Background/Objectives: Metabolic syndrome (MetS) is a major global public health concern associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Iron metabolism has been implicated, but the storage (ferritin) and functional (soluble transferrin receptor, sTfR) axes are rarely assessed within a single model. We aimed to determine whether both axes are independently associated with glycaemia and MetS and to evaluate their diagnostic value. Materials and Methods: A cross-sectional study was conducted in 297 adults (72.8% women) from Turkestan, Kazakhstan. Hierarchical regression models with sequential adjustment were applied for age, sex, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), dietary inflammatory index (DII), HFE H63D genotype, and gamma-glutamyl transferase (GGT). Path analysis and receiver operating characteristic (ROC) analysis were also performed. Results: Ferritin and sTfR were independently associated with fasting glucose (β = 0.27 and 0.73, respectively) and metabolic syndrome (OR = 1.52 and 4.53, respectively). When analyzed separately, neither biomarker reached statistical significance for MetS (ferritin: OR = 1.20, p = 0.140; sTfR: OR = 1.93, p = 0.072). Ferritin demonstrated no discriminatory ability in men (AUC = 0.500, 95% CI 0.370–0.630) and modest discrimination in women (AUC = 0.652, 95% CI 0.571–0.732). GGT accounted for approximately 28% of the ferritin–glucose association in a path-analytic model. Ferritin, GGT, and HbA1c levels increased progressively even among individuals with 0–2 MetS components. Conclusions: Both the storage and functional axes of iron metabolism provide independent information on glycaemic status, but their associations become apparent only when assessed simultaneously. Ferritin alone is not suitable as a diagnostic marker for metabolic syndrome.

Background: Insulin resistance (IR) is a major pathogenic factor in metabolic syndrome and related diseases. It is challenging to accurately measure IR due to high cost and technical complexity. TyG-derived indices have been proposed as simple and reliable surrogates for assessing insulin resistance. The present study aimed to investigate the association between TyG-derived indices and indicators of mineral metabolism and bone quality and to examine sex-specific differences. Methods: This cross-sectional study included 330 adults aged 18–65 years. Age-adjusted partial correlation analyses and multivariable linear regression models were performed to examine the associations between TyG indices and several metabolic parameters, minerals, and QUS bone indices. Results: TyG–BMI was strongly correlated with triglycerides (females: r = 0.51; males: r = 0.54, both p < 0.001), glucose (females: r = 0.54, p < 0.001), and hip circumference (females: r = 0.77; males: r = 0.58, both p < 0.001). HDL showed inverse associations (females: r = −0.41, p < 0.001). In females, TyG–BMI demonstrated modest positive correlations with bone parameters, including BQI (r = 0.21, p = 0.002), T-score and Z-score (r = 0.21, p = 0.002 for both), SOS (r = 0.19, p = 0.007), and BUA (r = 0.18, p = 0.010), whereas no significant associations were observed in males. In multivariable models, TyG–BMI in females remained independently associated with glucose (β = 9.77, p < 0.001), waist circumference (β = 2.94, p < 0.001), and HDL (β = −26.6, p < 0.001), but not with mineral or bone parameters. Conclusions: The TyG-derived indices, most notably TyG–BMI, are useful indicators of metabolic status that correlate with bone quality yet exhibit sex-specific associations. These findings support the role of TyG-derived indices as accessible surrogate markers of metabolic status and demonstrate sex-specific associations with bone quality parameters.

Background/Objectives: In resource-limited regions, limited access to genetic testing may delay etiological diagnosis in selected patients with epilepsy and complex neurological manifestations, particularly when the phenotype raises suspicion of an underlying genetic etiology. This study aimed to assess the diagnostic value and clinical utility of phenotype-guided WES in selected patients aged ≥17 years with epilepsy and complex neurological manifestations in Southern Kazakhstan and to characterize clinical, therapeutic, and molecular features associated with drug-resistant epilepsy (DRE). Methods: This observational cohort included 78 patients aged ≥17 years with epilepsy and complex neurological manifestations identified through 25 outpatient medical centers. After enrollment, all patients underwent structured HPO-based phenotyping, assessment of antiseizure medication exposure, seizure burden, treatment response, and proband-only WES. Variants were interpreted according to ACMG/AMP guidelines. Exploratory multivariable logistic regression was used to assess factors associated with DRE. Results: P/LP variants were identified in 12/78 patients, corresponding to a diagnostic yield of 15.4%. VUS were detected in 16/78 patients (20.5%). DRE was present in 41 patients (52.6%), all of whom were receiving polytherapy. Carbamazepine was the most frequently used antiseizure medication (52/78, 66.7%), followed by valproic acid (32/78, 41.0%) and levetiracetam (20/78, 25.6%). Patients with DRE had earlier seizure onset, more frequent definite structural MRI abnormalities, and a higher proportion of P/LP variants. In the adjusted model, P/LP variant presence and definite structural MRI abnormality were associated with DRE. Conclusions: Phenotype-guided proband-only WES provided clinically relevant diagnostic information in a real-world epilepsy cohort with complex neurological manifestations in a resource-limited outpatient setting. The observed burden of DRE and polytherapy supports the potential value of integrating therapeutic profiling, neuroimaging, and genomic testing in the etiological evaluation of patients with epilepsy and additional neurological features.