Search Results (899)

Diabetes mellitus (DM) poses an increasingly high global health burden nowadays, while in adults, chronic kidney disease (CKD) associated with DM impacts 20–40% of those with the condition. Effective management of CKD in patients with diabetes necessitates a comprehensive, multidisciplinary approach. Numerous factors, including glomerular hyperfiltration, oxidative stress, inflammation, and hypoxia are linked to the advancement of diabetic kidney disease (DKD). Currently, no specific treatment for DKD has been established, prompting extensive exploration of new approaches. Renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter 2 inhibitors have demonstrated renoprotective effects in various human clinical trials. Additionally, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported as effective in managing DKD, while new therapeutic candidates are also under investigation, such as soluble guanylate cyclase activators and aldosterone synthase inhibitors. Recent evidence has shown that treating diabetic nephropathy by reducing albuminuria levels and retarding its progression is a complex skill. The purpose of this review is to support the impressive results that appear in reducing albuminuria and the progression of diabetic nephropathy with early and intensive combination treatment compared to the recently emerged conventional monotherapy, with agents that act on different pathophysiological mechanisms. Full article

Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (H₂O₂). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease—major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications. Full article

Background/Objectives: Chronic kidney disease (CKD) and diabetic kidney disease (DKD) are growing public health challenges. While diet and body composition influence metabolic and renal health, their combined role remains underexplored. This study investigates the association between the Planetary Health Diet Index (PHDI), body mass distribution, and the prevalence of CKD and DKD in U.S. adults. Methods: We analyzed data from 8093 adults aged ≥40 years from NHANES 2003–2018. PHDI was computed using two 24 h dietary recalls. Body composition was assessed using dual-energy X-ray absorptiometry (DXA), focusing on the android-to-gynoid fat ratio (AGFR) and lean mass ratio (AGLR). Survey-weighted linear and logistic regressions evaluated cross-sectional associations between PHDI score, body composition indices, and prevalence of CKD and DKD. Mediation analyses explored AGLR, AGFR, and body mass index (BMI) as potential mediators of the association between PHDI score and either CKD or DKD. Results: Higher PHDI scores were mildly associated with lower odds of CKD (OR per 10-point increase: 0.91; 95% CI: 0.83–0.99) and DKD (OR: 0.86; 95% CI: 0.76–0.97). Greater PHDI scores correlated with lower BMI, AGFR, and AGLR. Among participants with diabetes, AGLR mediated 17% of the relationship between a 10-point increase in PHDI score and decreased DKD prevalence, suggesting central lean mass distribution as a relevant pathway. No significant mediation was observed for AGFR, BMI, or for CKD. Conclusions: Adherence to PHD is associated with healthier body composition and lower prevalence of CKD and DKD. These findings support the promotion of dietary strategies that enhance metabolic and renal health in middle-aged and older individuals. Full article

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, characterized by progressive kidney dysfunction. Early detection and targeted therapies remain key challenges in managing DN. This study aims to identify proteomic alterations in DN patients compared to healthy controls, focusing on proteins involved in inflammation, oxidative stress, immune response, and metabolic dysregulation. Using mass spectrometry and advanced bioinformatics, we identified significant upregulation of proteins associated with platelet activation, immune regulation, and extracellular matrix remodeling, as well as downregulation of proteins linked to lipid metabolism, immune regulation, and structural stability. These findings highlight the molecular complexity of DN and suggest that altered protein expression plays a critical role in the progression of kidney damage. The identified proteins may serve as potential biomarkers for early diagnosis and therapeutic targets for DN. Our results underline the importance of proteomic analyses in advancing the understanding of DN pathogenesis and in developing strategies for personalized treatment to improve patient outcomes. Future research should focus on further elucidating these molecular mechanisms and their implications for clinical management. Full article

Chronic kidney disease (CKD) is a multifactorial disorder increasingly recognized as a systemic condition marked by persistent inflammation, oxidative stress, dyslipidemia, and endothelial dysfunction. Diabetic nephropathy, a leading cause of CKD, amplifies cardiovascular risk through intertwined mechanisms beyond traditional risk factors. This review synthesizes current evidence on the interplay between inflammation, oxidative stress, and atherosclerosis in CKD, with a special focus on emerging molecular biomarkers—PCSK9, EPHX2, AOPPs, and TBARSs—and their integration with clinical indices. These markers illuminate pathophysiological networks underlying CKD progression and cardiovascular complications, offering novel insights into risk stratification, disease monitoring, and targeted therapy. By exploring molecular and clinical intersections, this review underscores the potential of a personalized, biomarker-driven approach to CKD management. Full article

