Search Results (3,173)

Background: Non-proliferative diabetic retinopathy (NPDR) is a common microvascular complication of type 2 diabetes mellitus (T2DM) associated with chronic inflammation, metabolic dysregulation, and multiple interacting systemic factors. This study evaluated the associations of inflammatory biomarkers, serum 25-hydroxyvitamin D [25(OH)D], electrolyte homeostasis, and lipid-derived indices with NPDR. Methods: In this cross-sectional study with prospective recruitment, 98 patients with T2DM were classified into NPDR (n = 55) and non-DR (n = 43) groups. Clinical characteristics, hematological inflammatory indices, serum interleukin-6 (IL-6), C-reactive protein (CRP), 25(OH)D, electrolyte concentrations, lipid profile, and derived biomarkers—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), LDL-C/HDL-C ratio, and calculated serum osmolarity—were compared. Receiver operating characteristic (ROC) analysis and multivariable logistic regression were performed to assess discriminatory performance and independent associations with NPDR. Results: Patients with NPDR had significantly lower serum 25(OH)D concentrations than the non-DR group (16.6 ± 7.5 vs. 21.0 ± 5.2 ng/mL, p < 0.001). Serum IL-6 levels (4.2 ± 3.1 vs. 2.8 ± 1.4 pg/mL, p = 0.047), NLR (p = 0.043), LDL-C/HDL-C ratio (p = 0.031), and calculated serum osmolarity (p = 0.033) were significantly higher, whereas lymphocyte count and the lymphocyte-to-monocyte ratio were significantly lower. Among individual biomarkers, serum 25(OH)D showed the best discriminatory performance (AUC = 0.712). A multivariable model including insulin therapy, IL-6, serum 25(OH)D, and the LDL-C/HDL-C ratio demonstrated good discrimination (AUC = 0.813), with 81.8% sensitivity and 81.4% specificity. Bootstrap validation supported the stability of the model. Conclusions: NPDR was associated with lower serum 25(OH)D concentrations, systemic inflammation, and a less favorable LDL-C/HDL-C ratio. A multivariable model integrating inflammatory, metabolic, and nutritional biomarkers showed better discriminatory performance than individual biomarkers. The association between insulin therapy and NPDR likely reflects greater diabetes severity rather than a direct effect of insulin. These findings are exploratory, and prospective studies in larger independent cohorts are needed to determine whether these biomarkers improve risk stratification beyond established clinical factors. Full article

Background: Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are widely prescribed for type 2 diabetes mellitus (T2DM) because of their cardiovascular and renoprotective benefits. However, their use is associated with euglycemic diabetic ketoacidosis (EDKA), a rare but potentially life-threatening complication characterized by severe ketoacidosis despite relatively normal blood glucose levels. Failure to discontinue SGLT-2 inhibitors before surgery, as recommended in current guidelines, together with perioperative fasting and surgical stress, increases the risk of EDKA. Diagnostic complexity is compounded when concurrent postoperative surgical complications provide an alternative explanation for persistent metabolic acidosis. Methods: A 71-year-old man with T2DM receiving uninterrupted empagliflozin underwent direct lateral interbody fusion under general anesthesia. On postoperative day 2, he developed severe high anion-gap metabolic acidosis (pH 7.204, HCO₃⁻ 10.1 mEq/L) with near-normal blood glucose levels (178 mg/dL). Pneumoperitoneum identified on imaging was attributed to Hemovac drain-related peritoneal injury, and emergent laparoscopic exploration was performed under a working diagnosis of surgical sepsis. Although surgical source control was successfully achieved, severe metabolic acidosis persisted postoperatively (pH 7.275). Euglycemic diabetic ketoacidosis is an uncommon diabetic complication associated with several perioperative risk factors, including prolonged fasting and surgical stress. Subsequent serum ketone analysis demonstrated markedly elevated beta-hydroxybutyrate levels (4.8 mmol/L), confirming co-existing EDKA. Results: Following empagliflozin discontinuation, targeted treatment with concurrent insulin–dextrose infusion resulted in complete resolution of acid-base imbalance within five days. Conclusions: A concurrent surgical complication appeared to mask EDKA and contributed to a delay in its recognition. In patients receiving SGLT-2 inhibitors, metabolic acidosis that persists after an apparent surgical cause has been addressed should prompt measurement of serum ketones, irrespective of the blood glucose concentration. Structured perioperative protocols for SGLT-2 inhibitor management and postoperative ketone surveillance may help to prevent similar events. