Background/Objectives: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease characterized by chronic hyperglycemia and progressive microvascular complications, including retinopathy, nephropathy, and neuropathy. While traditional markers like HbA1c capture average glycemic control, they often fail to predict microvascular damage risk. Glycated CD59 (GCD59), a complement regulatory protein modified under hyperglycemic conditions, has emerged as a promising biomarker reflecting complement dysregulation and endothelial injury. This study aimed to examine the relationship between plasma GCD59 levels and the presence of microvascular complications in patients with type 2 diabetes mellitus and to evaluate whether GCD59 shows potential for future use as a predictive biomarker, pending prospective validation. Methods: In this single-center, prospective case–control study, 246 participants were enrolled: 82 healthy controls, 82 T2DM patients without microvascular complications (DM − MC), and 82 T2DM patients with microvascular complications (DM + MC). Microvascular complications were defined based on standardized criteria for retinopathy, nephropathy, and neuropathy. Plasma GCD59 levels were measured using validated ELISA methods. Receiver operating characteristic (ROC) analyses, forest plots, and odds ratio calculations were employed to assess the discriminatory performance of GCD59. Statistical significance was set at p < 0.05. Results: Plasma GCD59 levels were significantly elevated across all diabetic groups compared to healthy controls (p < 0.001), with the highest levels in the DM + MC group (median 4.5 ng/mL) versus DM − MC (median 1.9 ng/mL) and controls (median 1.2 ng/mL). ROC analysis demonstrated excellent diagnostic performance for distinguishing DM + MC from healthy controls (AUC = 0.946, sensitivity 89%, specificity 97.6%) and good performance for distinguishing DM + MC from DM − MC (AUC = 0.849, sensitivity 72%, specificity 87.8%). Forest plot analyses confirmed significantly elevated odds ratios for GCD59 across all microvascular subgroups. Importantly, GCD59 levels correlated positively with inflammatory markers (CRP, ESR, leukocyte count), suggesting a combined role of complement dysregulation and chronic inflammation in diabetic microangiopathy. Conclusions: Plasma GCD59 may be a promising biomarker for identifying T2DM patients who may be at increased risk for microvascular complications, independent of conventional glycemic markers. Given the cross-sectional design of this study, causal inference is not possible; prospective validation is required. The observed strong discriminatory performance highlights potential future clinical utility, pending further validation of diagnostic thresholds, assay standardization, and feasibility in routine care settings.

Background/Objectives: Erectile dysfunction (ED) is a common complication of diabetes mellitus (DM), largely attributable to vascular, neurological and metabolic dysfunctions. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation and endothelial dysfunction, both of which play key roles in ED pathophysiology. This study aimed to evaluate the relationship between serum suPAR levels and ED in patients with type 2 DM, assessing its potential as a biomarker for early detection. Methods: This prospective, cross-sectional study included 127 male patients with type 2 DM and 46 healthy controls. Erectile function was assessed using the International Index of Erectile Function-5. Patients were divided into three groups: controls, diabetic patients without ED (DM-NoED) and diabetic patients with ED (DMED). Serum suPAR levels were measured via ELISA. Statistical analyses included Kruskal–Wallis tests, Dunn’s post hoc comparisons and ROC curve analysis to evaluate diagnostic performance. Results: Serum suPAR levels were significantly elevated in the DMED group compared to both the DM-NoED and control groups (p < 0.001). The median suPAR levels were 107.9 pg/mL (controls), 130.3 pg/mL (DM-NoED) and 218.7 pg/mL (DMED). ROC analysis revealed an AUC of 0.836 in distinguishing DMED from DM-NoED with 87.5% sensitivity and 79.2% specificity. Conclusions: Elevated serum suPAR levels are significantly associated with ED in men with type 2 DM, independent of glycemic control and conventional cardiovascular risk factors. These findings suggest that suPAR may be a promising biomarker for the early detection and risk assessment of ED in diabetic patients. Future prospective studies are needed to confirm its clinical utility.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major metabolic disorder associated with progressive microvascular complications such as nephropathy, retinopathy, and neuropathy. Early detection of diabetic nephropathy (DN) remains challenging, as conventional markers such as urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are influenced by non-renal factors and lack sensitivity for subclinical injury. Sirtuin 2 (SIRT2), a cytoplasmic NAD⁺-dependent deacetylase involved in oxidative stress and inflammatory regulation, has recently been implicated in renal pathophysiology. This study aimed to assess the relationship between serum SIRT2 levels and the presence of diabetic nephropathy and to evaluate its potential utility as a complementary biomarker reflecting early renal injury. Methods: In this single-center, cross-sectional study, 180 participants aged 18–80 years were enrolled: 60 healthy controls, 60 T2DM patients without nephropathy (T2DM − DN), and 60 T2DM patients with nephropathy (T2DM + DN). Serum SIRT2 concentrations were quantified using a validated ELISA. Group comparisons, multinomial logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to assess associations between SIRT2 and renal indices (UACR and eGFR). Statistical significance was set at p < 0.05. Results: Serum SIRT2 concentrations showed a progressive elevation across study groups (p < 0.001), with median levels of 6.13 ng/mL in healthy controls, 8.53 ng/mL in T2DM − DN, and 33.19 ng/mL in T2DM + DN. ROC analysis revealed good diagnostic performance for differentiating DN from healthy controls (AUC = 0.813, sensitivity 75%, and specificity 78.3%). Multivariable regression analysis identified SIRT2 as an independent correlate of DN after adjusting for metabolic and renal covariates (adjusted OR = 1.22, 95% CI 1.11–1.35, p < 0.001). Conclusions: Serum SIRT2 levels were observed to increase in parallel with the presence and severity of diabetic nephropathy and remained independently associated with the condition after adjustment for conventional risk factors. These findings suggest that SIRT2 may serve as a feasible complementary biomarker reflecting renal injury processes not captured by traditional measures. Further longitudinal studies are warranted to clarify its prognostic significance and potential for clinical integration.

