Hepatic steatosis (HS) represents one of the most frequent metabolic complications of pediatric obesity and is closely linked with insulin resistance (IR). Although the homeostatic model assessment for insulin resistance (HOMA-IR) is widely used, lipid-derived indices such as the triglyceride-glucose (TyG) index and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio have recently emerged as simple IR surrogates. Data comparing these indices with HS severity in children remain limited. This single-center retrospective study included 462 children aged 6-18years with overweight or obesity who were evaluated between October 2023 and December 2024. Anthropometry, biochemical data, and ultrasonographic HS grading were obtained from medical records. HOMA-IR, TyG, and TG/HDL-C indices were calculated, and their associations with HS presence and severity were analyzed using correlation and multivariable regression models. HS was identified in 53.5 % of participants (grade 1: 29.9 %, grade 2: 16.6 %, grade 3: 6.0 %). Children with HS demonstrated significantly higher HOMA-IR, TyG index, and TG/HDL-C ratio compared with those without HS (all p<0.001). HOMA-IR increased progressively with HS grade (p<0.05), whereas TyG and TG/HDL-C did not display a significant gradient. Logistic regression confirmed that HOMA-IR was independently associated with HS severity (β=0.261; 95 % CI: 0.030-0.078; p<0.001), while TyG and TG/HDL-C were not. ALT levels rose significantly with HS grade, whereas AST showed no severity-related pattern. HOMA-IR remains the strongest metabolic predictor of hepatic steatosis severity in pediatric obesity. Although TyG and TG/HDL-C reliably differentiate HS presence, they do not independently estimate HS progression. Lipid-derived markers may support non-insulin-based screening; however, HOMA-IR should be prioritized when stratifying steatosisrisk.

Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events in type 2 diabetes. Although body mass index does not seem to modify these effects, whether insulin resistance influences treatment efficacy remains unclear. This post hoc analysis of the LAMP trial (Liraglutide in Acute Minor Ischemic Stroke or High-Risk Transient Ischemic Attack Patients With Type 2 Diabetes Mellitus; a multicenter, open-label, randomized controlled trial conducted at 27 hospitals in China between June 25, 2019, and December 27, 2023) included patients with minor ischemic stroke or high-risk transient ischemic attack and type 2 diabetes. Participants were randomized (1:1) to liraglutide plus standard therapy or standard therapy alone. IR was assessed using the homeostasis model assessment of IR, with a cutoff of 2.5 based on prior studies in Asian populations. Treatment-by-IR interactions were evaluated using Cox models. Absolute risk reduction was calculated as the difference in event rates between groups and was based on crude estimates. Among 636 enrolled patients, 510 were included in this analysis (mean age, 65 years; 64.7% male; follow-up, 3 months). A significant interaction between treatment and insulin resistance was observed for both stroke recurrence and composite vascular events (P for interaction=0.02 for both). Among patients with homeostasis model assessment of IR ≥2.5, liraglutide reduced stroke recurrence (5.8% versus 18.1%; absolute risk reduction, 12.3% [95% CI, 5.6%-19.0%]; number needed to treat=8) and vascular events (5.8% versus 19.2%; absolute risk reduction, 13.4% [95% CI, 6.6%-20.2%]; number needed to treat=8). No significant benefit was observed in those with homeostasis model assessment of IR <2.5. IR may be an important determinant of the therapeutic efficacy of liraglutide in patients with acute minor ischemic stroke or high-risk transient ischemic attack and type 2 diabetes. IR-based stratification may help optimize the use of glucagon-like peptide-1 receptor agonists in secondary stroke prevention and guide personalized vascular risk management. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03948347.

Melatonin supplementation improves insulin resistance markers but not fasting glucose: a systematic review and meta-analysis of randomized controlled trials.