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a growing burden in low- and middle-income countries, and non-invasive risk tools have been proposed where laboratory screening is not feasible. Fast-and-frugal decision trees (FFDTs) are transparent, non-compensatory rules that make sensitivity–specificity trade-offs explicit. We asked how far five routinely collected sociodemographic cues can go for classifying self-reported diabetes status and benchmarked FFDTs against the simplest possible alternatives. Methods: A cross-sectional secondary analysis of the 2016 South Africa Demographic and Health Survey Adult Health recode (N = 10,292; 459 self-reported cases, 4.46%) was carried out. Five binary cues were derived: age category, household wealth, employment, education and sex. Data were split 70/30 into development and a locked hold-out set. Three purpose-specific FFDTs were selected by 5 × 10-fold cross-validation within the development data only, frozen, and then evaluated once on the hold-out set. Comparators were a pre-specified age-only rule and logistic regression using the same five predictors at a development-derived Youden threshold. We report survey-weighted estimates, internal–external cross-validation across nine provinces, external validation in 12 further DHS, subgroup performance, and a log–log analysis of error against training sample size. Results: On the hold-out set the balanced screening FFDT achieved sensitivity 0.920 (95% CI 0.862–0.959), specificity 0.585 (0.567–0.602) and balanced accuracy 0.752 (0.727–0.776). The pre-specified age-only rule achieved balanced accuracy 0.751 (0.724–0.775), while logistic regression at the development-derived Youden threshold achieved 0.766 (0.735–0.797). Across 50 independent splits, the case-finding FFDT was arithmetically identical to the age-only rule in every split; the balanced FFDT exceeded it by a median of 0.001 (95% range −0.004 to +0.025); the referral-minimisation FFDT was worse by a median of 0.124. Performance was stable across provinces (balanced accuracy 0.731–0.801) but degraded across countries (0.508–0.724), with referral rate ranging from 0.225 to 0.806. Error scaled with training size as beta = −0.044 (95% CI −0.063 to −0.025). Conclusions: Transparent decision trees built from non-invasive sociodemographic cues classify self-reported diabetes status no better than a single question about age, do not transport reliably across countries, and are unlikely to be materially improved by simply increasing the training sample size. Their value lies in auditability rather than accuracy. Progress in low-burden risk stratification for T2DM in these settings will require cues that carry a biological rather than health system signal. Full article

Background: Type 2 Diabetes Mellitus (T2DM) is associated with cognitive decline, potentially mediated by neuroinflammatory processes and altered neuroplasticity. This study investigated cerebrospinal fluid (CSF) biomarkers of neuroinflammation and neuroplasticity in T2DM individuals versus controls, and their relationship with cognitive performance. Methods: This cross-sectional study included 56 T2DM individuals and 26 controls (aged 37–70 years; 48% male). CSF concentrations of leptin, IL-6, VEGF, BDNF, TNF-α, IGF-1, and IL-1β were measured using ELISA. Cognitive function was assessed using MMSE, the Stroop test, SDMT, RCFT, and TAAV. Group comparisons used Mann–Whitney U or t-tests; Spearman correlations examined variable relationships. Results: No statistically significant differences in CSF biomarkers were observed between groups. However, T2DM patients showed lower word recall (4.66 ± 1.48 vs. 5.81 ± 1.52; p = 0.002), reduced Symbol–Digit