiles, supporting its potential as an effective orally administered therapeutic option for CKD management. Network analysis identified 221 shared molecular targets between empagliflozin and CKD-associated genes. Topological analysis of the protein–protein interaction (PPI) network revealed ten critical hub proteins—GAPDH, IL6, EGFR, HSP90AA1, NFKB1, HSP90AB1, MTOR, MAPK3, IL2, and PIK3CA—which serve as key regulators in CKD pathophysiology. Gene Ontology and KEGG pathway enrichment analyses indicated that these shared targets are significantly involved in phosphorylation, signal transduction, and central signaling cascades associated with CKD progression, including the PI3K-Akt, FoxO, HIF-1, and AGE-RAGE pathways. Molecular docking simulations corroborated empagliflozin’s multi-target affinity, demonstrating particularly strong binding energies toward HSP90AB1 (−10.85 kcal/mol), MAPK3 (−9.46 kcal/mol), and EGFR (−9.38 kcal/mol). Empagliflozin maintained stable hydrogen bonding throughout the 200-ns molecular dynamics simulation, primarily with GLN18, GLU42, SER45, ASN46, ASN101, GLY130, and TYR134, underscoring its persistent and well-anchored interaction with HSP90AB1. Collectively, these findings provide crucial mechanistic insights, suggesting that empagliflozin might exerts therapeutic effects by modulating interconnected pathways regulating inflammation, oxidative stress, and metabolic homeostasis, thereby reinforcing its role as a comprehensive, multi-target therapeutic strategy for CKD management. Nonetheless, validation through in vitro experiments remains necessary. Full article

Diabetic retinopathy (DR) is a common cause of vision loss in diabetes, and it often progresses without early symptoms. DR reflects injury of the retinal neurovascular unit (NVU), which includes neurons, Müller glia, astrocytes, endothelial cells, pericytes, and immune cells. Chronic hyperglycemia drives oxidative stress, advanced glycation end products–receptor for advanced glycation end products (AGE–RAGE) signaling, mitochondrial injury, and low-grade inflammation. These changes disrupt endothelial junctions, promote leukostasis, weaken pericyte support, increase basement membrane thickening, and lead to capillary dropout and hypoxia. Hypoxia-related signaling increases anti-vascular endothelial growth factor (VEGF) activity, which raises vascular leakage and supports neovascular disease. Glial stress and microglial activation add cytokines and reactive oxygen species, and neural dysfunction can appear early and can weaken neurovascular coupling. Modern diabetes care changes the short-term risk landscape because potent therapies can lower HbA1c quickly. Large and rapid HbA1c reductions can trigger early worsening of diabetic retinopathy (EWDR), mainly in patients with high baseline HbA1c and moderate-to-severe baseline DR. Semaglutide’s retinopathy complication signal in SUSTAIN-6 fits an EWDR-like pattern that tracks with rapid glycemic improvement in vulnerable eyes. In parallel, surgery adds acute stress, inflammation, glucose swings, hemodynamic shifts, and medication interruptions. These factors can worsen microvascular instability during recovery. Current perioperative guidelines and regulatory recommendations describe glucose targets and medication safety considerations, including preoperative interruption of SGLT2 inhibitors to reduce euglycemic ketoacidosis risk; however, the retina-specific implications of these measures remain indirect. This review summarizes current evidence linking NVU biology, EWDR risk, and perioperative diabetes-related factors. It discusses how these factors may interact in patients with diabetes and how they may influence retinal outcomes. The review is intended to synthesize current evidence and mechanistic interpretations rather than to provide formal clinical practice recommendations. Full article

Obesity drives chronic low-grade inflammation and endothelial dysfunction, key contributors to subclinical atherosclerosis. This review focuses on the netrin 1/UNC5B axis and its role in promoting macrophage retention within adipose tissue and atherosclerotic plaques, thereby perpetuating local inflammation and vascular injury. Complementary inflammatory markers—including IL 6, hsCRP, and IL 15—are discussed as indicators of systemic inflammatory burden, whereas endocan and ICAM 1 are briefly addressed as markers of endothelial activation. Among emerging pharmacological strategies, glucagon-like peptide-1 receptor agonists (GLP 1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) show the most consistent evidence for improving these biomarkers and reducing endothelial damage, with GLP 1RAs demonstrating direct effects on carotid intima–media thickness. Integrating biomarker profiling with obesity phenotypes may improve early risk stratification and support more precise management of subclinical atherosclerosis. Full article

