The potential role of serum miR-182-5p and miR-127-5p in diagnosis of metabolic dysfunction-associated steatotic liver disease and its relationship with insulin resistance.

While metabolic dysfunction-associated fatty liver disease (MAFLD) includes the homeostatic model assessment for insulin resistance (HOMA-IR) as one of the criteria to define metabolic dysregulation, the newly proposed metabolic dysfunction-associated steatotic liver disease (MASLD) has removed this criterion. We investigated whether the HOMA-IR can serve as an independent predictive marker for significant fibrosis in subjects with MAFLD. This is a cross-sectional multicenter study. We enrolled a total of 364 patients diagnosed with MAFLD. We conducted a multiple logistic regression analysis to assess the relationship between HOMA-IR and advanced stages of liver fibrosis (F ≥ 2), as assessed by the FIB-4 score and liver stiffness measurement (LSM). Each unit increase in insulin resistance, as measured by HOMA-IR, was associated with a 16% higher likelihood of displaying significant fibrosis, as determined by a non-invasive scoring test, regardless of diabetes or BMI status. HOMA-IR was independently associated with significant fibrosis in non-diabetic (OR: 1.14, 95% CI: 1.07-1.21, P < 0.001) and diabetic (OR: 1.03, 95% CI: 1.00-1.06, P = 0.03) patients. Moreover, significant fibrosis in lean was independently linked to HOMA-IR (OR: 1.06, 95% CI: 1.01-1.12, P = 0.03) and non-lean (OR: 1.04, 95% CI: 1.02-1.07, P < 0.001) patients. Insulin resistance measured by HOMA-IR should be assessed in patients with MAFLD as a key factor of disease progression and incorporated into the disease diagnostic criteria.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of liver dysfunction and poses a significant risk for progression to cirrhosis. In this study, we aimed to compare the ability of various metabolic indices and identify those most effective for the prediction of MAFLD. This cross-sectional study included 1471 patients (69.6% MAFLD) between 2011 and 2024. Specific metabolic indices were calculated. The associations between indices and MAFLD were analyzed via logistic regression analysis and restricted cubic splines. The prediction ability of the indices was evaluated via receiver operating characteristic (ROC) analysis in different subgroups. Triglyceride glucose (TyG) index, homeostatic model assessment for insulin resistance (HOMA-IR), and estimated glucose disposal rate (eGDR) had the strongest associations with MAFLD (final adjusted ORs for TyG = 3.60, HOMA-IR = 3.35, eGDR = 2.97 per unit change). According to the ROC curve analysis, TyG index and hepatic steatosis index (HSI) had the highest area under the curve (AUC) for the prediction of MAFLD in females (AUC = 0.832) and males (AUC = 0.848), respectively. TyG also performed the best in lean/normal-weight and overweight/obesity individuals, with AUCs of 0.890 and 0.787, respectively. TyG in those ≥ 65years old (AUC = 0.844) and eGDR in those < 65years old (AUC = 0.843) had the highest prediction performance for MAFLD. Insulin resistance markers, including TyG, HOMA-IR, and eGDR, had the strongest associations with MAFLD. For predicting MAFLD, TyG had the highest performance across all subgroups, except for males and those < 65years, where HSI and eGDR performed better, respectively.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been shown to be intimately linked to the presence of insulin resistance. This study aimed to comprehensively evaluate 12 insulin resistance surrogates in relation to MASLD risk and all-cause mortality, utilizing nationwide data from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). This study analyzed 10 303 adults aged greater than or equal to 20 years from the NHANES III (1988-1994) cohort, identifying 2199 individuals with MASLD. The mortality data for this cohort were collected from the National Death Index. Twelve surrogate markers of insulin resistance were evaluated, including triglyceride-glucose (TyG) index, TyG-BMI, TyG-waist circumference, TyG-waist-to-height ratio, C-reactive protein-triglyceride-glucose index, atherogenic index of plasma (AIP), AIP-BMI, AIP-waist circumference, AIP-waist-to-height ratio, estimated glucose disposal rate (eGDR), metabolic score for insulin resistance, and homeostatic model assessment of insulin resistance (HOMA-IR). Statistical analyses employed logistic regression and Cox proportional hazards models to assess associations. Additionally, restricted cubic splines (RCSs) and Kaplan-Meier curves were utilized alongside subgroup and sensitivity analyses. Predictive performance was examined using receiver operating characteristic analysis and machine learning (XGBoost). Among 10 303 participants, MASLD prevalence was 21.3%. In models that have undergone full adjustment, eGDR was negatively correlated with the risk of MASLD [odds ratio = 0.827, 95% confidence interval (CI): 0.780-0.878], while all other indices showed positive associations. In 2199 MASLD patients with 1015 deaths during follow-up, TyG-related indices, C-reactive protein-triglyceride-glucose index, and HOMA-IR were significant correlates with higher all-cause mortality, whereas eGDR was inversely correlated (hazard ratio = 0.887, 95% CI: 0.844-0.933). Two sensitive analyses further supported the overall results in the overall models. The RCS curve exhibited nonlinear dose-response relationships for several indices. XGBoost analyses identified eGDR as the strongest predictor of mortality among insulin resistance surrogates, second only to age. Most insulin resistance surrogates were significantly associated with both MASLD risk and mortality, while eGDR emerged as a robust protective factor with superior predictive performance. These results emphasize the pivotal role of insulin resistance in MASLD and highlight eGDR as a promising noninvasive tool for stratifying risk and predicting adverse outcomes in clinical and public health settings.

Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-associated hepatokine that causes skeletal muscle insulin resistance. Since LECT2 is up-regulated by the inactivation of the energy sensor AMPK in the liver, we hypothesized that LECT2 has potential as a biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, we investigated whether circulating LECT2 levels are associated with insulin sensitivity, liver enzymes, and MASLD. This cross-sectional study included 138 Japanese individuals. Plasma LECT2 levels were measured using fasting blood samples. B-mode ultrasonography was used to assess hepatic steatosis. The mean age and body mass index (BMI) of participants were 63.5 ± 10.2 years and 23.0 ± 3.1 kg/m2, respectively. Higher LECT2 levels positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) values and negatively correlated with the quantitative insulin sensitivity check index (QUICKI) among all participants (HOMA-IR; non-standardized β (B) = 6.38, P < 0.01: QUICKI; B = -161, P < 0.01). These correlations were stronger in the low BMI group (HOMA-IR; B = 13.85, P < 0.01: QUICKI; B = -180, P < 0.01). LECT2 levels also positively correlated with gamma-glutamyl transferase levels (B = 0.01, P = 0.01) and alanine aminotransferase levels (B = 0.33, P = 0.02). Higher LECT2 levels correlated with the prevalence of MASLD (odds ratio = 1.14, P = 0.02). The present results suggest the potential of plasma LECT2 levels as a biomarker for insulin resistance in individuals who are not overweight and the prevalence of MASLD in the general population.

Association between HOMA-IR and metabolic dysfunction-associated steatohepatitis in U.S. adults with MASLD