Insulin resistance is a chronic, low-grade inflammatory condition and a central pathological feature of obesity and related conditions, including metabolic syndrome (MetS). Oxidative stress, inflammatory pathways, and dysregulation of adipokine secretion may contribute to its development. This study aimed to clarify these biological relationships using principal component analysis (PCA) in individuals with MetS. The study involved 190 adults diagnosed with MetS. Serum concentrations of metabolic and inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]), oxidative stress indicators (glutathione peroxidase [GPx], superoxide dismutase [SOD], total antioxidant capacity [TAC], and total oxidant status [TOS]), and adipokines (omentin-1, adiponectin, visfatin, and leptin) were measured. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. PCA was conducted to investigate the associations between clusters of these biomarkers and HOMA-IR. Compared to individuals with HOMA-IR ≤ 2.5, those with HOMA-IR > 2.5 had significantly elevated serum triglycerides and TNF-α concentrations, as well as significantly lower levels of adiponectin, omentin-1, and TAC. PCA extracted 4 components explaining 59.45% of the total variance: lipid profile-related factor, oxidative stress-related factor, inflammatory-related factor, and adipokine profile factor. Of all 4 principal components, the inflammatory-related factor (i.e., hs-CRP and TNF-α) and the adipokine profile factor (i.e., leptin, adiponectin, and omentin-1) were independently associated with HOMA-IR > 2.5. Adipokine dysregulation, along with increased inflammation and oxidative stress, was associated with insulin resistance in MetS. PCA-derived biomarker clusters provide a mechanistic and integrative comprehension of metabolic risk stratification and may enable risk assessment and therapeutic strategies in the future.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder among women of reproductive age with significant metabolic impairments. Time-restricted eating (TRE) has emerged as a promising dietary strategy for improving metabolic health. Although both early time-restricted eating (eTRE) and mid-day time-restricted eating (mTRE) have shown beneficial metabolic effects, their comparative efficacy in women with PCOS remains unclear. This study aimed to directly compare the effects of eTRE and mTRE on glycemic control, lipid profiles, and anthropometric outcomes in women with PCOS. In this 6-week randomized controlled trial, 75 women with PCOS were allocated to one of three groups: eTRE (8:00 AM-6:00 PM), mTRE (11:00 AM-9:00 PM), or a control group with ad libitum eating. The primary outcome was fasting insulin level. Secondary outcomes included FBS, insulin resistance indices, lipid profile (total cholesterol (TC), LDL-C, HDL-C, and TG), body weight, BMI, waist circumference (WC), and dietary intake. Metabolic and anthropometric variables were assessed at baseline and post-intervention, while dietary intake was evaluated at baseline, mid-intervention, and study completion. Both eTRE and mTRE significantly reduced FBS, fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), body weight, and WC compared with the control group (P < 0.05). Additionally, eTRE significantly improved TC (P < 0.001) and LDL-C levels (P = 0.01), whereas similar changes were not observed in the mTRE group. TRE, particularly eTRE, appears to be an effective dietary intervention for women with PCOS, offering significant benefits for glycemic control, metabolic health, and weight management. IRCT20221122056575N1.

The homeostatic model assessment for insulin resistance (HOMA-IR) is one of the most commonly applied surrogate markers for the measurement of insulin resistance; however, the use of this metric does require sex-specific, age-specific, and body mass index (BMI)-specific reference ranges due to variations among populations and there is a lack of data in countries like Iraq on such reference ranges. The purpose of this investigation was to develop sex-, age-, and BMI-specific reference ranges for HOMA-IR in apparently healthy Iraqi adults aged 18 to 60 years. There were 2,160 participants enrolled in the study who were equally divided into sex-specific groups and age groups (18-30, 31-45, and 46-60 years) and BMI categories (normal weight, overweight, and obesity). In addition to measuring fasting glucose and insulin levels, the HOMA-IR was calculated. Reference ranges, which included the 2.5th and 97.5th percentiles of HOMA-IR, were developed using non-parametric statistical methods based on CLSI EP28-A3c guidelines. The results demonstrated that HOMA-IR values increased as both age and BMI increased (p < 0.001). Also, males consistently had higher HOMA-IR values compared to females within similar subgroups. All between-group comparisons were statistically significant. It is important to use sex-, age-, and BMI-specific reference intervals when interpreting HOMA-IR to avoid misclassifying subjects in clinical and epidemiologic studies. This investigation represents the first large-scale study to identify such reference intervals in Iraq and adds relevant regional data to the global research on the prevalence of insulin resistance.

