Metabolic Syndrome and Related Disorders

Metabolic syndrome (MetS) is a multifactorial condition characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of cardiovascular disease and type 2 diabetes mellitus. Genetic variants affecting adipokine signaling, such as polymorphisms in the vaspin gene (SERPINA12), have gained attention due to their potential role in modulating metabolic traits. Among these, the single nucleotide polymorphism rs2236242 (T>A) has shown conflicting associations with MetS across populations. This study presents the first comprehensive meta-analysis investigating the association between rs2236242 polymorphism and MetS susceptibility.

We searched PubMed, Google Scholar, Scopus, and Web of Science for relevant articles published up to 12 December 2025. Data were extracted, and summary estimates of the association between vaspin rs2236242 and MetS were assessed. Odds ratios (ORs) and confidence intervals (CIs) were used to measure the effect. Four eligible case-control studies involving 918 participants from Caucasian, African, and Western Asian populations were included.

Our results demonstrate that the A allele of rs2236242 is significantly associated with a 37% reduced risk of MetS compared to the T allele, with consistent protective effects observed across multiple genetic models (dominant, recessive, homozygous, and heterozygous). These findings align with previous studies suggesting the metabolic benefits of vaspin, including improved insulin sensitivity. Moreover, sensitivity analyses identified the study by Suliga et al. as an outlier, its exclusion reduced heterogeneity to 0% while maintaining the significance of the protective association.

We performed the first meta-analysis on the association of vaspin rs2236242 with MetS and found that the vaspin rs2236242 A allele confers a significant protective effect against MetS.

Psoriasis (PsO) demonstrates frequent co-occurrence with metabolic syndrome (MetS). Nevertheless, the shared genetic architecture underlying both pathological conditions remains incompletely characterized. This investigation sought to examine genetic correlations between PsO and multiple MetS-associated traits, and to identify shared genetic risk loci and genes contributing to their coexistence.

Genome-wide association study data for PsO, MetS, and related traits in European populations were integrated to evaluate genetic associations between traits and to identify shared loci. Bayesian colocalization analysis was applied to determine whether association signals for different traits at the same locus were attributable to a common causal variant. Functional annotation and gene mapping were conducted for shared loci, followed by functional classification and pathway enrichment analyses of pleiotropic gene sets. In addition, summary data-based Mendelian randomization and transcriptome-wide association study analyses were applied to prioritize candidate genes with potential therapeutic relevance.

Significant genetic associations were observed between PsO and five metabolic traits, including body mass index, high-density lipoprotein cholesterol, triglycerides, waist circumference, and type 2 diabetes mellitus, while MetS, as a composite trait, also exhibited a genetic association with PsO. Pleiotropic Analysis under composite null hypothesis (PLACO) analysis revealed a total of 141 shared risk loci, with 22 loci substantiated by Bayesian colocalization analysis findings (PP.H4 ≥ 0.75). Multimarker analysis of genomic annotation analysis identified 195 distinct pleiotropic genes. The pathway enrichment analysis indicated that these genes were predominantly involved in immune and inflammatory pathways, transcriptional and epigenetic regulation, autophagy, and lipid–cholesterol metabolism, indicating that such biological processes may contribute to the shared genetic background of PsO and MetS-related traits. Through integrative evidence from multiple analytical approaches, three candidate therapeutic target genes, namely, KAT8, STX4, and VKORC1, were prioritized.

Shared genetic loci, pleiotropic genes, and core biological pathways between PsO and multiple MetS-related traits were identified, and potential intervention targets were highlighted, providing genetic evidence to support subsequent functional investigations.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is driven by complex immune and inflammatory mechanisms. Visceral adiposity, a key contributor, worsens inflammation, immune dysregulation, and insulin resistance.

This study examines correlations between inflammatory genes, insulin resistance markers, and inflammatory markers across visceral adiposity levels in patients with MASLD.

This cross-sectional study included 102 patients with MASLD. Assessments included body mass index, visceral adiposity index (VAI), a body shape index (ABSI), inflammatory markers, gene expression from peripheral white blood cells, and serologic inflammatory proteins. We calculated insulin resistance markers, such as homeostasis model assessment–insulin resistance index (HOMA-IR), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride-glucose (TyG) index, and neutrophil-to-HDL ratio (NHR). Pearson correlation coefficients evaluated parameter associations between low and high VAI and ABSI groups.

