Homeostasis Model Assessment-insulin Resistance Index Research Articles

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1β (interleukin 1β), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1β levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up. Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

Non-Insulin-Based Indices of Insulin Resistance for Predicting Incident Albuminuria: A Nationwide Population-Based Study.

Studies have shown that incident albuminuria is associated with insulin resistance (IR); however, an IR marker that best predicts the prevalence of albuminuria has not yet been established. This study explored the association between IR and incident albuminuria using various IR indices, including the homeostasis model assessment of IR (HOMA-IR), metabolic score for IR (METS-IR), and triglyceride-glucose (TyG) index, and compared their predictive abilities for the prevalence of albuminuria. A total of 4,982 Korean adults from the 2019 Korea National Health and Nutritional Examination Survey were analyzed. The odds of albuminuria were determined using the quartiles of the IR indices. Receiver operating characteristic (ROC) curves were used to calculate the area under the ROC curve and predictability. The cutoff values for albuminuria detection were also computed. An increase in the quartiles of all three IR indices was associated with incident albuminuria, even after full adjustment for covariates (HOMA-IR: odds ratio [OR], 1.906; 95% confidence interval [CI], 1.311-2.772; P=0.006; METS-IR: OR, 2.236; 95% CI, 1.353-3.694; P=0.002; TyG index: OR, 1.757; 95% CI, 1.213-2.544; P=0.003). The area under the ROC curve for incident albuminuria based on the HOMA-IR, METS-IR, and TyG indices was 0.594 (95% CI, 0.568-0.619), 0.633 (95% CI, 0.607-0.659), and 0.631 (95% CI, 0.606-0.656), respectively. The optimal cutoff values for predicting albuminuria were 2.38, 35.38, and 8.72 for the HOMA-IR, METS-IR, and TyG indices, respectively. The METS-IR and TyG indices outperformed HOMA-IR in predicting incident albuminuria.

Associations of Alanine Aminotransferase/Aspartate Aminotransferase, a Marker of Hepatosteatosis, with Adipose Tissue Insulin Resistance Index and Leptin/Adiponectin Ratio in Japanese Women.

Objective: We assessed whether alanine aminotransferase/aspartate aminotransferase (ALT/AST), a marker of hepatic steatosis, may be associated with adipose tissue dysfunction more closely than hepatic and muscle insulin resistance (IR). Methods: Associations with adipose tissue IR index (AT-IR) calculated as a product of fasting insulin and free fatty acids, leptin/adiponectin ratio, a proxy of adipocyte dysfunction, homeostasis model assessment IR (HOMA-IR), hepatic and muscle IR inferred from plasma insulin kinetics during a 75 grams oral glucose tolerance test (OGTT) were studied in nondiabetic 307 young and 148 middle-aged Japanese women, whose body mass index averaged 20 and 22 kilograms/m2, respectively. Results: On multivariate linear regression analysis in young women, ALT/AST was associated with trunk/leg fat ratio (standardized β = 0.202, P = 0.007), a marker of abdominal fat accumulation, and AT-IR (standardized β = 0.185, P = 0.003) independently of HOMA-IR and Matsuda index (R2 = 0.07). In middle-aged women, leptin/adiponectin ratio (standardized β = 0.446, P < 0.001) and AT-IR (standardized β = 0.292, P = 0.009) emerged as determinants of ALT/AST independently of trunk/leg fat ratio, OGTT-derived hepatic IR, leptin, and adiponectin (R2 = 0.34). Conclusions: ALT/AST was associated with AT-IR and adipocyte dysfunction more closely than hepatic and muscle IR even in nondiabetic lean Japanese women.

Circulating mir-199-3p screens the onset of type 2 diabetes mellitus and the complication of coronary heart disease and predicts the occurrence of major adverse cardiovascular events