Ginger has shown promising effects on metabolism in preclinical and clinical studies. This updated and comprehensive meta-analysis aimed to investigate the effects of ginger on the cardiometabolic profile of patients with type 2 diabetes. Scopus, PubMed, the Cochrane Library, and Web of Science were searched from the inception to July 2, 2025, to find randomized controlled trials that compared the effects of ginger with placebo on glycemic indexes, blood pressure, and lipid profile among those with type 2 diabetes. A random-effects model (DerSimonian-Laird) was employed to pool data because of high heterogeneity. In total, 13 articles were included in this meta-analysis. Ginger supplementation was associated with a statistically significant reduction in fasting blood sugar (FBS) (MD -16.27 mg/dl, 95% CI (-25.75, -6.80), I2 = 86.39%), hemoglobin A1c (HbA1c) (MD -0.41%, 95% CI (-0.63, -0.20), I2 = 92.09%) systolic blood pressure (MD -1.62, 95% CI (-3.01, -0.24), I2 = 6.09%), and triglyceride level (MD -17.10 mg/dL, 95% CI (-31.13, -3.07), I2 = 81.61%); however, the magnitude of these effects was of limited clinical importance. A statistically significant increase in high-density lipoprotein cholesterol (HDL-C) level (MD 2.13 mg/dL, 95% CI (0.44, 3.82), I2 = 85.72%) was also observed. However, treatment with ginger did not significantly change homeostasis model assessment for insulin resistance (HOMAIR), diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI). This meta-analysis indicated that ginger may probably improve the metabolic indices of patients with type 2 diabetes.

Childhood obesity has been strongly associated with insulin resistance and dysglycaemia. We aimed to evaluate fasting biomarkers and glycated haemoglobin (HbA1c) for identifying children at risk and guiding the need for oral glucose tolerance testing (OGTT). This single-centre study included 475 consecutive children aged 5-18 years with excess weight who underwent OGTT. Insulin resistance and dysglycaemia were defined based on OGTT-derived indices. Fasting glucose (FG), fasting insulin (FI), homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β), and HbA1c were evaluated. Receiver operating characteristic (ROC) analysis was used to determine optimal cut-offs for predicting dysglycaemia. The cohort comprised 281 girls (59.2%) and 194 boys, with a median age of 13.8 years. Insulin resistance was present in 81.5% (387/475) and dysglycaemia in 18.9% (90/475). FG above the 90th percentile, FI and HOMA-IR above the 97.5th percentile, and HbA1c ≥ 39 mmol/mol (5.7%) were significantly associated with dysglycaemia (p < 0.05). ROC analysis for the entire cohort identified FG 5.27 mmol/L, HbA1c 39 mmol/mol, and HOMA-IR 4.88 as significant cut-offs (all p < 0.001). Fasting biomarkers and HbA1c identified children with excess weight at risk of dysglycaemia, providing practical thresholds to guide the need for OGTT.

There is evidence linking activation of aldosterone activity with insulin resistance and metabolic risk factors. We hypothesized that finerenone, a nonsteroidal mineralocorticoid receptor antagonist, might improve insulin resistance in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In a single-center retrospective study including 45 patients with T2D and CKD treated with finerenone for 12 months between June 2023 and June 2025, we assessed insulin resistance using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and triglyceride-glucose (TYG) index along with metabolic and renal parameters measured at baseline, month-6, and month-12. In these patients (n = 45; mean age 52.2 ± 13.9 years; 64.4% male; disease duration >10 years in 48.9%; mean HbA1c 9.2 ± 2.5%; 60.0% treated with SGLT2i; 33.3% on GLP1RA), 12-month treatment with finerenone was associated with improvement in HOMA-IR (median [interquartile range]: baseline: 34.40 [12.84, 71.50], month-6: 25.22 [13.54, 78.19], month-12: 19.44 [9.51, 45.75] [P = 0.038, Friedman test]). TYG index (baseline: 9.49 [8.86, 10.29] month-6: 9.04 [8.54, 9.71], and month-12: 8.93 [8.44, 9.62] mg/dL [P < 0.007 Friedman tset]); urinary albumin: creatinine ratio (baseline: 377.39 [127.80, 1327.29], month-6: 342.96 [87.58, 1442.12], month-12: 249.52 [68.04, 1198.03] mg/g [p = 0.05, Friedman test]) and estimated glomerular filtration rate (baseline: 112.01 [85.87, 120.00], month-6: 103.92 [75.25, 120.00], and month-12120.00 [80.46, 120.00] mL/min/1.73 m2 [P = 0.002 Feirdman test]). There was no treatment discontinuations due to hyperkalemia. In real-world practice, 12-month treatment with finerenone was associated with reduced insulin resistance and improved kidney function in patients with T2D and CKD and a manageable safety profile.