Background/Objectives: Beyond glycemic control, oral antidiabetic drugs (OADs) may exert class-specific effects on muscle mass and hematologic parameters. However, real-world evidence comparing these effects across OAD classes remains limited. This study aimed to evaluate the differential effects of commonly prescribed OADs on skeletal muscle mass (SMM) and hemoglobin (Hb) levels in adults with type 2 diabetes mellitus (T2DM). Methods: In this prospective observational cohort study, 60 adults with newly initiated OAD therapy were followed for six months at a tertiary care center in Türkiye. Patients were classified according to the OAD class newly added to their regimen (metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, pioglitazone, or sodium–glucose cotransporter-2 inhibitors [SGLT2-i]). Multi-frequency bioelectrical impedance analysis was used to evaluate body composition, and hematologic parameters including Hb were obtained at both time points. To account for potential confounders—including age, sex, BMI, baseline Hb, and eGFR—binary logistic regression analyses were performed. Results: Patients initiated on pioglitazone (n = 11) demonstrated a borderline within-group increase in SMM in unadjusted analysis (median delta +0.17 kg, IQR −0.55 to +0.50; p = 0.050); however, this association was attenuated and no longer statistically significant after multivariable adjustment (OR 2.16, 95% CI 0.60–7.83; p = 0.240). In contrast, SGLT2-i users (n = 28) showed a significant increase in Hb (median delta +0.10 g/dL, IQR −0.30 to +0.50; p = 0.022), which remained significant after adjustment (OR 4.22, 95% CI 1.32–13.44; p = 0.015). Other OAD classes were not associated with meaningful changes in SMM or Hb. Conclusions: In this real-world prospective cohort, pioglitazone showed a trend toward increased SMM in unadjusted analysis that did not reach significance after adjustment, suggesting a hypothesis-generating signal warranting further investigation. SGLT2 inhibitors were independently associated with increased Hb levels, though the observed median increment was modest in absolute terms. These findings highlight potentially clinically relevant, non-glycemic effects of OAD classes and may inform individualized treatment selection, particularly in patients at risk of sarcopenia or anemia. Adequately powered, prospective studies are needed to validate and extend these preliminary observations. Full article

The integration of rooted plant flour into traditional noodle matrices, such as rice noodles and qingke noodles, represents a novel approach to enhancing the nutritional and sensory profiles of staple foods. This study investigates the volatile flavor components and functional compounds derived from rooted plant flours, including Gongmi “tribute rice”, qingke “highland barley” flour, kudzu vine flour, Gastrodia elata blume flour, dried ginger flour, and fishwort root flour, when incorporated into rice and qingke noodles. The novelty of this research lies in its comprehensive analysis of how these flours influence not only the nutritional and textural properties but also the volatile organic compounds (VOCs) that define sensory acceptance and health benefits. Using advanced gas chromatography mass spectrometry (GC-MS), we identified key VOCs, such as esters, aldehydes, and terpenes, which contribute to unique flavor profiles like umami, sweetness, and earthy notes in fortified noodles. Additionally, the study highlights the best functional compounds for health, including polyphenols, resistant starch, and polysaccharides, which demonstrate significant antioxidants, anti-inflammatory, and cholesterol-lowering properties. For instance, highland barley enriched flour exhibited high levels of phenolic compounds and carotenoids, which correlated with improved antioxidant activity and a reduced glycemic index. Similarly, Gongmi flour contributed elevated levels of γ-aminobutyric acid (GABA) and rutin, enhancing the rice noodles’ potential to manage metabolic diseases and support cardiovascular health. Molecular docking analyses predicted strong interactions between key volatile compounds (e.g., 3-dihydro-1, 3-trimethyl-33-phenyl-1H-indene) and metabolic targets like ACE and SGLT1, suggesting mechanisms for their cardioprotective and anti-diabetic effects. This research provides a groundbreaking framework for developing next generation functional foods by leveraging rooted plant flours to bridge the gap between sensory appeal and health efficacy, offering strategic insights for personalized nutrition and sustainable food production. Full article