BackgroundCoronary heart disease (CHD) is a major complication of type 2 diabetes mellitus (T2DM), which causes an adverse prognosis. There is an urgent need to explore effective biomarkers to evaluate the patients’ adverse outcomes.ObjectiveThis study aimed to identify a novel indicator for screening T2DM and T2DM-CHD and predicting adverse prognosis.Materials and methodsThe study enrolled 52 healthy individuals, 85 T2DM patients, and 97 T2DM patients combined with CHD. Serum miR-199-3p levels in all study subjects were detected with PCR, and its diagnostic significance was evaluated by receiver operating curve (ROC) analysis. The involvement of miR-199-3p in disease development was assessed by the Chi-square test, and the logistic regression analysis was performed to estimate the risk factor for major adverse cardiovascular events (MACE) in T2DM-CHD patients.ResultsSignificant downregulation of miR-199-3p was observed in the serum of both T2DM and T2DM-CHD patients, which discriminated patients from healthy individuals and distinguished T2DM and T2DM-CHD patients. Reduced serum miR-199-3p was associated with the increasing blood glucose, glycated hemoglobin (HbA1c), and homeostasis model assessment-insulin resistance index (HOMA-IR) of T2DM patients and the increasing triglycerides (TG), low-density lipoprotein (LDL), fibrinogen, and total cholesterol (TC) and decreasing high-density lipoprotein (HDL) of T2DM-CHD patients. miR-199-3p was also identified as a biomarker predicting the occurrence of MACE.ConclusionDownregulated miR-199-3p could screen the onset of T2DM and its complication with CHD. Reduced serum miR-199-3p was associated with the severe development of T2DM and T2DM-CHD and predicted the adverse outcomes of T2DM-CHD patients.

Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Insulin Resistance-Related Indices in the Japanese Population.

Background: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), which is based on evidence of hepatic steatosis and any of the following three conditions: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation, has been proposed. It is uncertain how indices that predict insulin resistance (IR) are associated with MAFLD. Methods: Among subjects who had undergone health examinations at our hospital, 1,257 (787 men and 474 women) who underwent fatty liver evaluation, were included in this cross-sectional study. The discriminatory ability of each index for MAFLD was tested using a receiver operating characteristic curve analysis. The associations between the homeostasis model assessment-IR (HOMA-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride-glucose (TyG) index, and MAFLD were investigated using multiple logistic regression analysis. Results: The mean age and body mass index of MAFLD subjects were 58.1 years and 26.0 kg/m2 in men and 63.0 years and 26.1 kg/m2 in women, respectively. The cutoff values of HOMA-IR, TG/HDL-C ratio, and TyG index in men and women were 1.40 (area under the curve [AUC]: 0.81) and 1.90 (AUC: 0.88); 1.56 (AUC: 0.75) and 1.06 (AUC: 0.78); and 8.62 (AUC: 0.75) and 8.45 (AUC: 0.80), respectively. All indices were significantly higher in both men and women with MAFLD. In the multivariate models, the odds of MAFLD were higher among both men and women in the highest tertile than those in the lowest tertile. When subjects were divided by sex, presence of MAFLD, and alanine aminotransferase (ALT) values, all indices were significantly higher in both men and women with high ALT levels who were diagnosed with MAFLD. Conclusion: IR strongly correlated with MAFLD, particularly in subjects with high ALT levels.

ASSOCIATION OF HBA1C, SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR, INSULIN RESISTANCE IN PREDIABETES, DIABETES, AND DIABETIC RETINOPATHY PATIENTS

Background: In the micro- and macrovascular pathophysiology of diabetes mellitus, vascular endothelial growth factor (VEGF) is crucial. It has become recognized as a critical element contributing to the emergence of diabetes-related retinopathy and as a critical prognostic marker for the illness. Aims: The aim of this study is to assess the level of glycated hemoglobin (HbA1c), serum VEGF, insulin resistance (IR) in prediabetes, type-2 diabetic patients without microvascular complications, and diabetic retinopathy patients Methods: Values for serum VEGF, HbA1c, and IR were evaluated. Spearman coefficient correlation was used to perform the correlation. Results: Our results demonstrate that fasting insulin levels were almost completely correlated with homeostasis model assessment index of IR (HOMA-IR) (r=0.99) and highly correlated with homeostasis model assessment of β-cell function (r= −0.84). We also looked at if there was any relationship between blood VEGF levels and biochemical results (HbA1c, total cholesterol, triglycerides, low-density lipoprotein). According to a study, IR and serum levels of VEGF were considerably greater in diabetic patients than in controls. Conclusion: Both prediabetes and type 2 diabetes mellitus (T2DM) patients had elevated serum VEGF levels, and these individuals also had favorable relationships with their HOMA-IR scores. In comparison to controls, prediabetes and T2DM patients may have higher VEGF levels due to increased IR.