Type 2 diabetes mellitus is a complex metabolic disorder with rising prevalence in Nigeria. APOL1 and NOTCH2 have been implicated in glucose metabolism, adiposity, and diabetic complications, necessitating comparison of APOL1 and NOTCH2 gene expression in patients with T2DM and healthy controls. A case-control study was conducted among 50 participants attending Babcock University Teaching Hospital, Nigeria. Participants were consecutively recruited based on eligibility and sample availability during the study period. Sociodemographic, anthropometric, and clinical data were collected. Biochemical analyses included fasting plasma glucose, lipid profile, urea, creatinine, glycated haemoglobin, serum insulin, and insulin resistance estimated using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Gene expression of APOL1 and NOTCH2 in peripheral blood mononuclear cells was quantified using real-time reverse transcription quantitative PCR. Group comparisons and correlation analyses were performed using parametric or non-parametric statistical methods, including Pearson's or Spearman's correlation tests, depending on data distribution. Participants with T2DM demonstrated significantly higher fasting glucose, HbA1c, triglycerides, urea, and HOMA-IR compared with controls (p < 0.05). Cases exhibited significantly higher fasting glucose, HbA1c, triglycerides, urea, and HOMA-IR, indicating poor glycaemic control and increased insulin resistance. APOL1 expression was significantly lower in T2DM cases compared with controls (p < 0.05), whereas NOTCH2 expression did not differ significantly between groups. APOL1 expression correlated positively with adiposity measures but showed significant inverse associations with fasting glucose, HbA1c, and urea. NOTCH2 expression was negatively associated with age and fasting glucose and positively correlated with hip circumference. A moderate positive correlation was observed between APOL1 and NOTCH2 expression. These findings highlight the importance of integrating molecular markers with clinical and biochemical data to improve understanding of T2DM in African populations.

This trial evaluated the combined effect of yoga and camelina sativa powder (CSP) on glycemic indices, inflammatory and oxidative stress parameters in women with type 2 diabetes mellitus (T2DM). In this trial, 80 patients with T2DM were randomly allocated into four groups: group 1 (placebo), group 2 (receiving CSP), group 3 (doing yoga), and group 4 (receiving CSP and doing yoga) for 8 weeks. Glycemic indices, inflammatory and oxidative stress parameters were assessed pre-and post-intervention. CSP plus yoga treatment significantly increased the McAuley-index and Quick-index compared to the placebo group (P = 0.021 and P < 0.001, respectively). A significant decrease in the glycemic exposure (GE) index (P = 0.010), fasting blood sugar (FBS) (P = 0.003), hemoglobin A1c (P = 0.013), insulin (P = 0.002), and homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001) was found in the CSP plus yoga group compared to the placebo after adjustment for confounders. Serum superoxide dismutase level significantly increased in camelina, yoga, and both CSP plus yoga groups compared to the placebo group (P < 0.001, P = 0.019, and P = 0.005, respectively). Serum catalase levels increased significantly in CSP plus yoga group compared to the placebo following 8 weeks (P = 0.022). Malondialdehyde concentration declined significantly in yoga and CSP plus yoga groups compared to placebo (P = 0.017 and P < 0.001, respectively). Serum tumor necrosis factor-α (TNF-α) level significantly decreased in CSP, yoga, and combined CSP plus yoga groups compared with the placebo group (P < 0.001, P = 0.033, and P < 0.001, respectively). We found a favorable effect of co-treatment of CSP and yoga for 8 weeks in women with T2DM on some glycemic indices, oxidative stress, and inflammatory parameters. The combined effect of yoga and camelina sativa powder on glycemic indices, inflammation, and oxidative stress. PPAR-γ: peroxisome proliferator-activated receptor gamma, NF-kB: nuclear factor kappa B, GLP: glucagon-like peptide, PYY: peptide YY, SCFA: short chain fatty acids, ROS: reactive oxygen species, LPS: lipopolysaccharides, HPA: hypothalamic-pituitary-adrenal axis.