performance (17.82 ± 12.16 vs. 24.92 ± 12.10; p = 0.016), and higher Complex Figure Test scores (19.94 ± 9.32 vs. 15.94 ± 5.02; p = 0.009). IL-6 was negatively correlated with MMSE (r = −0.33, p = 0.005). Significant correlations emerged between MMSE and Symbol–Digit scores (r = 0.40, p < 0.001) and among biomarkers. Conclusions: “No statistically significant differences in CSF biomarkers were observed between groups and unadjusted CSF biomarker concentrations did not differ significantly between groups; however, after adjustment for age and BMI, IL-6 was significantly elevated in T2DM patients, indicating that covariate-adjusted analyses may be more sensitive for detecting subtle neuroinflammatory differences in this population. Full article

Background/Objectives: Albuminuria is an important marker of kidney and cardiovascular risk in adults with type 2 diabetes mellitus (T2DM). Regional data from Mexico remain limited among patients with preserved estimated glomerular filtration rate (eGFR) and no previous diagnosis of diabetic kidney disease. This study aimed to describe albuminuria categories observed at a single screening assessment and to explore clinical factors associated with higher urinary albumin-to-creatinine ratio (uACR) categories in adults with T2DM receiving care at a regional hospital in western Mexico. Methods: This exploratory single-center cross-sectional study included 119 adults with T2DM (mean age, 53.3 ± 11.7 years), preserved eGFR (≥60 mL/min/1.73 m²), and no previous diagnosis of diabetic kidney disease. Albuminuria was classified from a single first-morning uACR measurement as A1 (<30 mg/g), A2 (30–300 mg/g), or A3 (>300 mg/g). Exploratory multivariable ordinal logistic regression evaluated factors associated with higher uACR categories. A secondary exploratory binary model evaluated screen-detected uACR ≥ 30 mg/g (A2/A3 versus A1). Results: A1 was observed in 67 patients (56.3%), A2 in 40 (33.6%), and A3 in 12 (10.1%); 52 patients (43.7%) had uACR ≥ 30 mg/g at screening. The median uACR was 25.6 mg/g, the median HbA1c was 11.2%, and the median fasting glucose was 280 mg/dL. In the exploratory ordinal model, longer T2DM duration (OR 1.51 per 5 years; 95% CI 1.09–2.10; p = 0.012), higher HbA1c (OR 1.18 per 1% increase; 95% CI 1.01–1.38; p = 0.036), and lower eGFR (OR 0.69 per 10 mL/min/1.73 m² increase; 95% CI 0.55–0.88; p = 0.003) were associated with higher uACR categories after adjustment for the measured covariates. In the secondary binary model, longer T2DM duration and lower eGFR were associated with screen-detected uACR ≥ 30 mg/g. Conclusions: A single screening assessment identified uACR ≥ 30 mg/g in 43.7% of this selected regional cohort. These findings represent screen-detected albuminuria and do not establish persistent albuminuria, diabetic kidney disease, temporality, or causality. Confirmation with repeated uACR measurements and validation in larger longitudinal multicenter studies with detailed medication data are required. Full article

Frailty is common among older adults with type 2 diabetes mellitus (T2DM). However, simple, objective, equipment-free screening tools for early frailty detection are limited. We evaluated the association between the objective one-leg standing test (OLST) and frailty in older male outpatients with T2DM and defined a clinically relevant OLST cut-off for frailty screening. Males aged ≥65 years with T2DM (n = 335) were included in this single-center, retrospective, cross-sectional study. Frailty was pre-categorized based on a Kihon Checklist (KCL) score ≥ 8. The association of OLST time with frailty was assessed by logistic regression. The Youden Index was used to determine the optimal OLST time cut-off. Frailty was observed in 17.3% of the participants. The KCL-frail group exhibited a shorter OLST time than the KCL-non-frail group (median: 12.1 [7.4–30.6] vs. 45.8 [23.2–60.0] s; p < 0.001). Shorter OLST time was independently associated with frailty (odds ratio 0.955 per 1 s increase; 95% confidence interval 0.939–0.971; p < 0.001). The optimal cut-off for identifying frailty was 34.1 s (area under the curve: 0.768). The OLST is an objective, equipment-free physical performance test that may complement subjective frailty screening to identify frailty in an ambulant male population aged ≥65 years with T2DM. Full article

Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of type 2 diabetes mellitus (T2DM) and a recognised marker of systemic vascular injury. Whether DR—graded independently by two experienced ophthalmologists as part of routine institutional care—is independently associated with concurrent nephropathy (urine albumin-to-creatinine ratio [UACR] ≥ 30 mg/g) and subclinical cardiac stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥ 125 pg/mL) remains insufficiently examined. Methods: Retrospective cross-sectional study of 401 T2DM adults who underwent dilated fundus examination independently graded by two board-certified ophthalmologists (each ≥ 10 years’ experience in diabetic eye disease) using ETDRS-based classification. Inter-physician agreement was quantified by Cohen’s weighted kappa. The primary composite outcome was concurrent nephropathy and subclinical cardiac stress. Multivariable logistic regression adjusted for age, sex, HbA1c, diabetes duration, eGFR, hypertension, and pharmacological treatments. Results: The composite outcome was present in 120 (64.2%) DR-positive vs. 14 (6.5%) DR-negative patients (crude OR: 25.59 (13.78–47.51); p < 0.001; fully adjusted OR: 21.49 (11.02–41.81); p < 0.001). Inter-physician agreement was high (Cohen’s weighted κ = 0.88; 95% CI: 0.83–0.93). Nephropathy alone was found in 164 (87.7%) vs. 76 (35.5%) patients (OR: 12.95 (7.71–21.75); p < 0.001), and elevated NT-proBNP in 137 (73.3%) vs. 39 (18.2%) patients (OR: 12.29 (7.65–19.76); p < 0.001). A significant trend across DR severity grades was observed (p for trend < 0.001), although the gradient was not strictly monotonic. ROC AUC = 0.837 (95% CI: 0.784–0.860). Conclusions: Ophthalmologist-graded DR was independently associated with the concurrent presence of albuminuria and elevated NT-proBNP in T2DM. Because the design is cross-sectional, these findings describe association rather than prediction or causation. They generate the hypothesis that retinal grading may help flag patients in whom cardiorenal biomarker assessment is worth considering, but prospective validation is required before any screening application. Full article

While glucose-driven mitochondrial dysfunction has been proposed to promote vascular dysfunction responsible for saphenous vein graft failure (VGF) following bypass surgery, the impact of type 2 diabetes mellitus (T2DM) on mitochondrial function in human saphenous vein smooth muscle cells (HSVSMCs) responsible for maladaptive remodelling is unknown. Our aim was to identify signalling pathways that mediate any mitochondrial dysfunction in HSVSMCs in vitro and assess the impact of T2DM. HSVSMCs explanted from surplus HSV tissues from consenting T2DM and non-diabetic patients undergoing coronary artery bypass graft surgery were treated with known activators and inhibitors of the JAK/STAT and MAPK/ERK pathways. Following this, real-time oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measures of mitochondrial function were then determined. Our findings revealed that both IL-6/sIL-6Rα trans-signalling complexes and platelet-derived growth factor-BB (PDGF-BB) significantly increased OCR in HSVSMCs from T2DM patients but not non-diabetic controls. Meanwhile, only PDGF-BB increased ECAR in HSVSMCs from T2DM patients but not in non-diabetic controls. The observed increases in OCR and ECAR were abolished by JAK1/2-selective inhibitor ruxolitinib. Furthermore, thrombin caused a significant increase in OCR, specifically in HSVSMCs from T2DM patients, and this effect was abolished by the MEK1/2-selective inhibitor trametinib. Both ruxolitinib and trametinib significantly reduced basal OCR and ECAR in HSVSMCs from both T2DM and non-diabetic patients. Together, these findings demonstrate a JAK/STAT- and MAPK/ERK-mediated regulation of mitochondrial function in HSVSMCs. As such, they represent potential targets for regulation of HSVSMC function that can be explored for drug development to limit saphenous VGF in T2DM. Full article