One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Effects of Endurance Exercise and Vitamin D Supplementation on Insulin Resistance and Plasma Lipidome in Middle-Aged Adults with Type 2 Diabetes.

(1) Background: We investigated the effects of a 12-week exercise intervention with or without vitamin D supplementation on insulin resistance and the plasma lipidome of participants with type 2 diabetes. We further explored whether the effects of the intervention on glycemic parameters could be associated with the baseline lipidome. (2) Methods: Sixty-one participants were randomly allocated to control (Con), exercise (EX), vitamin D (VD), and EX + VD groups. Multiple glycemic and anthropometric parameters were evaluated before and after intervention. The homeostasis model assessment of insulin resistance (HOMA-IR) was the primary outcome. The plasma lipidome was analyzed before, after, and at an additional 12-week follow-up. Machine learning was applied to establish prediction models for responsiveness of glycemic control. (3) Results: Our interventions failed to improve the HOMA-IR index while fasting glucose was reduced in the EX + VD group (change%, -11.9%; effect size, 0.65; p < 0.05). Both EX and VD interventions altered the plasma lipidome, with EX + VD intervention considerably affecting levels of lyso-phosphatidylcholines and triglycerols containing long-chain unsaturated fatty acids. Such effects could last until 12 weeks after intervention. Notably, there was high inter-individual variability in glycemic parameters including HOMA-IR in response to the interventions, which could be predicted with great accuracy using an optimal panel of baseline lipid predictors alone or in combination with clinical indices, as assessed by an area under the receiver operating characteristic curve value of over 0.9. (4) Conclusions: Although substantial alterations were observed in the plasma lipidome related to glycemic control, our intervention failed to improve HOMA-IR scores, which may have been predominately due to the large inter-individual variability in responses. Basal plasma lipid levels could potentially predict an individual's response to intervention, highlighting the necessity of personalized nutrition.

Effect of zinc supplementation on blood sugar control in the overweight and obese population: A systematic review and meta-analysis of randomized controlled trials

BackgroundAlthough overweight and obese people have a higher risk of type 2 diabetes incidence than normal-weight individuals, the efficacy of zinc supplementation in blood sugar control in overweight and obese people remained unknown. This meta-analysis attempted to address this issue. MethodsDatabases including PubMed, Embase, and the Cochrane Library were searched from inception until May 2022 to identify randomized controlled trials (RCTs) investigating the effects of zinc supplementation among participants who were overweight or obese without language restriction. It is a random-effect meta-analysis that analyzed the impact of zinc supplementation on fasting glucose (FG) (i.e., primary outcome) and other variables including fasting insulin (FI), homeostasis model assessment-insulin resistance index (HOMA-IR), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and 2-hour postprandial glucose (2 h- PG). ResultsAnalysis of 12 eligible RCTs involving 651 overweight/obese participants demonstrated that zinc supplementation significantly improves FG (weighted mean difference [WMD]: −8.57 mg/dL; 95% confidence interval [CI]: −14.04 to −3.09 mg/dL, p = 0.002), HOMA-IR (WMD: −0.54; 95% CI: −0.78 to −0.30, p < 0.001), HbA1c (WMD: −0.25%; 95% CI: −0.43% to −0.07%, p = 0.006), and 2 h-PG (WMD: −18.42 mg/dL; 95% CI: −25.04 to −11.79 mg/dL, p < 0.001) compared to those in the control group. After conducting subgroup analyses, we found that the primary outcome, FG, showed more significant results in the subgroups with Asia, Zinc supplementation alone, higher dose (≥30 mg) and patients with diabetes. ConclusionOur meta-analysis indicated that zinc supplementation benefits blood sugar control in overweight and obese populations, with an especially significant reduction in FG.

Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population

Polycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O–H–P, H–P, O–H, and O–P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18–40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O–H–P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02–6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O–H–P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.