The coexistence of obesity and insulin resistance is associated with elevated plasma amino acid concentrations. However, it remains unclear whether adiposity or insulin resistance is the stronger determinant of plasma amino acid dysregulation in this setting. Twenty-two adults (10 women, 12 men) spanning a broad range of body mass index (BMI) and insulin resistance underwent a 75-g oral glucose tolerance test (OGTT) after an overnight fast. Plasma glucose, insulin, and amino acid concentrations were measured serially, and insulin resistance/sensitivity was estimated from OGTT-derived glucose and insulin responses, using the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (Matsuda-ISI). Principal component analysis (PCA) of fasting plasma amino acid concentrations showed no clear separation by obesity or insulin resistance classifications. In contrast, PCA of OGTT-stimulated plasma amino acid concentrations revealed clearer clustering by BMI, fat mass, and waist circumference, whereas separation by HOMA-IR and Matsuda-ISI was less distinct. Importantly, regression analyses showed that BMI, fat mass, and waist circumference were significant predictors of OGTT-stimulated, but not fasting, amino acid responses, with waist circumference accounting for the greatest proportion of the variance in branched-chain amino acid responses during the OGTT (R 2 = 0.54). In conclusion, measures of adiposity, particularly total fat mass and waist circumference, accounted for a greater proportion of the variance in plasma amino acid responses under physiologically stimulated conditions than indices of insulin resistance. These findings support the view that plasma amino acid concentrations reflect adiposity-related metabolic alterations more strongly than insulin resistance.