Background/Objectives: Microvascular complications are a major source of disability in type 2 diabetes mellitus (T2DM). We investigated whether body composition indices derived from multifrequency bioelectrical impedance analysis (BIA) independently predict neuropathy, retinopathy, nephropathy, and stroke, and whether they improve risk discrimination beyond the established clinical variables. Methods: In this cross-sectional analytical study (March 2024–February 2025), 124 adults with T2DM ≥ 12 months attending the outpatient diabetes clinic of the Universidad Técnica de Ambato (Ecuador) were enrolled. After an overnight fast and 15 min supine rest, thirteen whole-body BIA metrics including skeletal muscle mass (SMM), intracellular water (ICW), phase angle (PhA), and visceral fat area (VFA) were obtained with a segmental analyzer (InBody S10). Complications were ascertained with standard clinical and laboratory protocols. Principal component analysis (PCA) summarized the correlated BIA measures; multivariable logistic regression (adjusted for age, sex, diabetes duration, HbA1c, BMI, and medication use) generated odds ratios (ORs) per standard deviation (SD). Discrimination was assessed with bootstrapped receiver-operating characteristic curves. Results: The first principal component, driven by SMM, ICW, and PhA, accounted for a median 68% (range 65–72%) of body composition variance across all complications. Each SD increase in SMM lowered the odds of neuropathy (OR 0.54, 95% CI 0.41–0.71) and nephropathy (OR 0.70, 0.53–0.92), whereas VFA raised the risk of neuropathy (OR 1.55, 1.22–1.97) and retinopathy (OR 1.47, 1.14–1.88). PhA protected most strongly against stroke (OR 0.55, 0.37–0.82). Composite models integrating SMM, PhA, and adiposity indices achieved AUCs of 0.79–0.85, outperforming clinical models alone (all ΔAUC ≥ 0.05) and maintaining good calibration (Hosmer–Lemeshow p > 0.20). Optimal probability cut-offs (0.39–0.45) balanced sensitivity (0.74–0.80) and specificity (0.68–0.72). Conclusions: A lean tissue BIA signature (higher SMM, ICW, PhA) confers independent protection against neuropathy, retinopathy, nephropathy, and stroke, whereas visceral adiposity amplifies the risk. Because the assessment is rapid, inexpensive, and operator-independent, routine multifrequency BIA can be embedded into diabetes clinics to triage patients for early specialist referral and to monitor interventions aimed at preserving muscle and reducing visceral fat, thereby enhancing microvascular risk management in T2DM. Full article

Background: Type 2 diabetes mellitus (T2DM) increases sepsis risk due to immune dysfunction and chronic inflammation. Antidiabetic medications, while primarily used for glycemic control, may modulate sepsis susceptibility through immune and inflammatory pathways. This study investigates the association between antidiabetic medication use and sepsis risk in T2DM patients. Methods: A longitudinal cohort study was conducted using clinical registry data from 5009 T2DM patients at the University Hospital, Debrecen, Hungary (2016–2020). Sepsis cases were identified via ICD-10 code A41, and antidiabetic medication use was categorized using ATC codes. Baseline comorbidities and laboratory parameters were extracted. Chi-square and Wilcoxon rank–sum tests assessed associations between sepsis and categorical/numerical variables, respectively. Time-adjusted multivariate logistic regression evaluated predictors of sepsis risk, with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Results: Age, hypertension, ischemic heart disease, nephropathy, elevated blood glucose, C-reactive protein, and creatinine also independently increased sepsis risk. Insulin use was associated with a 2.6-fold increased sepsis risk (OR = 2.6, 95% CI: 2.09–3.34, p < 0.001), while SGLT2 inhibitors (OR = 0.56, 95% CI: 0.34–0.91, p = 0.02) and GLP-1 receptor agonists (OR = 0.39, 95% CI: 0.19–0.79, p = 0.009) were protective. Conclusions: Insulin-treated patients may require closer infection monitoring, while SGLT2 inhibitors and GLP-1 RAs could be prioritized in high-risk individuals. These findings highlight the potential to inform risk stratification and guide personalized antidiabetic therapy to reduce sepsis risk in T2DM. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the development of MASLD in T1D, as well as examining the relationship between MASLD and diabetes-related complications. We will also briefly discuss the prevalence, diagnostic challenges, associated complications, and potential mechanisms underlying MASLD in T1D. Although insulin resistance is well established in MASLD among those with type 2 diabetes, its role in T1D requires further clarification. Emerging markers, such as the estimated glucose disposal rate, offer early insight into this relationship. MASLD in T1D is linked to both microvascular and macrovascular complications, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Variability in prevalence estimates reflects inconsistencies among imaging modalities, emphasizing the need for standardized, non-invasive diagnostic approaches. Recognizing and addressing MASLD and its links to insulin resistance and diabetes complications in T1D is vital for mitigating long-term complications and enhancing clinical outcomes. Full article