#2937 INDIRECT INSULIN RESISTANCE INDICES AND THEIR CUT-OFF VALUES FOR POST-TRANSPLANTATION DIABETES MELLITUS IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Insulin resistance determination in kidney transplant recipients (KTRs) plays an important role to identify KTRs at risk of posttransplantation diabetes mellitus (PTDM) development. Current methods to measure insulin resistance include the hyperinsulinemic-euglycemic (HIEG) clamp technique, and minimal model approximation of the metabolism of glucose (MMAMG). These methods, however, require considerable time and are expense, complex, and invasive. As a result, indirect insulin resistance indices such as homeostasis model assessment-insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), or triglycerides-glucose (TyG) index, are used in epidemiological and clinical studies in the general population due to their simplicity and ease of use. However, it is unknown to what extent those indices may contribute to determine insulin resistance and PTDM development in KTRs. Therefore, this study aimed to investigate the role of indirect insulin resistance indices to determine insulin resistance and PTDM development in KTRs. Method We included 472 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Crude and multivariable Cox proportional hazards regression analysis were performed to determine whether indirect insulin resistance indices (HOMA-IR, VAI, LAP, and TyG index) were prospectively associated with incident PTDM. We analyzed each measure using receiver operating characteristic (ROC) curve for the development of PTDM. The cut-off value was determined as the value with the highest Youden index score in the specificity dominant area. Results During a median 9.6 years [interquartile range (IQR) 6.6–10.2] of follow up, 68 (14%) KTRs developed PTDM. In Cox regression analyses, all indirect insulin resistance indices associated with incident PTDM, independent of potential confounders. ROC curve was 0.764 (95% CI,0.703-0.826) for HOMA-IR, 0.685 (95% CI,0.615-0.757) for VAI, 0.743 (95% CI,0.678-0.808) for LAP, and 0.698 (95% CI,0.629-0.766) for TyG index, with no significant difference between them (p = 0.05). The cut-off values with their corresponding sensitivity and specificity for each indices are presented in Table 1. To test this cut-off value, the association between the indices and incident PTDM was examined by using each index as a categorical variable (HOMA-IR&amp;lt;2.47 vs ≥2.47; VAI&amp;lt;4.01 vs ≥4.01; LAP&amp;lt;87.04 vs ≥87.04; TyG index&amp;lt;4.94 vs ≥4.94). Indirect insulin resistance indices as a categorical variable predicted incident PTDM independent of age, sex, smoking, time to transplantation, systolic blood pressure, eGFR, and medication. Conclusion Indirect insulin resistance indices could be used to predict incident PTDM in KTRs. In addition to HOMA-IR, insulin-free surrogates of insulin resistance might serve as useful methods to identify KTRs at risk for PTDM development.

Ganjiang Huangqin Huanglian Renshen Decoction improves insulin sensitivity by regulating intestinal flora in rats with Type 2 diabetes mellitus

Purpose: To study the effect of Ganjiang Huangqin Huanglian Renshen Decoction (GHHRD) on intestinal microflora and insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats. &#x0D; Methods: Streptozotocin (STZ) injection was used to establish a rat model of T2DM. The T2DM rats were divided into 5 groups: control, T2DM, T2DM + low-dose traditional Chinese medicine (TCM), T2DM + high-dose TCM, and T2DM + metformin groups. Total DNA kit was used for extraction of total DNA from fecal microorganisms from the T2DM model rats. High-throughput 16S rDNA sequencing was carried out to identify the intestinal flora of T2DM model rats. Fasting plasma glucose (FPG) and fasting serum insulin (FINS) levels were determined by a biochemical analyzer. &#x0D; Results: The 16S rDNA sequencing analysis showed that after GHHRD treatment, the levels of Ruminococcus, Prevotellaceae, Escherichia-Shigella and Bacteroidota in the intestinal tract of T2DM model rats exhibited significant changes. Furthermore, GHHRD decreased the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index and IR in T2DM model rats. &#x0D; Conclusion: GHHRD mitigates IR in T2DM model rats through alterations in the intestinal flora of the rats. This provides a theoretical basis for the potential use of GHHRD in the clinical management of T2DM.

Establishing reference values for percentage of appendicular skeletal muscle mass and their association with metabolic syndrome in Korean adolescents.