Periodontitis is increasingly linked to systemic conditions such as diabetes, yet the underlying mechanisms remain unclear. This study aimed to determine whether gut microbiota mediates the impact of periodontitis on glucose homeostasis. Germ-free (GF) mice were obtained and maintained in sterile isolators (GemPharmatech, China) and colonized with microbiota derived from donor mice with ligature-induced periodontitis (GF-LIG) or healthy controls (GF-CON). Donor faecal samples were collected from donor mice with ligature-induced periodontitis or healthy controls. Fasting blood glucose (FBG), serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), as well as glucose tolerance, were evaluated. Correlation analyses were performed to explore associations between microbial composition, short-chain fatty acids (SCFAs), and inflammatory markers. SCFA-producing bacteria were supplemented to assess their potential protective effects. Compared with GF-CON mice, GF-LIG mice exhibited significantly higher FBG, serum insulin, HOMA-IR, HOMA-β, and impaired glucose tolerance. The SCFA-producing genus Lachnospirace-ae_NK4A136_group was negatively associated with FBG, HOMA-β, and serum levels of interleukin (IL)-1β, IL-17A, and tumor necrosis factor (TNF)-α. Moreover, serum levels of IL-1β, IL-17A, and TNF-α were positively correlated with HbA1c and HOMA-β. Notably, supplementation with SCFA-producing bacteria significantly reduced FBG and HbA1c levels in periodontitis-affected mice. These findings suggest that gut microbiota mediates the impact of periodontitis on glucose homeostasis, potentially through SCFAs depletion and inflammation. Restoration of SCFA-producing bacteria may represent a promising microbiota-targeted strategy for mitigating metabolic disturbances associated with periodontitis.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and chronic low-grade inflammation. Pro-inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), contribute to impaired insulin signaling and metabolic dysfunction. Vitamin D possesses immunomodulatory properties and may influence inflammatory pathways associated with insulin resistance. This study aimed to evaluate the association between serum vitamin D levels, TNF-α and IL-6 expression, and glycemic control among insulin-resistant patients with T2DM. A hospital-based case-control study was conducted between September 2025 and February 2026 among 556 participants, including 426 insulin-resistant patients with T2DM and 130 age- and sex-matched healthy controls. Fasting blood samples were analyzed for serum vitamin D, TNF-α, IL-6, fasting blood glucose, insulin, and HbA1c. Insulin resistance was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Serum cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA), while adipose tissue TNF-α and IL-6 gene expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation and multivariable regression analyses were performed to examine associations between vitamin D status, inflammatory markers, insulin resistance, and glycemic indices. Serum vitamin D levels were significantly lower among T2DM patients than controls (17.9 ± 6.8 ng/mL vs. 31.4 ± 7.6 ng/mL, p < 0.001). Conversely, serum TNF-α (18.4 ± 5.2 pg/mL vs. 9.8 ± 3.1 pg/mL, p < 0.001) and IL-6 (12.6 ± 4.7 pg/mL vs. 5.3 ± 2.0 pg/mL, p < 0.001) were significantly elevated in T2DM patients. Adipose tissue analysis demonstrated a 2.8-fold increase in TNF-α expression and a 3.2-fold increase in IL-6 expression among cases compared with controls (p < 0.001). Vitamin D levels were inversely correlated with TNF-α (r = - 0.42), IL-6 (r = - 0.38), HbA1c (r = - 0.35), and HOMA-IR (r = - 0.39) (all p < 0.001). Multivariable regression analysis demonstrated that vitamin D remained an independent negative predictor of TNF-α and IL-6 expression after adjustment for potential confounding variables. Vitamin D deficiency was significantly associated with increased TNF-α and IL-6 expression, greater insulin resistance, and poorer glycemic control among patients with T2DM. These findings support a potential role of vitamin D in metabolic inflammation; however, prospective studies and randomized controlled trials are needed to determine whether improving vitamin D status can favorably influence inflammatory and metabolic outcomes in T2DM.

Background and objectives: numerous studies have shown that selenium has a positive role in the regulation of glucolipid metabolism. However, the effects of selenium supplementation on cardiovascular risk factors remain inconsistent. This study aimed to evaluate the impact of dietary selenium on glycolipid metabolic parameters, inflammatory factors, and oxidative stress levels in individuals with metabolic diseases. Methods and study design: a comprehensive search was conducted up to August 30, 2023, across PubMed, Web of Science, Embase, and Cochrane databases. We included adult randomized controlled trials comparing selenium supplements to placebos in patients with metabolic diseases, focusing on cardiovascular risk factors. We included 11 publications with a total of 656 patients. Results: our analysis showed that dietary selenium significantly reduced HOMA-β (Homeostasis Model Assessment-Beta; p < 0.0001), triglycerides (p = 0.02), high-sensitivity C-reactive protein (p < 0.00001), and plasma malondialdehyde (p < 0.00001), while increasing total antioxidant capacity (p = 0.04). However, selenium had no significant effect on fasting plasma glucose, insulin levels, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, nitric oxide, plasma glutathione, weight change, and body mass index change (all p > 0.05). Conclusions: in conclusion, dietary selenium may improve insulin resistance, triglycerides, inflammation, and oxidative stress in individuals with metabolic diseases, but does not affect other aspects of glucose and lipid metabolism.

Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spectrum in hypertensive adults. We evaluated ten IR indices, three insulin-based [homeostasis model assessment of insulin resistance (HOMA-IR), McAuley index, and quantitative insulin sensitivity check index (QUICKI)] and seven non-insulin-based [triglyceride-glucose index (TyG), stress hyperglycemia ratio (SHR), cardiometabolic index (CMI), atherogenic index of plasma (AIP), estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR), and lipid accumulation product (LAP)], for all-cause mortality (ACM) and cardiovascular mortality (CVM) by glycemic status. This prospective cohort study included 7,548 hypertensive adults from NHANES 1999-2018, classified as normoglycemia (n = 1,869), prediabetes (n = 3,389), and diabetes (n = 2,290). Mortality data were collected through December 31, 2019. Associations were analyzed using Cox models with three levels of adjustment. Dose-response relationships were modeled with restricted cubic splines. Over a mean follow-up of 8.7 ± 5.3 years, 1,752 ACM events (23.2%) and 499 CVM events (6.6%) occurred. In fully adjusted models, HOMA-IR independently predicted ACM (per-unit HR 1.017; Q4 HR 1.165) and CVM (per-unit HR 1.012). eGDR showed the strongest overall associations: ACM: per-unit HR 0.807; Q4 HR 0.559; CVM: per-unit HR 0.774; Q4 HR 0.538. TyG predicted ACM (per-unit HR 1.158; Q4 HR 1.233) and CVM per-unit (HR 1.160). In glycemic-stratified analyses, HOMA-IR was the only index with per-unit ACM significance across all three strata (normoglycemia: HR 1.085; prediabetes: HR 1.039; diabetes: HR 1.012). eGDR showed per-unit and Q4 ACM significance in prediabetes and diabetes, and demonstrated significant quartile-level protection for CVM in both prediabetes (Q4 HR 0.465) and diabetes (Q4 HR 0.463), whereas per-unit associations with CVM were observed only in diabetes. TyG was significantly associated with ACM in diabetes (per-unit HR 1.147; Q4 HR 1.337) and with CVM in diabetes (Q4 HR 1.595). In hypertensive adults, HOMA-IR was the only fasting-insulin-based index independently associated with ACM across all three glycemic strata. eGDR demonstrated the most consistent non-insulin-based associations with ACM and CVM, particularly in prediabetes and diabetes. TyG provided additional prognostic value for ACM and CVM, particularly in patients with diabetes. These findings support selecting IR indices based on glycemic phenotype and data availability.

Polycystic ovary syndrome (PCOS) is a complex metabolic disorder characterized by altered peptide signaling that may contribute to reproductive dysfunction, insulin resistance, and metabolic dysregulation. This case-control study investigated serum phoenixin (PNX) isoforms, phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20), in women with PCOS to evaluate their associations with biochemical and hormonal markers, including anti-Müllerian hormone (AMH), and assess their diagnostic utility. Serum PNX-14 and PNX-20 levels were measured in 90 women with PCOS and 60 age-matched healthy controls. Demographic, metabolic, and hormonal parameters were compared between the groups. Statistical analyses included receiver operating characteristic (ROC) analysis, logistic regression, correlation analysis, principal component analysis (PCA)-based clustering, mediation analysis, and exploratory Random Forest analysis. Results indicated that PNX-14 and PNX-20 levels were significantly higher in women with PCOS compared to controls (p &lt; 0.001). Both isoforms correlated positively with AMH, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and luteinizing hormone (LH), while demonstrating negative correlations with sex hormone-binding globulin (SHBG) and high-density lipoprotein (HDL) cholesterol. ROC analysis showed moderate discriminatory performance, with area under the curve (AUC) values of 0.834 for PNX-14 and 0.819 for PNX-20. Mediation analysis suggested an associative pattern among PNX isoforms, AMH, and PCOS status. PCA-based clustering identified two distinct phenotypic profiles. Random Forest analysis ranked AMH, SHBG, fasting insulin, and body mass index (BMI) as the most influential variables, with PNX isoforms demonstrating lower importance scores. In conclusion, circulating PNX-14 and PNX-20 were elevated in PCOS and associated with key reproductive and metabolic parameters, suggesting a potential complementary role within multi-marker assessment frameworks. However, given the cross-sectional design and exploratory nature of the analyses, these findings should be considered hypothesis-generating rather than causal. Future longitudinal, mechanistic, and externally validated multicenter studies are essential to further elucidate these relationships.