Non-communicable diseases (NCDs), including type 2 diabetes mellitus (DM), hypertension (HTA), obesity (OB), and cardiovascular disease (CVD), represent a major global health burden and disproportionately affect socially vulnerable populations. Small extracellular vesicles (EVs) are stable carriers of proteins and regulatory RNAs that may reflect endothelial dysfunction and cardiometabolic stress. This study explored plasma-derived EV-associated biomarkers in adults from La Guajira, Colombia, with emphasis on miR-126-3p, miR-21-5p, miR-92a-3p, and SNAIL. Anthropometric, clinical, and biochemical data were obtained from a cross-sectional cohort. Representative plasma samples were selected for EVs isolation by size-exclusion chromatography. Vesicles were characterized by nanoparticle tracking analysis, scanning transmission electron microscopy, protein quantification, Western blotting, and bead-based flow cytometry. Candidate miRNAs were identified by small RNA sequencing and validated by stem-loop RT-qPCR. Bioinformatic enrichment analyses were performed using miRNet 2.0 and KEGG pathway analysis. The epidemiological cohort showed a high cardiometabolic burden, with waist-to-height ratio (WHtR) and triglyceride-glucose (TyG) index emerging as key markers of central adiposity and metabolic dysfunction. Plasma-derived EVs displayed the expected nanoscale morphology and expressed canonical vesicle markers. Protein cargo analyses revealed EMT- and remodeling-associated proteins, including SNAIL and GAL-3. EV-associated miR-126-3p, miR-21-5p, and miR-92a-3p were enriched predominantly in hypertensive and hypertensive-diabetic groups. In an exploratory sub-cohort, CD31-positive EVs showed a trend toward increased expression in individuals with previous myocardial infarction or stroke (p = 0.057). KEGG enrichment analysis linked the identified miRNA signature to pathways involved in endothelial dysfunction, inflammation, vascular remodeling, apoptosis, and extracellular matrix organization. Plasma-derived EVs from individuals with cardiometabolic disorders carry molecular signatures consistent with endothelial stress and vascular remodeling. These findings identify miR-126-3p, miR-21-5p, miR-92a-3p, SNAIL, and CD31-positive EVs as exploratory candidate biomarkers that require validation in larger prospective cohorts. Full article

Diabetes mellitus (DM) induces significant endocrine disruption and oxidative stress (OS) within the testes, resulting in impaired spermatogenesis, increased sperm abnormalities, and compromised reproductive function. This study aimed to evaluate the combined protective effects of Semaglutide (SEM) combined with Carica papaya (papaya) juice against type 2 diabetes-induced testicular damage in rats. Forty adult male albino rats were divided into four experimental groups: a control group, a Streptozotocin (STZ)-induced diabetic group, a diabetic group treated with SEM (0.3 mg/kg), and a diabetic group treated with SEM (0.3 mg/kg) in combination with 10% papaya juice, administered for eight weeks. Statistically significant superiority over SEM alone was observed for selected endpoints; the findings primarily support the potential of papaya as a dose-sparing adjunct rather than demonstrating uniformly enhanced efficacy. They significantly improved systemic metabolic parameters, as evidenced by reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA_1c) levels and restoration of the lipid profile. Importantly, it also attenuated diabetes-induced testicular injury, as demonstrated by improved reproductive hormone levels, enhanced sperm parameters, restoration of antioxidant defenses, modulation of inflammatory and apoptotic signaling, and marked histopathological recovery of seminiferous tubular architecture. Antioxidant markers revealed a notable reduction in malondialdehyde (MDA) and cytochrome P450 2E1 (CYP2E1), along with significant increases in reduced glutathione, catalase (CAT), and superoxide dismutase (SOD). Furthermore, a marked modulation of key pro-inflammatory and pro-apoptotic mediators was observed, including forkhead box protein O1 (FOXO1), microRNA-155 (miR-155), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B cell subunit 1 (NF-κB1), interleukin-6 (IL-6), caspase-3 (CASP3), and BCL2-Associated X Apoptosis Regulator (Bax), while a significant upregulation of sirtuin-1 (SIRT1), microRNA-34c (miR-34c), and B-cell lymphoma-2 (Bcl-2) was also detected. Histopathological assessments confirmed the restoration of normal testicular architecture in the treated groups. These findings indicate that the combination strategy may have the potential to achieve dose savings while maintaining efficacy comparable to the standard-dose SEM, through the enhancement of the antioxidant defenses, modulation of inflammation, and apoptosis, specifically via the modulation of the miR-34c/miR-155 and SIRT1/FOXO1 signaling. Full article

