Background: Selenium (Sel) supplementation has been proposed as an antioxidant adjunct in Graves’ orbitopathy (GO), with early randomized evidence suggesting benefits in quality of life (QoL), ocular involvement, and disease progression in mild GO. However, subsequent trials across populations with different Sel status and disease severity have yielded inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) reassessed the efficacy of Sel supplementation in GO. Methods: PubMed, Scopus, and the Cochrane Library were searched from inception to 1 May 2026 for RCTs, comparing Sel supplementation with placebo or no Sel supplementation in patients with GO (PROSPERO “CRD420261395074”). Heterogeneity was assessed using I² statistics and Cochran’s Q test. Risk ratios (RRs) were calculated using the Mantel–Haenszel method, and mean differences (MDs) using the Inverse-Variance method. Random-effects models with restricted maximum-likelihood estimation were applied. Results: Five RCTs including 303 patients were analyzed, of whom 165 (56%) received Sel. Sel supplementation was associated with a significant reduction in clinical activity score (MD −1.05; 95% CI −1.61 to −0.48; I² = 52%; p < 0.01). No significant differences were observed in palpebral aperture (MD −0.12; 95% CI −1.22 to 0.98; I² = 58%; p = 0.83), although this anatomical parameter should be interpreted cautiously because it may be influenced by thyroid functional status and hyperthyroidism-related Müller muscle hyperfunction. No significant differences were observed in QoL improvement (RR 1.72; 95% CI 0.43 to 6.92; I² = 86%; p = 0.24) or visual function (MD 6.31; 95% CI −1.40 to 14.03; I² = 45%; p = 0.11). Conclusions: Sel supplementation may improve clinical activity score in patients with Graves’ orbitopathy, but this finding should be interpreted cautiously given the small number of trials, limited sample size, and clinically relevant heterogeneity. Current evidence does not show consistent benefits for palpebral aperture, quality of life, or visual function. Larger RCTs stratified by baseline Sel status and disease severity are needed before firm conclusions can be drawn.

Background: Inflammation plays a key role in the pathogenesis of type 2 diabetes (T2D) and the associated cardiovascular complications. High-sensitivity C-reactive protein (hsCRP) is a widely used marker of systemic inflammation as well as a predictor of cardiovascular risk. Objective: There is increasing evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, may have effects on hsCRP levels, independent of their effects on glycemic control and body weight loss. This purpose of our study is to explore the effect of semaglutide on hsCRP levels in patients with type 2 diabetes. Additionally, we aimed to determine whether the observed effect of semaglutide on hsCRP is fully mediated by changes in HbA1c and body weight, or whether there is a direct effect suggesting the presence of an independent anti-inflammatory mechanism. Methods: The study included 70 outpatients with diagnosed type 2 diabetes undergoing therapy with metformin and/or a sulfonylurea. Semaglutide was added to the existing therapeutic regimen. All participants were followed up after a 6-month a period. At the beginning and at the end of the study, the hsCRP values, some selected indicators of glycemic control, and the anthropometric measurements were recorded. Results: The mean hsCRP value at baseline was 4.90 ± 1.21 mg/L, while after six-month therapy, it dropped to 2.23 ± 2.21 mg/L. Conclusions: The results of the analysis have a good potential to contribute to a better understanding of the pleiotropic effects of GLP-1 RAs and support the hypothesis of a direct anti-inflammatory role of semaglutide, which could have clinical significance in the context of cardiometabolic risk management in patients with type 2 diabetes.

Inflammation plays a key role in the pathogenesis of type 2 diabetes (T2D) and the associated cardiovascular complication. High-sensitivity C-reactive protein (hsCRP) is a widely used marker of systemic inflammation as well as a predictor of cardiovascular risk. There is increasing evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, may have effect on hsCRP levels, independent of their effects on glycemic control and body weight loss. This purpose of our study is to explore the effect of semaglutide on hsCRP levels in patients with type 2 diabetes. Additionally, we aimed to determine whether the observed effect of semaglutide on hsCRP is fully mediated by changes in HbA1c and body weight, or whether there is a direct effect suggesting the presence of an independent anti-inflammatory mechanism. The study included 66 outpatients with diagnosed type 2 diabetes undergoing therapy with metformin and/or a sulfonylurea. Semaglutide was added to the existing therapeutic regimen. All participants were followed up for 6 months period. Respectively, at the beginning and at the end of the study, the hsCRP values, some selected indicators of glycemic control as well as the anthropometric measurements were recorded. The mean hsCRP value at baseline was 4.90±1.21 mg/L, while after six-month therapy it dropped to 2.23±2.21 mg/L. The results of the analysis have a good potential to contribute to better understanding of the pleiotropic effects of GLP-1 RAs and support the hypothesis of a direct anti-inflammatory role of semaglutide, which could have clinical significance in the context of cardiometabolic risk management in patients with type 2 diabetes.