PurposeAdipose tissue dysfunction is at the center of metabolic dysfunctions associated with obesity. Through studies in isolated adipocytes and mouse models, ATP-binding cassette transporter A1 (ABCA1) expression in the adipose tissue has been shown to regulate high-density lipoprotein (HDL) cholesterol levels in the circulation and insulin sensitivity at both adipose tissue and whole-body levels. We aimed to explore the possible link between ABCA1 expression in the adipose tissue and metabolic derangements associated with obesity in humans.Patients and methodsThis exploratory study among individuals who were lean (body mass index [BMI]: 22.3±0.34 kg/m2, n=28) and obese (BMI: 44.48±5.3 kg/m2, n=34) compared the expression of ABCA1, adiponectin and GLUT4 (SLC2A4) in visceral and subcutaneous adipose tissue using quantitative real-time PCR and immunohistochemistry. Homeostatic model assessment for insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were used as insulin resistance markers.ResultsVisceral adipose tissue from individuals who were obese had significantly lower ABCA1 (P=0.04 for mRNA and protein) and adiponectin (P=0.001 for mRNA) expression compared to that from lean individuals. Subcutaneous adipose tissue did not show any significant difference in the expression. When individuals were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups based on HOMA-IR, IR individuals had lower ABCA1 (P=0.0001 for mRNA and P=0.009 for protein) expression compared to IS individuals in visceral adipose tissue, but not in subcutaneous adipose tissue. The difference was significant after adjusting for age, gender and BMI. ABCA1 mRNA expression in visceral adipose tissue correlated negatively with both HOMA-IR (r=−0.44, P=0.0003) and adipo-IR (r=−0.35, P=0.005) after adjusting for age, gender and BMI. ABCA1 expression in either visceral or subcutaneous adipose tissue did not have any significant correlation with HDL cholesterol levels or mean adipocyte area.ConclusionObesity and insulin resistance are associated with lower expression of ABCA1 in visceral adipose tissue in humans.

The present Research Topic entitled "Mechanistic and Physiological Implications of Insulin Resistance in Metabolic Diseases" aimed to collect the most updated reports in the field of insulin resistance (IR) and metabolic syndrome (MetS). Since the pathophysiological mechanisms of IR remain only partly understood, we herein present a comprehensive understanding of insulin signaling regulation by providing new insights into the impact of altered insulin action on metabolic processes. A cross-sectional study [1] investigated the relationship between triglyceride glucose-body mass index (TyG-BMI) and testosterone levels in adult males, considering TyG-BMI as a novel marker of IR. Using data from the NHANES 2011-2016, the analysis revealed a negative association between TyG-BMI and circulating testosterone levels, even after adjusting for confounders. Testosterone levels were significantly lower in the groups with higher TyG-BMI values. Thus, the ability of the TyG-BMI index to predict testosterone deficiency surpassed that of both the homeostatic model assessment for insulin resistance (HOMA-IR) index and the triglyceride-glucose (TyG) index. Another cross-sectional study [2] explored a practical approach for diagnosing metabolic dysfunctionassociated fatty liver disease (MAFLD). While the exact pathophysiology of MAFLD remains uncertain, IR is a main contributor. Analyzing databases of regular health check-up examinations, researchers investigated the association between MAFLD and four indices, namely: TyG index, fatty liver index (FLI), and modified TyG-related parameters such as TyG-BMI and TyG-waist circumference (TyG-WC). Authors found that modified TyG-related parameters were strongly 36 associated with MAFLD, showing an even predictive power as compared to the TyG index. 37Therefore, modified TyG indices may offer reliable MAFLD prediction daily clinical 38 practice, simplifying diagnosis and improving patient care in real-world settings. 39 40A meta-analysis [3] A retrospective cross-sectional study [4] explored the relationship between IR, hyperinsulinemia, and 51 bone mineral density (BMD) in 437 non-diabetic postmenopausal women. Results showed that 52 elevated HOMA-IR and fasting insulin levels were associated with increased BMD and decreased 53 follicle-stimulating hormone (FSH) values in non-diabetic postmenopausal women. These findings 54 suggest a potential mediating role of IR in FSH-induced BMD suppression in non-diabetic 55 postmenopausal women, leading to a deeper understanding of the mechanisms underlying the BMD 56 decline in postmenopausal women. Thus, it is important to explore strategies for regulating glucose 57 metabolism within an optimal range to promote metabolic and bone health in this population. 58 59Another study [5] investigated the correlation between KLF14 rs4731702 single nucleotide 60 polymorphism (SNP) and the risk of type 2 diabetes mellitus (T2DM) and dyslipidemia across various 61 ethnic groups. Three study groups -healthy subjects, patients with T2DM, and patients with 62 cardiometabolic disorders -underwent biochemical analysis for glycemic and lipid biomarkers, along 63 with genotyping for KLF14 rs4731702 SNP using the Tetra ARMS-PCR method. Results revealed that 64 KLF14 rs4731702 is associated with altered glycemic biomarkers and lipid profile in T2DM patients. 65 Specifically, individuals with the C allele exhibited higher IR and a worse lipid profile as compared to 66 the T allele carriers. This study also found that the prevalence of KLF14