Background/Objectives: Human islet amyloid polypeptide (IAPP) aggregation plays a critical role in the pathogenesis of type 2 diabetes mellitus (T2DM). Although metabolic alterations are a hallmark of T2DM, the functional roles of differential metabolites in regulating disease-associated molecular processes remain largely unexplored. This study aimed to establish a metabolomics-guided strategy for identifying endogenous metabolites with anti-amyloid activity and to investigate their underlying chemical interactions with IAPP. Methods: Untargeted metabolomic profiling of clinical samples from T2DM patients, obesity patients and healthy controls was performed to identify differential metabolites. Candidate metabolites were subsequently screened for their ability to modulate IAPP aggregation. Transmission electron microscopy (TEM), thioflavin T (ThT) fluorescence assays, and cell viability measurements were employed to evaluate their effects on fibril formation and cytotoxicity. Mass spectrometry was further used to characterize metabolite–IAPP interactions. Results: Metabolomic analysis identified 3-hydroxypyruvic acid (also known as β-hydroxypyruvic acid, hereafter referred to as HPA) as a significantly altered endogenous metabolite associated with T2DM and a candidate regulator of IAPP aggregation. Functional assays demonstrated that HPA effectively inhibited amyloid fibril formation, as evidenced by the absence of typical fibrillar structures and a prolonged lag phase during aggregation. HPA also significantly alleviated IAPP-induced cytotoxicity. Mass spectrometric analysis revealed the formation of HPA–IAPP oligomer complexes (n < 4), suggesting that HPA directly interacts with early oligomeric intermediates and interferes with their progression toward mature fibrils. Conclusions: This work demonstrates that untargeted metabolomics of clinical samples can serve as an effective strategy for discovering bioactive endogenous metabolites involved in disease-related molecular processes. The identification of HPA as a potential endogenous inhibitor of IAPP aggregation provides new chemical insight into the relationship between metabolic dysregulation and amyloidogenesis and highlights endogenous metabolites as a valuable source of potential therapeutic lead compounds. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) frequently coexist and are major risk factors for cardiovascular disease (CVD) and chronic kidney disease. Although the Mediterranean diet (MeDi) is widely recommended in cardiometabolic management, longitudinal real-world evidence regarding dietary adherence, body composition, and the role of continuous dietitian-led follow-up remains limited. Methods: This three-year prospective observational study included 158 adults with T2DM and AH treated at the Outpatient Clinic for Clinical Nutrition, University Hospital Centre Split, Croatia. Body composition was assessed using multi-frequency bioelectrical impedance analysis, dietary adherence using the Mediterranean Diet Serving Score (MDSS), and renal and metabolic parameters using standard laboratory methods. Participants were stratified according to attendance at scheduled dietitian-led follow-up visits. Results: Significant reductions were observed in body weight, body mass index (BMI), waist circumference, muscle mass, skeletal muscle index, and phase angle (PhA) during follow-up (all p < 0.001). Lipid profile improved, with reductions in total cholesterol and low-density lipoprotein levels and an increase in high-density lipoprotein concentrations. In contrast, renal function declined, as evidenced by increased creatinine and urea levels and decreased estimated glomerular filtration rate (eGFR). CVD incidence