Metabolites

Objective: Visceral adipose tissue is a primary driver of insulin resistance and dysglycemia in type 2 diabetes (T2D), yet its clinical assessment remains challenging. This study aimed to validate neck circumference (NC) as a novel, practical anthropometric biomarker for estimating visceral fat area (VFA) and identifying metabolic risk in a T2D cohort, facilitating its integration into public health and primary care screening strategies. Methods: In a cross-sectional study of 1139 T2D patients, we collected data on NC, biochemical parameters (fasting plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and precisely measured VFA and subcutaneous fat area (SFA) via bioelectrical impedance analysis (Omron HDS-2000). We employed Pearson’s correlation and multivariate logistic regression to analyze the relationship between NC and metabolic indicators. Receiver operating characteristic (ROC) curve analysis was used to establish sex-specific NC cut-off values for predicting abnormal VFA. Results: The cohort comprised 687 (60.3%) males and 452 (39.7%) females. NC demonstrated strong positive correlations with VFA (p < 0.001), as did body mass index (BMI), waist–hip ratio (WHR), and SFA. In males, NC was further positively correlated with key metabolic biomarkers including fasting insulin, Insulin Resistance Index, triglycerides, and creatinine. ROC analysis identified NC > 39.5 cm for males and >35.5 cm for females as the optimal cut-off points for detecting abnormal visceral adiposity, highlighting its diagnostic utility. Conclusions: NC serves as a highly accessible and effective biomarker for visceral adiposity and associated metabolic dysfunction in patients with T2D. The established sex-specific cut-off values provide a simple, non-invasive tool for risk stratification in clinical and public health settings, enabling early intervention and improved management of metabolic disease.

The gut immune microenvironment and the liver engage in intricate information exchange via the gut–liver axis. The disruption of these interactions plays a pivotal role in the formation and exacerbation of pathological damage to the liver. The gut immune microenvironment is not an independent layer of the gut barrier; rather, it permeates and regulates all other barrier functions, serving as the core coordinator. Disruption of the immune microenvironment in the gut–liver axis drives progression across the full disease spectrum—from steatosis to hepatitis, fibrosis, and even liver cancer—through the continuous influx of immune-stimulatory signals that overwhelm the liver’s intrinsic immune regulatory mechanisms. Dysfunction of innate immunity components, amplification of inflammatory factors and key cellular signaling pathways, activation of adaptive immune T cells, and systemic effects mediated by liver-derived inflammatory factors collectively form a disordered immune microenvironment. This damages the intestinal barrier and exacerbates liver disease via the gut–liver axis, leading to further intestinal injury, thus establishing a self-reinforcing vicious cycle. Current therapeutic strategies based on modulating the gut–liver axis microenvironment remain limited, yet studies have demonstrated that suppressing gut immune cells, cytokines, and signaling pathways can help delay liver disease progression. Hopefully, future combined, precise, and cutting-edge gut immunotherapies will provide more effective strategies for liver disease treatment.

Background/Objectives: Insulin-Resistant Normal Weight and Insulin-Sensitive Obesity are atypical cardiometabolic phenotypes whose clinico-biological features, management, and prognosis are a subject of extensive scientific debate. The current study aimed to assess the prevalence of metabolic phenotypes of obesity and to evaluate their association with markers related to diabesity, adipokines profile, and two single nucleotide polymorphisms of CNR1 gene. Methods: We performed a cross-sectional analysis in a random sample of 487 individuals (53.03 ± 13.71 years, 48.3% male) which were classified based on body mass index (</≥25 kg/m²) and insulin resistance (HOMA-IR cut-off value 2.5) as Insulin-Sensitive/Insulin-Resistant Normal Weight (ISNW/IRNW) and Insulin-Sensitive/Insulin-Resistant Obesity (ISO/IRO). Results: The ISO phenotype frequency was 24.2%, with a higher prevalence in the 40–60 years age group (47.0%) and in men (44.9%), while the prevalence of IRNW was 7.0%, predominating in women (61.8%). Participants with IRNW had a more altered glycoregulation profile (fasting and 2 h OGTT blood glucose, prediabetes, and hyperinsulinism), hypercholesterolemia, and adiposity indices (ABSI) than those with ISNW, but comparable to those with IRO. Participants with ISO had a more favorable glycoregulation profile, lipid profile, adipocytokines, and adiposity indices than those with IRO. IRNW had higher odds of being associated with prediabetes (OR 10.75; p < 0.001) than ISNW, while younger age, CUN-BAE, and ABSI were independently associated with both ISO and IRNW phenotypes. Conclusions: The IRNW phenotype should be actively evaluated to intervene on the cardiometabolic risk, while further studies are needed to confirm the sustainability of the favorable cardiometabolic profile of the ISO phenotype.