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune disorder characterized by chronic inflammation and metabolic alterations. Mitochondria-derived peptides (MDPs), particularly mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c), have emerged as key regulators of cellular metabolism, insulin sensitivity, oxidative stress, and inflammatory responses. This study aimed to investigate the association between circulating MOTS-c levels and HT and to explore its potential role in thyroid autoimmunity and metabolic regulation. Methods: In this cross-sectional study, patients diagnosed with HT (n: 90) were compared with age- and sex-matched healthy controls (n: 90). Results: A total of 180 participants were included, comprising 90 patients with HT and 90 age- and sex-matched healthy controls. Circulating MOTS-c levels were significantly lower in patients with HT compared to controls (p < 0.001). MOTS-c levels demonstrated significant inverse correlations with body mass index, fasting glucose, HbA1c, HOMA-IR, thyroid-stimulating hormone, C-reactive protein, and thyroid autoantibody levels (all p < 0.05). In subgroup analyses, these associations remained significant within the HT cohort, particularly for HOMA-IR and thyroid autoantibodies. Multivariable regression analysis identified HT (β = −30.04, p < 0.001) and HOMA-IR (β = −0.85, p < 0.001) as independent determinants of reduced circulating MOTS-c levels. Levothyroxine (LT4) use was not associated with significant differences in MOTS-c concentrations. Conclusions: Circulating MOTS-c levels are markedly reduced in patients with HT and are independently associated with insulin resistance and autoimmune burden. These findings suggest that impaired mitochondrial signaling may play a role in the pathophysiology of thyroid autoimmunity and highlight MOTS-c as a promising biomarker linking metabolic dysfunction and immune dysregulation.

Background and Objectives: Diabetic retinopathy (DR) is a leading microvascular complication of type 2 diabetes (T2D). Fractalkine (CX3CL1), a chemokine involved in inflammation, angiogenesis, and microglial activation, may play a role in DR pathogenesis. This study investigated the association between serum fractalkine levels, the presence of DR, and disease severity. Materials and Methods: In this cross-sectional study, 140 adults with T2D were classified as non-DR (n = 32) or DR (n = 108) according to ICDR and ETDRS criteria; DR cases were further categorized into NPDR (n = 76) and PDR (n = 32), with NPDR staged as mild, moderate, or severe. Serum fractalkine concentrations were measured using ELISA. Results: Serum fractalkine levels were significantly higher in patients with DR than in those without retinopathy (0.7 vs. 0.4 ng/mL, p < 0.001). Within NPDR stages, fractalkine levels were highest in severe NPDR (p = 0.004). No significant fractalkine difference was found between NPDR and PDR groups. In multivariable analysis, serum fractalkine (OR 10.2; 95% CI 1.2–89.6; p = 0.036) remained independently associated with the presence of DR. For identifying DR, fractalkine yielded an AUC of 0.736; the optimal cut-off of 0.455 ng/mL provided 81.5% sensitivity and 56.3% specificity. In distinguishing severe NPDR, fractalkine demonstrated strong diagnostic performance (AUC = 0.784), with a cut-off of 0.720 ng/mL yielding 100% sensitivity and 61.9% specificity. Conclusions: Serum fractalkine is significantly associated with both the presence and severity of DR and remains independently associated with retinopathy after adjustment for traditional risk markers. Serum fractalkine may offer complementary systemic information in automated and AI-based retinal screening. These findings are exploratory and hypothesis-generating, and prospective studies are required to determine the clinical relevance of serum fractalkine in DR.

Osteoarthritis (OA) is increasingly recognized as a metabolically influenced inflammatory disease, particularly in the context of obesity. Wnt1-inducible signaling pathway protein 1 (WISP1), a downstream mediator of Wnt/β-catenin signaling, has been implicated in adipose tissue inflammation and cartilage remodeling; however, clinical data regarding circulating serum WISP1 levels in obesity-associated OA remain limited. This study aimed to investigate the relationship between serum WISP1 concentrations and OA status in obese adults. This cross-sectional study included 180 participants classified into three groups: healthy non-obese controls (n = 60), obese individuals without OA (n = 60), and obese individuals with OA (n = 60). Clinical, anthropometric, metabolic, and inflammatory parameters were recorded. Serum WISP1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Group comparisons, correlation analyses, logistic regression models, and receiver operating characteristic (ROC) analyses were performed. Serum WISP1 concentrations differed significantly among groups, showing a stepwise increase from healthy controls to obese OA (–) and obese OA (+) participants (p < 0.001). WISP1 remained independently associated with osteoarthritis among obese individuals after adjustment for age, sex, body mass index, HOMA-IR, diuretic use and C-reactive protein (OR 1.003; 95% CI 1.001–1.005). Although obese participants demonstrated adverse metabolic and inflammatory profiles compared with controls, most metabolic parameters did not distinguish OA subgroups within obesity. ROC analysis demonstrated good discriminatory performance of WISP1 for distinguishing obese OA (+) from obese OA (–) groups (AUC 0.807, 95% CI 0.727–0.879, p < 0.001). Serum WISP1 concentrations are elevated in obese individuals with osteoarthritis and are independently associated with OA status beyond conventional measures of adiposity and systemic inflammation. These findings suggest that WISP1 may serve as a potential biomarker associated with metabolic–inflammatory processes. Given the cross-sectional nature of the study, the observed findings should be interpreted as associations, and causal relationships cannot be inferred. Further longitudinal and externally validated studies are needed to clarify its clinical utility and biological significance.