Background: Cardiac involvement represents a major determinant of morbidity and mortality in patients with muscular dystrophies (MDs). Evidence supporting guideline-directed heart failure (HF) therapy in this population remains limited. We aimed to retrospectively assess the effectiveness and tolerability of sodium–glucose co-transporter 2 inhibitors (SGLT2i) in patients with MDs and a previous history of HFrEF, HFpEF and HFmrEF and/or echocardiographic evidence of an LVEF < 50% Methods: In this retrospective, single-center study, we enrolled consecutive patients with MD treated with empagliflozin or dapagliflozin between October 2021 and October 2024. Comprehensive clinical, laboratory, echocardiographic, and functional data were collected at a baseline (V1) and at follow-up (V3) visit to evaluate longitudinal changes. Results: Twenty-four patients (mean age 42 ± 16 years; 92% male) were included, with a median follow-up of 418 ± 104 days. SGLT2i therapy was well tolerated; one patient discontinued treatment due to a urinary tract infection. LVEF significantly improved from 41 ± 5% to 44 ± 6% (p = 0.005). FSS decreased from 36 to 30 (p < 0.001), indicating improved functional capacity. Background HF therapy was intensified over time, with increased prescription of mineralocorticoid receptor antagonists (21% vs. 52%; p = 0.039) and β-blockers (67% vs. 91%). The interval between MD diagnosis and cardiomyopathy onset independently predicted LVEF improvement (β = 0.17; p = 0.012). Conclusions: In patients with MDs and HF, SGLT2i therapy was safe and associated with a modest but significant improvement in LVEF, reduced fatigue, and enhanced prescription of guideline-directed HF therapy. These findings support the potential role of SGLT2i in this high-risk population and warrant confirmation in larger prospective studies. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice. Full article

Background/Objectives: Viral respiratory tract infections (VRTIs) in patients with diabetes mellitus (DM) are characterized by a severity gap rather than an infection gap. This review synthesizes evidence from the 2023–2026 respiratory seasons to provide a post-pandemic framework for managing the synergistic metabolic and viral threats in this population. Materials and Methods: A scoping review of literature from PubMed, Scopus, and Embase (2023–2026) was conducted, focusing on clinical outcomes and mechanistic interactions between DM and emerging respiratory pathogens. Results: Recent data identify human Metapneumovirus (hMPV) and adenovirus as significant threats to diabetic hosts, with mortality risks equivalent to seasonal influenza (HR 1.00 for hMPV vs. influenza). The two-hit model combines a baseline of innate immune paralysis, characterized by impaired neutrophil chemo-taxis and mechanical SP-D dysfunction, with a cellular signaling environment primed for cytokine overreaction by epigenetic metabolic memory. The stress hyperglycemia ratio (SHR) has emerged as a promising predictor of mortality compared to absolute glucose or HbA1c, with a proposed threshold of ≥1.14 identifying patients at 3.5-fold increased risk for mechanical ventilation. Precision management should consider the prudent suspension of SGLT2 inhibitors to mitigate euglycemic DKA risks and considering the early use of GLP-1 receptor agonists for their hypothesized pulmonary anti-inflammatory properties. Conclusions: Closing the mortality gap may require a shift from generic viral care to a precision model that treats metabolic susceptibility with high clinical priority alongside the treatment of the viral pathogen. Full article

Background/Objectives: While doxorubicin (DOX) and trastuzumab (TRZ) improve overall survival in women with breast cancer, these two anti-cancer drugs increase the risk of developing heart failure. As a novel and largely unexplored approach, our aim was to evaluate whether the prophylactic use of the sodium-glucose co-transporter 2 inhibitor empagliflozin (EMPA), with and without the angiotensin converting enzyme inhibitor perindopril (PER), is cardioprotective in preventing DOX + TRZ-mediated cardiotoxicity. Methods: In a chronic in vivo murine model, female mice received prophylactic treatment with PER (3 mg/kg), EMPA (10 mg/kg), or EMPA + PER via oral gavage for a total of 3 weeks as a run-in period prior to weekly administration of DOX + TRZ (8 mg/kg and 3 mg/kg, respectively) intraperitoneally for an additional 3 weeks (total of 6 weeks). Results: In mice treated with DOX + TRZ, the left ventricular ejection fraction (LVEF) decreased from 75 ± 2% at baseline to 40 ± 4% at week 6. Prophylactic treatment with either PER, EMPA, or EMPA+PER improved LVEF to 58 ± 3%, 66 ± 3%, and 67 ± 4% at week 6, respectively (p < 0.05). Histological analyses confirmed significant disruption of myofibrils, vacuolization, and loss of sarcomere integrity in the DOX + TRZ-treated mice. Prophylactic administration with PER, EMPA, or EMPA + PER, however, improved myofibril integrity at week 6 in mice receiving DOX + TRZ. Finally, although the Bax/Bcl-xL ratio was significantly elevated by 1.5-fold in mice treated with DOX + TRZ, this marker of apoptosis was attenuated by prophylactic treatment with either PER, EMPA, or EMPA + PER. Conclusions: Prophylactic administration of EMPA mitigated adverse cardiovascular remodeling in a chronic in vivo model of DOX + TRZ-mediated cardiotoxicity. 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