increased significantly during follow-up (p < 0.001). Although overall adherence to the MeDi improved, only 17.8% of participants achieved high adherence. Participants attending regular dietitian-led follow-up demonstrated significantly higher MDSS scores, greater adherence to the MeDi, and higher phase angle values compared with participants without regular follow-up. Conclusions: Adults with T2DM and AH demonstrated partial enhancement of MeDi adherence over three years; although the lipid profile also improved, this could not be attributed to diet and may largely reflect pharmacological treatment. These changes were accompanied by progressive muscle mass loss, declining renal function, and increased cardiovascular burden. Continuous dietitian-led follow-up was associated with superior dietary quality and better nutritional status, supporting the importance of individualized, multidisciplinary approaches integrating sustained nutritional counselling, lean mass preservation, and structured physical activity in long-term cardiometabolic care. Full article

Background: The transcription factor 7-like 2 (TCF7L2) gene is one of the strongest genetic determinants of type 2 diabetes mellitus (T2DM), with the rs7903146 (C > T) polymorphism consistently associated with impaired insulin secretion and glucose dysregulation. This study investigated the associations between the TCF7L2 rs7903146 polymorphism, glycemic control, oxidative stress biomarkers, and T2DM susceptibility, integrating bioinformatic analyses to explore the functional significance of this variant. Methods: This case–control study included 200 patients with T2DM, 100 prediabetic individuals, and 120 healthy controls. Genotyping of rs7903146 was performed using TaqMan SNP assays. Biochemical analyses included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipid profile, and oxidative stress biomarkers, including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA). Bioinformatic analyses included population frequency analysis, regulatory annotation, chromatin accessibility assessment, expression quantitative trait locus (eQTL) analysis, protein interaction network construction, and pathway enrichment analyses to investigate the functional consequences of rs7903146. Results: The T allele frequency was markedly higher in T2DM patients (33.5%) and prediabetic individuals (30%) than in controls (13.3%) (p < 0.001). T2DM susceptibility increased under allelic (OR = 3.27, 95% CI: 2.14–5.01), dominant (OR = 3.9, 95% CI: 2.37–6.42), and recessive (OR = 6.92, 95% CI: 1.59–30.07) models (p < 0.01). T2DM patients also showed significantly lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, lower total antioxidant capacity (TAC), and higher MDA levels (p < 0.001). T allele carriers had poorer glycemic control and greater oxidative stress. Bioinformatic analyses showed that rs7903146 resides within an active intronic regulatory region with chromatin accessibility, enhancer-associated histone marks, transcription factor occupancy, and candidate cis-regulatory elements. eQTL analyses showed tissue-specific effects on TCF7L2 expression, while network and pathway analyses highlighted WNT signaling, β-catenin transcriptional complexes, and metabolic regulation and oxidative stress pathways. Conclusions: The TCF7L2 rs7903146 polymorphism was significantly associated with T2DM susceptibility, impaired glycemic regulation, and altered oxidative stress biomarkers. Bioinformatic analyses provided predictive evidence suggesting that rs7903146 may have tissue-specific regulatory relevance and may be indirectly linked to metabolic and WNT/β-catenin signaling pathways. However, because of the observational case–control design, these findings do not establish causality, and the proposed regulatory mechanisms require experimental validation. Full article