Periodontitis has been recognized as a contributing factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the precise mechanisms through which periodontitis influences the pathogenesis of MASLD remain unclear. This study aimed to investigate the association between experimental periodontitis and MASLD severity and to explore the potential underlying mechanisms using a ligature-induced periodontitis model under low-fat diet (LFD) and high-fat diet (HFD) conditions. A total of 40 mice were divided into four groups: low-fat diet control group (LFD-Ctrl), low-fat diet with periodontitis group (LFD-Perio), high-fat diet control group (HFD-Ctrl), and high-fat diet with periodontitis group (HFD-Perio), with 10 mice initially assigned to each group. Mice were fed an HFD for 12 weeks to establish the MASLD model, followed by ligature-induced periodontitis for 4 weeks. Periodontal inflammation and alveolar bone loss were assessed using micro-computed tomography (Micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining, while MASLD severity was evaluated via hepatic H&E staining, Oil Red O staining, periodic acid-Schiff (PAS) staining, Masson's Trichrome staining, nonalcoholic fatty liver disease activity score (NAS), alpha-smooth muscle actin (α-SMA) expression, pericellular fibrosis, and serum lipid and liver enzyme measurements. Compared with HFD-Ctrl mice, HFD-Perio mice exhibited aggravated MASLD-related phenotypes, including elevated fasting blood glucose, significantly increased homeostatic model assessment for insulin resistance (HOMA-IR) (2.89 ± 0.67 vs. 1.93 ± 0.26, P < 0.0001), higher nonalcoholic fatty liver disease activity score (NAS) (4.57 ± 0.71 vs. 2.30 ± 0.33, P < 0.01), and more pronounced pericellular fibrosis. Gut microbiota analysis showed that the Firmicutes/Bacteroidota ratio was further increased in HFD-Perio mice compared with HFD-Ctrl mice (9.39 ± 2.82 vs. 5.48 ± 1.98, P < 0.05), accompanied by enrichment of the genus Helicobacter. These findings indicate that experimental periodontitis aggravates HFD-induced MASLD phenotypes, potentially via metabolic dysregulation, liver inflammation and fibrosis, and gut microbiota dysbiosis, highlighting the need for further studies to clarify whether periodontal health influences MASLD progression.

Second-generation antipsychotics, a cornerstone of psychiatric disorder management, render treated patients highly prone to metabolic abnormalities. To address this unmet clinical need, this post-hoc analysis drew on data from a previous trial to examine the correlations between plasma short-chain fatty acid (SCFA) level alterations and metabolic changes in the context of probiotic-fiber intervention. In this trial, individuals diagnosed with schizophrenia or bipolar disorder, who were undergoing stable atypical antipsychotic therapy, were recruited for this study. They were subsequently randomized in a 1:1:1:1 ratio to four treatment groups: combined probiotics (1680mg/d) and dietary fiber (60g/d); probiotics (1680mg/d) with dietary fiber placebo; dietary fiber (60g/d) with probiotics placebo; and double placebo (probiotics placebo plus dietary fiber placebo). Assessments were conducted at screening/baseline, week 4, and week 12, and the measurement of circulating SCFAs was performed via liquid chromatography-mass spectrometry. The analysis, employing the last-observation-carried-forward method, encompassed 79 participants who provided at least one follow-up plasma sample for the quantification of SCFAs. The 12-week combined administration of probiotics and dietary fiber was associated with changes in circulating levels of SCFAs and improvements in metabolic indices. More importantly, the higher levels of propionate were associated with decreased weight (adjusted odds ratio [OR]: 0.61 per quartile increase, 95% confidence interval [CI]: 0.38-0.96) and homeostatic model assessment of insulin resistance (HOMA-IR) (adjusted OR:0.58, 95% CI: 0.36-0.94). Also, the higher levels of butyrate were associated with a 42% lower odds (adjusted OR: 0.58, 95%CI:0.36-0.93) of elevated body mass index (BMI) and a 49% lower odds (adjusted OR: 0.51, 95%CI:0.31-0.86) of elevated insulin levels. The findings of this study suggested that elevated circulating levels of butyrate and propionate might be associated with reduced weight gain and improved insulin resistance in individuals receiving antipsychotic medications. ClinicalTrials.gov NCT03379597, trial registration date: 11/29/2017. Overall Recruitment Status: completed.

Telomir-Zn restores glucose homeostasis and reduces insulin resistance in a diet-induced zebrafish model of type 2 diabetes.