Abstract Objectives Type 2 diabetes mellitus (T2DM) is linked to impaired natural killer (NK) cell function and altered sex hormone homeostasis. We examined the associations of HbA 1c , sex hormones and NK-cell subsets with peripheral blood mononuclear cell (PBMC) cytotoxicity. Methods In this cross-sectional study, 58 patients with T2DM and 62 metabolically healthy controls were enrolled. PBMC cytotoxicity (specific lysis of K-562-GFP target cells, an NK cell-associated readout) was measured by flow cytometry. Serum estradiol, testosterone and HbA 1c were measured, and NK-cell subsets were quantified by flow cytometry. In an exploratory sub-cohort of 16 patients undergoing bariatric surgery, omental adipose tissue (OAT)-derived immune cells were compared with paired PBMCs. Results There was a reduction in PBMC cytotoxicity for men with T2DM compared to control men and for women compared to men with T2DM. Multiple regression analysis showed that the cortisol level and PBMC cytotoxicity were inversely correlated (adjusted R 2 =0.218), while the testosterone level and percentage of CD56 + CD16 + NK-cells were positively correlated (adjusted R2=0.218). The OAT-derived cells proved to be more cytotoxic than matched PBMCs (p=0.0005). Conclusions These are theory generating associations. The cross-sectional design and limited number of children in the OAT sub-cohort and the lack of surgical control group in the non-diabetic population limit the ability to make causal inferences and need to be confirmed in future prospective studies.
Abstract Objectives Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic, reproductive, and psychological disturbances. Alarin, a neuropeptide of the galanin family, has been implicated in energy metabolism and insulin resistance, and experimental studies suggest a role in mood regulation. However, its association with psychiatric features in PCOS remains unclear. This study aimed to evaluate circulating alarin levels in women with PCOS and their relationship with depression, anxiety, and metabolic-hormonal parameters. Methods This case-control study included 180 women divided into four groups: PCOS with depression, PCOS without depression, depression without PCOS, and healthy controls (45 participants each). Clinical, biochemical, and hormonal assessments were performed, including measurement of serum alarin levels. Depression and anxiety were assessed using validated Hamilton rating scales. Results Serum alarin levels were significantly higher in women with PCOS, irrespective of comorbid depression, compared with healthy controls and women with depression without PCOS. Women with depression alone showed alarin levels comparable to controls. Factorial analysis showed significant effects of PCOS status and depression status, with no significant PCOS × depression interaction (p=0.37). Serum alarin correlated positively with fasting insulin, HOMA-IR, and luteinizing hormone, but not with depression or anxiety severity. Multivariate analysis identified luteinizing hormone and PCOS status as independent predictors of serum alarin levels. Receiver operating characteristic analysis demonstrated excellent discriminative performance for PCOS. Conclusions Circulating alarin is closely associated with the metabolic and reproductive features of PCOS rather than psychiatric symptom severity, indicating a stronger link to endocrine-metabolic dysregulation.
Abstract Objectives Visceral obesity is closely linked to insulin resistance and cardiometabolic risk. Epicardial adipose tissue, commonly assessed by epicardial fat thickness (EFT), is a clinically relevant fat depot associated with early cardiac remodelling. Sclerostin, a bone-derived protein, may play a role in crosstalk between the skeleton and adipose tissue. However, its relationship with insulin resistance and cardiac visceral fat remains unclear. This study aimed to evaluate serum sclerostin levels and their association with insulin resistance and EFT in obese women. Methods This case-control study included 90 women (55 obese and 35 age-matched controls). Participants underwent anthropometric and metabolic assessment, including serum sclerostin measurement. Insulin resistance was evaluated using HOMA-IR, and EFT was assessed by echocardiography. Correlation, ROC, and regression analyses were performed. Results Serum sclerostin levels were significantly higher in obese women than in controls (p<0.001). Sclerostin was positively correlated with fasting insulin, HOMA-IR, triglycerides, and EFT. Levels were higher in insulin-resistant obese participants than in metabolically healthier obese individuals. ROC analysis showed good discriminative ability for insulin resistance (AUC=0.89) and moderate accuracy for identifying increased EFT (AUC=0.80). In multivariate analysis, BMI, but not sclerostin, remained an independent predictor of increased EFT. Conclusions Serum sclerostin is elevated in obese women and is associated with insulin resistance and adverse metabolic profiles. Although not independently associated with epicardial fat thickness, it reflects metabolic dysfunction related to visceral adiposity and may serve as an indicator of metabolically unhealthy obesity within this cohort.
Abstract Objectives Xenin regulates appetite, motility, and metabolic homeostasis. As the link between smoking and xenin has not yet been sufficiently investigated, this study compared serum levels between smokers and non-smokers and evaluated their associations with metabolic, hematological, and tobacco-related parameters. Methods Utilizing a cross-sectional case-control framework, the present study evaluated a group of 128 subjects, comprising 66 smokers and 62 non-smokers. Serum xenin levels and clinical, metabolic, lipid, and hematological parameters were compared between groups. Subgroup analyses were performed according to sex, body mass index (BMI), and HOMA-IR categories. Correlation analyses were conducted to evaluate the associations of xenin with smoking exposure, nicotine dependence, and laboratory variables. Results Circulating xenin concentrations exhibited a significant elevation in the smoking group relative to non-smokers (p<0.001), and this difference persisted across the normal-weight (p=0.001), overweight (p=0.002), and obese (p<0.001) BMI categories, as well as in the HOMA-IR <2.5 (p=0.043) and HOMA-IR ≥2.5 (p<0.001) subgroups. In addition, xenin levels were positively correlated with pack-years, Fagerström score, HOMA-IR, and glucose (all p<0.05). Although xenin levels tended to increase with greater smoking exposure, the overall difference among smoking exposure groups was not statistically significant (p=0.151). Conclusions Serum xenin levels were significantly higher in smokers than in non-smokers, and this difference remained significant across BMI and HOMA-IR subgroups. These findings suggest that circulating xenin may be associated with smoking-related metabolic and neuroendocrine alterations and may have potential as a candidate biomarker. Further prospective studies are needed to validate its clinical relevance.
Abstract Objectives To evaluate biochemical, hormonal, genetic, and mitochondrial alterations associated with cardiovascular risk in SCH, emphasizing the interplay between NT-proBNP, succinate dehydrogenase (SDH) complex activity, and thyroid-stimulating hormone receptor (TSHR) gene expression. Methods A case–control study was conducted involving SCH patients and age-matched euthyroid controls. Serum thyroid profiles, NT-proBNP, and SDH complex activity were quantified by standard assays, and TSHR gene expression was measured using RT-PCR. Receiver operating characteristic (ROC) analyses assessed diagnostic performance, and multiple linear regression identified independent predictors of TSHR expression. Results Compared with controls, SCH cases showed significantly higher TSH and NT-proBNP levels, reduced SDH complex activity, and upregulated TSHR gene expression (p<0.05). ROC analysis demonstrated excellent diagnostic accuracy for NT-proBNP, SDHA, and TSHR expression. After adjustment for confounders, SDH complex activity remained the only independent predictor of TSHR expression, whereas NT-proBNP lost independent significance, suggesting an indirect or interaction-mediated effect. Conclusions SDHA serves as a robust independent predictor of cardiovascular risk in SCH, highlighting mitochondrial dysfunction in thyroid receptor regulation. NT-proBNP showed predictive potential but not independent significance, indicating secondary modulation by hormonal or metabolic factors. Larger longitudinal studies are warranted for validation.