Dehydroepiandrosterone sulfate and insulin resistance in patients with polycystic ovary syndrome

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

BackgroundVisceral obesity is positively related to insulin resistance. The nature of the relationship between waist circumference and insulin resistance has not been known in Japanese populations. This study examined the relationship between waist circumference and insulin resistance and evaluated the optimal cutoff point for waist circumference in relation to insulin resistance in middle-aged Japanese men.MethodsStudy subjects included 4800 Japanese men aged 39 to 60 years. Insulin resistance was evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship of waist circumference with HOMA-IR was assessed by use of adjusted means of HOMA-IR and odds ratios of elevated HOMA-IR defined as the highest quintile (≥2.00). Receiver operating characteristics (ROC) curve analysis using Youden index and the area under curve (AUC) was employed to determine optimal cutoffs of waist circumference in relation to HOMA-IR.ResultsAdjusted geometric means of HOMA-IR and prevalence odds of elevated HOMA-IR were progressively higher with increasing levels of waist circumference. In the ROC curve analysis, the highest value of Youden index was obtained for a cutoff point of 85 cm in waist circumference across different values of HOMA-IR. Multiple logistic regression analysis also indicated that the AUC was consistently the largest for a waist circumference of 85 cm.ConclusionWaist circumference is linearly related to insulin resistance, and 85 cm in waist circumference is an optimal cutoff in predicting insulin resistance in middle-aged Japanese men.

Background Insulin resistance is a common pathway for the development of glucose metabolism disorders and high blood pressure, all of which are components of the metabolic syndrome. The earlier onset of obesity may cause a longer period of insulin resistance, which may explain the concomitant earlier onset of impaired glucose tolerance in young obese people and adolescents so insulin resistance has been implicated as risk factor for metabolic disorders and it is of real importance to develop simple test that can be used in routine clinical setting for identifying insulin resistant individuals in advance so HOMA-IR(Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated haemoglobin) screening to identify young at high risk for insulin resistance and diabetes at an early stage. The study aimed to evaluate the association of HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and HbA1c levels in overweight and nonoverweight young medical students to assess insulin resistance, a condition that can cause diabetes mellitus and metabolic syndrome in earlier life. Subject and Methods The study was systematic random sample was conducted between 40 overweight and 40 non-overweight students (80 in total). All cases were subjected to history taking, clinical examination and laboratory investigations included HOMA-IR and HbA1c. Results Regarding HOMA-IR in present study they illustrated statistically significant difference between groups with higher levels in overweighed group than for normal weight group.HOMA-IR ≥2.5 was represent (17.5%)of normal weight group and (45.0%) of overweighed group with statistically significant difference. N statistically significant difference regarding Glucose (mg/dl) level for normal and overweighed group. The relation was statistically significant regarding Insulin (mIU/ml) level as it was higher in overweighed group than normal group. Regarding HbA1c% in present study; there is no statistically significant difference between normal group compared to obese group that range within normal values with higher result in obese group. Our study found statistically significant association between HOMA-IR&amp;lt;2.5 and (glucose and insulin), in both groups and for HbA1c in obese group. Also statistically significant positive correlation between HOMA-IR and HbA1c% in all patients. Conclusion Obesity is significantly associated with higher levels of fasting insulin, and HOMA-IR values in adolescents. There is a positive correlation between HbA1c and HOMA-IR

Higher PDCD4 expression is associated with obesity, insulin resistance, lipid metabolism disorders, and granulosa cell apoptosis in polycystic ovary syndrome