Diabetes mellitus poses a significant global health challenge, primarily due to its chronic metabolic dysregulation, leading to widespread tissue and organ damage. This systemic impact results in a range of complications that markedly reduce patients’ quality of life. Therefore it is critical to understand the mechanisms underlying these complications. DJ-1 (also known as PARK7) is a highly conserved multifunctional protein involved in antioxidative defense, metabolic equilibrium, and cellular survival. Recent studies have highlighted that DJ-1 is critically involved in the pathogenesis and progression of diabetic complications, including macrovascular issues like cardiovascular disease and microvascular conditions such as diabetic nephropathy, retinopathy, and neuropathy, suggesting that it may serve as a promising therapeutic target. Importantly, drugs targeting DJ-1 have shown therapeutic effects. This review provides a comprehensive overview of the current under-standing of DJ-1’s role in diabetes-related complications, emphasizing recent research advances. Full article

Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for their renal and cardiovascular benefits. However, comparative real-world data on their long-term renal effectiveness remain limited. We conducted a retrospective, longitudinal study over a 2-year period to compare the impact of ARB monotherapy versus SGLT2i and angiotensin-converting enzyme inhibitor (ACEi) combination therapy on the progression of chronic kidney disease (CKD) in patients with DM. A total of 126 patients were included and grouped based on treatment regimen. Renal biomarkers were analyzed using t-tests and ANOVA (p < 0.01). Albuminuria was qualitatively classified via urinalysis as negative, level 1 (+1), level 2 (+2), or level 3 (+3). The ARB group demonstrated higher estimated glomerular filtration rate (eGFR) and lower serum creatinine (sCr) levels than the combination therapy group, with glycated hemoglobin (HbA1c), potassium (K⁺), and blood pressure remaining within normal limits in both cohorts. Albuminuria remained stable over time, with 60.8% of ARB users and 73.1% of combination therapy users exhibiting persistently or on-average negative results. Despite the expected additive benefits of SGLT2i/ACEi therapy, ARB monotherapy was associated with slightly more favorable renal function markers and a lower incidence of severe albuminuria. These findings suggest a need for further controlled studies to clarify the comparative long-term renal effects of these treatment regimens. Full article

Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: This narrative review aims to provide a comprehensive and critical synthesis of current evidence on the role of key interleukins in T1D and T2D, highlighting their immunological functions, genetic associations, clinical correlations, and translational potential. Methods: A targeted literature search was conducted in PubMed, Google Scholar, and ScienceDirect up to January 2025, focusing on English-language clinical and experimental studies involving interleukins and their relevance to T1D and T2D. Reference lists were manually screened for additional sources. Interleukins (ILs) were reviewed individually to assess their immunobiology, disease specificity, and biomarker or therapeutic value. Findings: Pro-inflammatory cytokines such as IL-1β, IL-6, and IL-17 contribute to islet inflammation, insulin resistance, and microvascular damage in both T1D and T2D. Anti-inflammatory mediators including IL-4, IL-10, and IL-13 exhibit protective effects but vary in expression across disease stages. Less-characterized interleukins such as IL-3, IL-5, IL-9, and IL-27 demonstrate dual or context-dependent roles, particularly in shaping immune tolerance and tissue-specific complications such as nephropathy and neuropathy. Polymorphisms in IL-10 and IL-6 genes further suggest genetic contributions to interleukin dysregulation and metabolic dysfunction. Despite promising insights, translational gaps persist due to overreliance on preclinical models and limited longitudinal clinical data. Conclusions: Interleukins represent a mechanistic bridge linking immune dysregulation to metabolic derangements in both T1D and T2D. While their diagnostic and therapeutic potential is increasingly recognized, future research must address current limitations through isoform-specific targeting, context-aware interventions, and validation in large-scale, human cohorts. A unified interleukin-based framework may ultimately advance personalized strategies for diabetes prevention and treatment. Full article

Quercetin (QE) is a naturally occurring flavonoid found in many fruits, vegetables, and other plant-based foods. It is recognized for its diverse pharmacological activities. Among its many therapeutic potentials, its antidiabetic properties are of particular interest due to the growing worldwide prevalence of diabetes mellitus. QE improves glycemic control by enhancing insulin sensitivity, stimulating glucose uptake, and preserving pancreatic beta cell function. These effects are mediated by the modulation of key molecular pathways, including AMPK, PI3K/Akt, and Nrf2/ARE, as well as by the suppression of oxidative stress and pro-inflammatory cytokines, such as TNF-α and IL-6. Furthermore, QE mitigates the progression of diabetic complications such as nephropathy, retinopathy, and vascular dysfunction, reducing lipid peroxidation and protecting endothelial function. However, the clinical application of quercetin is limited by its low water solubility, poor bioavailability, and extensive phase II metabolism. Advances in formulation strategies, including the use of nanocarriers, co-crystals, and phospholipid complexes, have shown promise in improving its pharmacokinetics. This review elucidates the mechanistic basis of QE quercetin antidiabetic action and discusses strategies to enhance its therapeutic potential in clinical settings. Full article

