Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.

Background: Metabolic syndrome is a complex disorder characterized by the coexistence of multiple risk factors, including dysglycemia, hypertension, dyslipidemia, and visceral obesity. Both metabolic syndrome and diabetes mellitus are closely associated with the onset of microvascular complications such as retinopathy, polyneuropathy, and nephropathy. Methods: This narrative review analyzed 137 studies published up to 2025, retrieved from PubMed and Crossref databases. The objective was to identify and evaluate potential biomarkers that could facilitate the early detection of microvascular complications in patients with metabolic syndrome. Results: Several biomarkers demonstrated a strong correlation with microvascular complications in individuals with metabolic syndrome. These findings suggest their potential role in early diagnosis and risk assessment. Conclusions: The identification of reliable biomarkers may enhance early detection and targeted interventions for microvascular complications in metabolic syndrome. Further research is essential to validate these markers and establish their clinical applicability in routine medical practice.

Background: Diabetic autonomic neuropathy (DAN) is a severe complication of diabetes that affects the autonomic nervous system, impacting cardiovascular, gastrointestinal, genitourinary, and other systems. This study examines the levels of three potential biomarkers—DEFA1, progranulin, and NRG4—to assess their diagnostic and prognostic value in DAN patients. Methods: This observational, single-center study included 80 patients with type 2 diabetes. Clinical data and laboratory results were collected, and serum levels of DEFA1, progranulin, and NRG4 were measured using ELISA. The presence of DAN was assessed using Ewing’s tests. Statistical analyses included t-tests, Pearson’s correlations, and ROC analysis to explore associations and the predictive values of the biomarkers. Results: Progranulin levels were significantly elevated in patients with DAN compared to those without (p < 0.05), showing a positive correlation with diabetes duration (r = 0.375; p = 0.01) and a significant predictive value for DAN (AUC = 0.666; p = 0.013). DEFA1 and NRG4 levels did not differ significantly between the groups. Progranulin was also higher in patients who were treated with sulfonylureas and GLP-1 receptor agonists and in those with coronary artery disease. Conclusions: Progranulin emerges as a potential biomarker for the presence and severity of DAN, correlating with disease duration and autonomic dysfunction. While DEFA1 and NRG4 showed no significant association, the findings underscore the importance of further exploring the inflammatory pathways in DAN. Progranulin measurement could enhance early diagnosis and personalized management of autonomic neuropathy in diabetes.

Background/Objectives: Metabolic syndrome (MetS) is a complex, multifaceted disorder with significant socioeconomic and public health consequences, increasingly acknowledged as a global epidemic. Fibroblast growth factor 21 (FGF-21) is known to play a vital role in metabolic regulation; however, the precise roles and interactions of free fatty acids (FFAs) and insulin in influencing FGF-21 activity under both normal and pathological conditions are not yet fully understood. Meteorin-like protein (Metrnl) is a newly identified adipokine that appears to have the potential to regulate metabolic inflammation, which is a critical pathological factor in obesity and insulin resistance. Additionally, nesfatin-1, which is widely expressed in both central and peripheral tissues, is thought to be involved in various physiological functions beyond appetite control, such as glucose homeostasis, stress response, and cardiovascular health. Recent studies have indicated that sortilin may play a role in the pathophysiology of several metabolic disorders, including type 2 diabetes mellitus. Methods: This investigation was a cross-sectional study involving 200 individuals with obesity, which included both metabolically healthy obese participants and those experiencing obesity along with glycemic disorders. Serum levels of FGF-21, sortilin, Metrnl, and nesfatin-1 were measured using standardized enzyme-linked immunosorbent assay (ELISA) techniques. Results: The results indicated that FGF-21 levels were significantly elevated in patients with metabolic syndrome (p < 0.001), as well as those with insulin resistance (p = 0.009) and dyslipidemia (p = 0.03). Serum Metrnl levels were notably elevated in individuals meeting the criteria for insulin resistance, with a statistical significance of p < 0.001. Additionally, patients experiencing carbohydrate metabolism disorders exhibited significantly higher serum sortilin levels compared to those with normal blood glucose levels, with a p-value of 0.003. Conclusions: This research highlights FGF-21, Metrnl, nesfatin-1, and sortilin as potential biomarkers involved in the development of critical aspects of metabolic syndrome.

Background: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine associated with inflammation, metabolic dysfunction, and cardiovascular disease. Its role as a biomarker of microvascular complications in type 2 diabetes (T2D) remains incompletely defined. Objective: To evaluate circulating GDF-15 levels and their association with microvascular complications in patients with T2D. Methods: This cross-sectional study included 160 participants divided into three groups: T2D (n = 93), obesity without carbohydrate disorders (n = 36), and healthy controls (n = 31). Microvascular complications (neuropathy, nephropathy, retinopathy) were assessed. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed. Results: GDF-15 levels were significantly higher in T2D compared with non-diabetic individuals (267.5 ± 168.9 vs. 118.3 ± 55.5 pg/mL, p < 0.001). Higher GDF-15 was associated with neuropathy (odds ratio (OR) 1.985; 95% confidence interval (CI) 1.431–2.753) and nephropathy (OR 1.673; 95% CI 1.243–2.254) in unadjusted models. After adjustment, only nephropathy remained independently associated (OR 1.405; 95% CI 1.026–1.923). ROC analysis showed moderate discriminative ability for nephropathy (area under the curve (AUC) = 0.763). Conclusions: Circulating GDF-15 levels are significantly elevated in patients with T2D and are associated with microvascular complications, with the strongest independent association observed for diabetic nephropathy. These findings suggest that GDF-15 may represent a promising biomarker reflecting metabolic stress and risk of diabetic complications.

Background: Chronic low-grade inflammation plays a central role in the pathogenesis of type 2 diabetes (T2DM) and its complications. Neopterin, a marker of macrophage activation and Th1-mediated immune response, has been associated with cardiovascular disease and metabolic disorders. However, its relationship with diabetic autonomic neuropathy remains insufficiently investigated. Methods: We conducted a cross-sectional study including 129 participants (93 with T2DM and 36 with obesity without carbohydrate disturbances). Clinical, anthropometric, and biochemical assessments were performed. Cardiovascular autonomic neuropathy was evaluated using Ewing cardiovascular reflex tests and sudomotor dysfunction scoring. Neopterin concentrations were measured in serum. Correlation, ROC, and logistic regression analyses were performed. Results: Neopterin levels were not significantly different between T2DM and obesity groups. No differences were observed in patients with versus without peripheral neuropathy, nephropathy, or retinopathy. However, neopterin levels were significantly higher in individuals with cardiovascular autonomic neuropathy (p = 0.013). Neopterin correlated with cardiovascular autonomic neuropathy score, sudomotor dysfunction, fasting glucose, fasting insulin, and HOMA-IR. It showed a moderate negative monotonic correlation with eGFR (Spearman’s rho = −0.41, p< 0.001). In multivariable logistic regression adjusted for age, HbA1c, BMI, eGFR, and diabetes duration, each 1-SD increase in neopterin was associated with 2.67-fold higher odds of cardiovascular autonomic neuropathy (95% CI 1.21–5.89; p = 0.015). Conclusions: Circulating neopterin is independently associated with cardiovascular autonomic neuropathy in T2DM but not with classical microvascular complications. These findings suggest a potential role of immune-mediated mechanisms in the pathogenesis of diabetic cardiovascular autonomic neuropathy.