ObjectiveSystematic evaluation of the efficacy and safety of lower-carbohydrate dietary patterns (LCDP) in metabolic associated fatty liver disease (MAFLD).MethodsThe literature search was conducted in 8 databases, covering all relevant randomized controlled trials on LCDP intervention for MAFLD patients from the database establishment to June 1, 2025. The quality of the literature was evaluated using the Cochrane Bias Risk Assessment Tool. The extracted data were analyzed using Review Manager 5.3 software for meta-analysis. Sensitivity analysis and publication bias detection were performed using Stata 18.0 software.ResultsThe study included 9 randomized controlled trials (RCTs) that met the criteria, involving 408 MAFLD patients and covering 18 outcome measures related to anthropometry, liver function, blood pressure, blood lipids, and blood glucose. The study results indicate that LCDP can significantly affect the body weight (BW) and its 95% confidence intervals (CI) is -4.09 kg[-7.36, -0.81]; waist circumference (WC) -4.84 cm[-5.46, -4.23]; body mass index (BMI) -1.60 kg/m2[-2.41, -0.79]; diastolic blood pressure (DBP) -3.47mmHg[-5.23, -1.71]; triglycerides (TG) -0.45mmol/L[-0.73, -0.17]; fasting plasma glucose (FPG) -0.33mmol/L[-0.60, -0.06] and homeostatic model assessment of insulin resistance (HOMA-IR) -1.57[-2.52, -0.62] levels in patients with MAFLD. Subgroup analysis based on dietary subtypes showed that low carbohydrate diets (LCD) significantly affect the alanine aminotransferase (ALT) -6.82U/L[-12.15, -1.49] levels in MAFLD patients. Very low carbohydrate, high-fat ketogenic diets (VLCKD) can significantly affect the BW -4.62 kg[-8.10, -1.14]; WC -4.90 cm[-5.53, -4.28]; waist-to-hip ratio (WHR) -0.03[-0.05, -0.01]; BMI − 1.68 kg/m2[-2.64, -0.71]; TG -0.56mmol/L[-0.87, -0.24]; glycated hemoglobin (HbAlc) -0.61%[-1.13, -0.09] and HOMA-IR -2.27[-4.01, -0.54] in MAFLD patients. When the LCDP intervention cycle is 8 weeks, it may had no significant effect in MAFLD patients. When the intervention period is 12 weeks, it can significantly affect the BW -6.03 kg[-8.99, -3.07]; WC -4.88 cm[-5.50, -4.26]; BMI − 2.33 kg/m2[-2.61, -2.06]; HOMA-IR -1.44[-2.35, -0.52]; HbA1c -0.61%[-1.13, -0.09]; TG -0.50mmol/L[-0.98, -0.02]; aspartate transaminase (AST) -6.19U/L[-8.85, -3.54] and ALT − 17.09U/L[-26.40, -7.78] in MAFLD patients, and significantly affect the low-density lipoprotein cholesterol (LDL-C) + 0.22mmol/L[0.17, 0.27] in MAFLD patients. Adverse events were reported in 1 trial, commonly including dyspepsia, nausea, and found diet difficult to implement, etc. Although there is some heterogeneity in the study, the results are stable and there is no clear evidence of small-study effects.ConclusionLCDP can improve obesity and insulin resistance (IR) in MAFLD patients, and has a layered mechanism for regulating blood pressure. Its short-term effects on liver enzymes, visceral organs, and liver fat are limited, high saturated fat may weaken its effect on improving serum cholesterol.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12986-025-01065-1.

ObjectiveThe aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk.Methods3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS.ResultsWith the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively.ConclusionsOur data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut-off points in this cohort were developed with variation regarding puberty. HOMA-IR may be useful for early evaluating insulin resistance in children and teenagers and could have a long-term benefit of preventive and diagnostic therapeutic intervention.

Blood concentrations of lipopolysaccharide-binding protein, high-sensitivity C-reactive protein, tumor necrosis factor-α, and Interleukin-6 in relation to insulin resistance in young adolescents