Background: Sarcopenic obesity is increasingly recognized as a complex metabolic condition characterized by the coexistence of excess adiposity and reduced skeletal muscle mass and function. Postmenopausal women are particularly vulnerable to sarcopenic obesity due to hormonal alterations, chronic low-grade inflammation, vitamin D deficiency, and insulin resistance. However, limited data are available regarding the interrelationships between sarcopenic obesity, vitamin D status, and metabolic dysfunction in Bulgarian postmenopausal women with type 2 diabetes mellitus (T2DM). Aim: The present study aimed to investigate the associations between sarcopenic obesity, serum vitamin D concentrations, and insulin resistance in Bulgarian postmenopausal women with T2DM. Materials and Methods: A cross-sectional observational study was conducted at Medical Center Prime Clinic during the period from January 2024 to December 2025. A total of 240 postmenopausal women aged 50-75 years were enrolled, including 120 women with T2DM and 120 apparently healthy postmenopausal controls. Anthropometric measurements, body composition parameters, handgrip strength, fasting glucose, insulin, glycated hemoglobin (HbA1c), lipid profile, inflammatory biomarkers, and serum 25-hydroxyvitamin D [25(OH)D] concentrations were evaluated. Insulin resistance was assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Results: Women with T2DM demonstrated significantly higher body mass index, waist circumference, fasting glucose, HbA1c, HOMA-IR, and hsCRP levels compared with controls (p<0.001). In contrast, serum 25(OH)D concentrations, skeletal muscle mass, and handgrip strength were significantly lower in diabetic women (p<0.001). Sarcopenic obesity was identified more frequently in the T2DM group compared with controls (42.5% vs. 16.7%, p<0.001). Serum vitamin D concentrations correlated negatively with BMI (r = -0.41), waist circumference (r = -0.45), HOMA-IR (r = -0.48), and hsCRP levels (r = -0.37), while positive correlations were observed with skeletal muscle mass (r = 0.39) and handgrip strength (r = 0.43) (all p<0.001). Multiple regression analysis identified sarcopenic obesity, serum vitamin D concentration, waist circumference, and hsCRP as independent predictors of insulin resistance.

Gestational diabetes mellitus (GDM) is increasingly recognized as a heterogeneous metabolic disorder comprising pathophysiological phenotypes that differ in their underlying mechanisms, clinical presentation and long-term outcomes. While pregnancy-induced insulin resistance remains the predominant pathogenic mechanism, a subset of women develops hyperglycemia largely because of reduced pancreatic β-cell reserve accompanied by islet autoimmunity. This autoimmune phenotype links gestational diabetes with autoimmune diabetes, but its boundaries and clinical significance remain incompletely defined. We aimed to review current knowledge of the autoimmune phenotype of GDM, with focus on immune pathophysiological mechanisms, biomarkers, clinical characteristics and implications for precision medicine, and to distinguish findings demonstrated directly in GDM from mechanisms extrapolated from type 1 diabetes (T1D). This narrative review was based on a structured PubMed/MEDLINE search from database inception through the end of October 2026, supplemented by targeted searches, manual screening of reference lists, and relevant clinical guidelines and consensus documents. Evidence obtained directly in women with GDM was considered alongside selected mechanistic literature from T1D and adult autoimmune diabetes. In some women with GDM, islet autoantibodies are associated with impaired β-cell function and an increased risk of autoimmune diabetes after delivery. The cellular mechanisms underlying these associations remain insufficiently studied in GDM. Pregnancy may act as a physiological metabolic stress test that exposes previously compensated β-cell dysfunction associated with islet autoimmunity, although its influence on the underlying autoimmune process remains uncertain. Islet autoantibodies are enriched among women with GDM, but their frequency varies widely between populations and assays and is lower after delivery than during pregnancy. The number and persistence of antibodies, particularly when combined with reduced endogenous insulin secretion, carry considerably more prognostic weight than a single positive result. Cellular immune mechanisms are well characterized in T1D but remain largely unvalidated in GDM. Recognition of the autoimmune phenotype extends the concept of GDM beyond a purely glucose-based classification. It is best viewed as a spectrum ranging from isolated seropositivity to pregnancy-unmasked autoimmune diabetes rather than as a uniform independent entity. A phenotype-oriented approach combining clinical features, autoantibody profiles and measures of β-cell function may facilitate earlier recognition of women at risk and more individualized follow-up, but universal autoantibody screening and antibody-specific treatment are not currently supported.

Introduction: Remogliflozin is a sodium–glucose cotransporter-2 inhibitor used for type 2 diabetes mellitus (T2DM), but its overall efficacy and safety remain fragmented. This updated systematic review and meta-analysis evaluated the efficacy and safety of remogliflozin using evidence exclusively from randomized controlled trials (RCTs). Methods: PubMed; Scopus; and the Cochrane Library were searched from inception to 15 July 2026 for RCTs lasting at least 12 weeks that compared remogliflozin or a remogliflozin-containing regimen with placebo; usual care; or another glucose-lowering treatment in adults with T2DM (PROSPERO: CRD420261462138). Risk ratios (RRs) were calculated using the Mantel–Haenszel method and mean differences (MDs) using the inverse-variance method. Random-effects models with restricted maximum-likelihood estimation and Hartung–Knapp adjustment were applied. Heterogeneity was assessed using I² and Cochran’s Q test. Results: Nine RCTs involving 1731 participants were included, of whom 906 (52.3%) received remogliflozin or a remogliflozin-containing regimen. Across heterogeneous comparator regimens, remogliflozin-containing treatment strategies were associated with lower HbA1c (MD −0.40 percentage points; 95% CI −0.63 to −0.16; I² = 59.9%; p < 0.01) and body weight (MD −2.15 kg; 95% CI −3.26 to −1.03; I² = 56.5%; p < 0.01). No statistically significant differences were detected for fasting plasma glucose (MD −6.84 mg/dL; 95% CI −16.07 to 2.38; I² = 59.4%; p = 0.150), total adverse events (RR 1.16; 95% CI 0.93–1.43; I² = 0%; p = 0.155), or hypoglycaemia (RR 0.89; 95% CI 0.28–2.81; I² = 0%; p = 0.696); however, the safety estimates, particularly for hypoglycaemia, were imprecise. Conclusions: Across heterogeneous randomized comparisons, remogliflozin-containing treatment strategies were associated with modest reductions in HbA1c and body weight, whereas the effect on fasting plasma glucose remained inconclusive. The available evidence was insufficient to establish whether total adverse events or hypoglycaemia differed between treatment groups because of the small evidence base, short follow-up, sparse events, and imprecise estimates.