Objective: Art therapy has been proposed as a complementary approach to support psychosocial well-being in chronic disease management, but patients’ understanding and perceived acceptability of art therapy in type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to describe item-level knowledge, attitudes, and art-related behaviors regarding art therapy among patients with T2DM in Nanjing, China, and to explore factors associated with willingness to try art therapy. Methods: A cross-sectional questionnaire survey was conducted from January to April 2025 among patients with T2DM receiving care at the Department of Endocrinology, Taikang Xianlin Drum Tower Hospital, Nanjing, China. Demographic characteristics and KAP related to art therapy for diabetes were collected. Univariable and multivariable logistic regression analyses were performed to explore factors associated with willingness to try art therapy. Results: A total of 982 patients with T2DM were included in the final analysis (mean age 50.61 ± 13.25 years; 662 (67.41%) male). Of these, 427 patients (43.48%) believed that art therapy is effective for diabetes, whereas 839 (85.44%) reported a willingness to try art therapy. In exploratory item-level analyses, patients who perceived art therapy as effective differed from those who did not across multiple knowledge, attitude, and behavior-related items. In multivariable logistic regression, lower willingness to try art therapy was associated with female sex (versus male, aOR = 3.914, 95%CI = 2.309–6.634), older age (aOR = 1.025 per year, 95%CI = 1.002–1.048), being a farmer or manual worker (versus teacher/cadre/medical staff, aOR = 2.129, 95%CI = 1.125–4.031), being unmarried/divorced (versus married, aOR = 9.961, 95% CI = 4.478–22.155), having out-of-province household registration (versus within province, aOR = 2.542, 95%CI = 1.333–4.850), being covered by employee/basic medical insurance (versus public expense or the new rural cooperative medical scheme, aOR = 1.961, 95%CI = 1.126–3.415), having chronic diseases (versus without chronic diseases, aOR = 2.495, 95% CI = 1.451–4.288), and frequent smoking (versus never smoking, aOR = 11.896, 95% CI = 5.555–25.477). Conclusion: Despite heterogeneous understanding of art therapy, most patients with T2DM reported willingness to try it, indicating generally favorable perceived acceptability. Future studies should examine how this stated willingness can be translated into informed participation in appropriately designed programs and evaluate their feasibility, uptake, and potential benefits. Full article

Background/Objectives: Asymptomatic hyperuricemia is a common yet frequently overlooked condition in the management of patients with type 2 diabetes mellitus (T2DM), despite its potential association with cardiovascular events. This study aimed to determine the prevalence and associated factors of asymptomatic hyperuricemia among patients with T2DM. Methods: A cross-sectional study was conducted on 235 patients with T2DM at a tertiary hospital. Demographic, clinical, laboratory, and medication data were collected. Asymptomatic hyperuricemia was defined as a serum uric acid level ≥ 420 µmol/L in men or ≥360 µmol/L in women, in the absence of clinical symptoms of gout. Hyperuricemia was classified by severity, and logistic regression analysis was used to identify associated factors. Results: The prevalence of asymptomatic hyperuricemia was 31.1%, including 25.9% with mild hyperuricemia (serum uric acid 420–540 µmol/L in men and 360–540 µmol/L in women) and 5.1% with severe hyperuricemia (serum uric acid > 540 µmol/L). Independent associated factors included body mass index (adjusted OR: 1.18; 95% CI: 1.01–1.36; p = 0.032), alcohol consumption (adjusted OR: 6.05; 95% CI: 1.79–20.41; p = 0.004), and lower estimated glomerular filtration rate (eGFR) (adjusted OR: 0.96; 95% CI: 0.93–0.99; p = 0.012). Subgroup analyses based on sex, renal function, and alcohol use demonstrated that these factors remained significant. The area under the receiver operating characteristic (ROC) curve for the predictive model was 0.869 (95% CI: 0.818–0.920). Conclusions: Asymptomatic hyperuricemia is prevalent in patients with T2DM (31.1%) and is associated with modifiable risk factors such as overweight, alcohol consumption, and chronic kidney disease. Our findings suggest that serum uric acid assessment may be useful as part of a comprehensive cardiovascular–renal–metabolic risk evaluation in patients with type 2 diabetes mellitus. However, prospective studies are needed to determine whether routine screening improves clinical outcomes. Full article