The renin–angiotensin–aldosterone system (RAAS) plays a central role in cardiovascular and renal homeostasis and is increasingly recognized for its broad immunomodulatory effects. Pharmacological RAAS inhibition, primarily via angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), has demonstrated therapeutic value beyond its use in hypertension and heart failure, extending to autoimmune, infectious, oncologic, and neurodegenerative conditions. ACEIs and ARBs modulate both innate and adaptive immune responses through Ang II-dependent and -independent mechanisms, influencing macrophage polarization, T-cell differentiation, cytokine expression, and antigen presentation. Notably, ACEIs exhibit Ang II-independent effects by enhancing antigen processing and regulating amyloid-β metabolism, offering potential neuroprotective benefits in Alzheimer’s disease. ARBs, particularly telmisartan and candesartan, provide additional anti-inflammatory effects via PPARγ activation. In cancer, RAAS inhibition affects tumor growth, angiogenesis, and immune surveillance, with ACEIs and ARBs showing distinct yet complementary impacts on tumor microenvironment modulation and chemotherapy cardioprotection. Moreover, ACEIs have shown promise in autoimmune myocarditis, colitis, and diabetic nephropathy by attenuating inflammatory cytokines. While clinical evidence supports the use of centrally acting ACEIs to treat early cognitive decline, further investigation is warranted to determine the long-term outcomes across disease contexts. These findings highlight the evolving role of RAAS inhibitors as immunomodulatory agents with promising implications across multiple systemic pathologies. Full article

Background: Semaglutide, a GLP-1 receptor agonist, has shown promising nephroprotective effects in clinical trials, though real-world data on its long-term impact on renal function in high-risk diabetic nephropathy patients remain scarce. Methods: We conducted a multicenter, retrospective observational study involving 156 patients with type 2 diabetes and chronic kidney disease (CKD) treated with subcutaneous semaglutide between 2019 and 2023. Inclusion required an eGFR > 15 mL/min/1.73 m² or albuminuria > 30 mg/g and at least two years of follow-up. The primary outcome was the change in eGFR slope after semaglutide initiation. Subgroup analyses were performed based on baseline eGFR, albuminuria, and SGLT2i co-treatment. Results: In the whole study population, the median eGFR slope significantly improved from −3.29 (IQR 7.54) to −0.79 (IQR 6.01) mL/min/1.73 m²/year post-treatment (p < 0.001). Multiple linear regression showed a hazard ratio for the effect of semaglutide on the eGFR slope of 4.06 (2.43–5.68), p < 0.001. In patients with baseline eGFR < 60 mL/min/1.73 m², the slope improved from −3.77 to −1.01 (p < 0.0001), while patients on concurrent SGLT2i therapy saw slope changes from −2.96 to −0.37 (p < 0.0001). Patients with albuminuria 30–1000 mg/g also improved from −2.96 to −0.04 (p < 0.0001); however, those > 1000 mg/g did not show a significant change (p = 0.184). Semaglutide also reduced BMI (p = 0.04), HbA1c (p = 0.002), triglycerides (p = 0.001), CRP (p = 0.003), and GGT values (p = 0.004). Conclusions: In real-world practice, semaglutide significantly attenuated renal function decline in high-risk diabetic patients, particularly those with advanced CKD or concurrent SGLT2i therapy. These findings support its nephroprotective role beyond glycemic control. Full article

Background: The atherogenic index of plasma (AIP), a prognostic indicator for cardiovascular disease, has not been fully explored in relation to clinical outcomes in patients receiving peritoneal dialysis. This study aims to elucidate the relationship between baseline AIP levels and all-cause mortality, cardiovascular mortality, and the peritonitis risk in this population. Methods: This retrospective cohort study included incident peritoneal dialysis patients in our center from 1 January 2006 through 31 December 2021. The end of the follow-up time was 31 December 2023. The participants were stratified by baseline AIP levels. Kaplan–Meier curves, Cox regression analyses, and subgroup analyses were used to evaluate associations with clinical outcomes. Results: The average age of the 2460 participants in this study was 45.9 years, and 1456 (59.2%) of them were men. Diabetic nephropathy (19.5%) was the second most common kidney disease, after primary glomerulonephritis (60.8%). The higher AIP tertile group was significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and peritonitis compared to the lowest AIP group, as evidenced by the Kaplan–Meier curves and the multivariate analyses. Continuous AIP levels also showed a positive correlation with the all-cause mortality and peritonitis risk, even after controlling for covariates. Conclusions: Our study highlights AIP as a predictive marker for adverse outcomes in PD patients, emphasizing its potential utility in risk stratification and clinical management. Full article