The higher VAI group presented with some elevated markers, such as HOMA-IR (5.21 ± 3.42 vs. 4.34 ± 4.62), TG/HDL-C (4.08 ± 1.97 vs. 2.20 ± 1.07), TyG (9.03 ± 0.48 vs. 8.70 ± 0.51), and NHR (1.86 ± 0.75 vs. 1.45 ± 0.64) compared with the low VAI group, indicating potentially greater insulin resistance and systemic inflammation. Monocyte chemoattractant protein-1 and interleukin-6 genes were strongly correlated in the low VAI group (R = 0.94, P < 0.001) but more weakly correlated in the high VAI group (R = 0.63, P < 0.001).

These findings highlight differential immune changes across visceral adiposity levels in MASLD, supporting the need for tailored interventions based on adiposity profiles.

Visceral obesity is considered an important risk factor for hypertension. However, there is little research on visceral obesity and hypertension in patients with diabetes or prediabetes. Body roundness index (BRI) serves as a proxy for visceral adiposity. Therefore, the purpose of this study is to investigate the relationship between BRI and hypertension and blood pressure in diabetes (DM) or prediabetes (preDM).

This study includes data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, including 5368 participants with DM and preDM. Weighted multiple regression, restricted cubic spline (RCS), and subgroup analysis were used to evaluate the correlation between BRI and hypertension risk as well as blood pressure.

This study included a total of 1565 DM subjects and 3803 preDM participants. The prevalence of hypertension in the two groups was 67.80% and 42.28%, respectively. After adjusting for potential confounding factors, BRI was significantly positively correlated with the risk of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in both DM and preDM. In the fully adjusted model, an increase in BRI was positively associated with the risk of hypertension in both DM and preDM participants (DM OR: 1.25, 95% CI: 1.16–1.34, P < 0.0001; preDM OR: 1.20, 95% CI: 1.14–1.26, P < 0.0001). Further RCS analysis revealed a significant nonlinear relationship between BRI and hypertension and DBP in DM and preDM, while there was a linear positive correlation with SBP. Interaction analysis indicated that in male preDM, BRI was associated with a higher risk of hypertension (male OR: 1.28, 95% CI: 1.19–1.39, female OR: 1.12, 95% CI: 1.07–1.17, P for interaction <0.01). Additionally, in preDM under the age of 60, BRI showed a stronger positive correlation with SBP and DBP (OR: 1.23, 95% CI: 0.94–1.52, P < 0.0001; OR: 0.68, 95% CI: 0.45–0.90, P < 0.0001). However, these findings were not observed in DM.

In diabetes and prediabetes, BRI exhibits a significant positive correlation with the risk of hypertension, as well as with systolic and diastolic blood pressure. Based on these findings, BRI may serve as a biomarker for managing the progression of hypertension in patients with DM and preDM.

In patients with type 2 diabetes (T2DM), glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control and have been shown to enhance stress regulation, potentially attenuating the cumulative impact of chronic stress. Despite these links, few studies have examined allostatic load in patients with T2DM treated with GLP-1s.

To compare allostatic load among patients with T2DM treated with GLP-1s and three comparison groups: individuals without T2DM, individuals with T2DM not receiving medication treatment, and individuals with T2DM treated with non-GLP-1 medications.

We analyzed data from 16,830 adults in the 2007–2018 National Health and Nutrition Examination Survey. Medication status was based on self-reported prescription use within the past month. Allostatic load was calculated primarily using a 13 biomarker index spanning metabolic, autonomic, and immune function and secondarily using a modified score that excluded HbA1c and insulin resistance. General linear regression was used to assess associations, adjusting for sociodemographics, comorbidities, and health behaviors.

Participants with T2DM treated with GLP-1s had higher allostatic load than those without T2DM (β = 1.57, 95% CI: 0.88, 2.25) but did not differ from participants with T2DM who were untreated or treated with non-GLP-1s. After excluding HbA1c and insulin resistance from the score, allostatic load in the GLP-1s-treated group was comparable across all comparison groups.

GLP-1 treatment was not associated with lower allostatic load compared with other treatment regimens in patients with T2DM. Longitudinal studies with neuroendocrine measures are needed to better characterize its effects on stress regulation.