The association between appendicular skeletal muscle mass (ASM) and cardiometabolic risk has been emphasized. We estimated reference values of the percentage of ASM (PASM) and investigated their association with metabolic syndrome (MS) in Korean adolescents. Data from the Korea National Health and Nutrition Examination Survey performed between 2009 and 2011 were used. Tables and graphs of reference PASM were generated using 1,522 subjects, 807 of whom were boys aged 10 to 18. The relationship between PASM and each component of MS in adolescents was further analyzed in 1,174 subjects, 613 of whom were boys. Moreover, the pediatric simple MS score (PsiMS), the homeostasis model assessment of insulin resistance (HOMA-IR), and the triglyceride-glucose (TyG) index were analyzed. Multivariate linear and logistic regressions adjusting for age, sex, household income, and daily energy intake were performed. In boys, PASM increased with age; the trend was different in girls, in whom PASM declined with age. PsiMS, HOMA-IR, and TyG index showed inverse associations with PASM (PsiMS, β=-0.105, P<0.001; HOMA-IR, β=-0.104, P<0.001; and TyG index, β=-0.013, P<0.001). PASM z-score was negatively associated with obesity (adjusted odds ratio [aOR], 0.22; 95% CI, 0.17-0.30), abdominal obesity (aOR, 0.27; 95% CI, 0.20-0.36), hypertension (aOR, 0.65; 95% CI, 0.52-0.80), and elevated triglycerides (aOR, 0.67; 95% CI, 0.56-0.79). The probability of acquiring MS and insulin resistance decreased as PASM values increased. The reference range may offer clinicians information to aid in the effective management of patients. We urge clinicians to monitor body composition using standard reference databases.

Therapeutic exploration of polyherbal formulation against letrozole induced PCOS rats: A mechanistic approach

ObjectiveThis study aimed to develop an effective alternative medicine with multi potential herbs against polycystic ovarian syndrome (PCOS) in rats induced by letrozole treatment. Materials and methodPolyherbal syrup was prepared with a combination of S. asoca bark, G. sylvestre leaves, P. daemia aerial parts, C. zeylanium stem bark, C. bonduc seeds, and W. somnifera roots ethanolic extract. In vitro cell viability study, adenosine monophosphate-activated protein kinase (AMPK), and glucose transporter 4 (GLUT4) gene expression assay were carried out on the Chinese Hamster Ovarian (CHO) cell line. For the PCOS induction letrozole (1 mg/kg p. o.) was given for 21 consecutive days. The PCOS induction was confirmed by measuring estrus irregularity, insulin resistance by oral glucose tolerance test (OGTT), and hyperandrogenism by measuring serum total testosterone level 21 days after completion of letrozole treatment. After induction of PCOS, metformin (155 mg/kg p. o.), and polyherbal syrup (100 mg/kg, 200 mg/kg, and 400 mg/kg p. o.) were administered for further 28 days. The treatment efficacy was measured by measuring serum lipid profile, fasting insulin level, sex hormones level, ovarian steroidogenic enzymes, ovarian tissue insulin receptor, AMPK, and GLUT4 protein expression levels, and histomorphological studies. The post-treatment effect was confirmed by reproductive performance studies. ResultsLetrozole-induced PCOS rats showed significant estrus irregularity, abnormal sex hormones levels, and hyperandrogenism indicated by showing increased free androgenic index and decreased sex hormones binding globulin (SHBG) level. The insulin resistance in PCOS rats was indicated by increased fasting glucose levels with impaired glucose clearance in the OGT test. Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR) increased level, also decreases INSR, GLUT4, and AMPK mRNA expression in ovarian cells confirming the insulin resistance in PCOS rats. Ovarian histology in PCOS rats also showed many follicular cysts, atretic follicles, and the absence of corpus luteum. The administration of polyherbal syrup, in a dose-dependent manner, effectively restored these alterations. The treatment of polyherbal formulation 400 mg/kg possesses highly significant efficacy over the treatment of metformin in PCOS rats. It mainly acts by reducing peripheral and ovarian hyperandrogenism and improves insulin sensitivity via activating the insulin receptor and AMP-activated kinase-mediated transcription and translation of GLUT4 from the cytoplasm to the ovarian membrane improves glucose uptake and promotes the follicular development and ovulation. The higher fertility rate, delivery index, and survival of delivered pups confirm the broader and superior efficacy of PCOS. These beneficial actions are mainly attributable to the formulation's inclusion of the key secondary metabolites flavonoids and phytosterols. In conclusion, the prepared polyherbal syrup was found to be the safest and most effective alternative medicine for both endocrinal and metabolic complications of PCOS women.

Association between HOMA-IR and ovarian sensitivity index in women with PCOS undergoing ART: A retrospective cohort study.

Insulin resistance (IR) may play a central role in the pathophysiology of polycystic ovary syndrome (PCOS). Controlled ovarian stimulation (COS) in PCOS women in the setting of assisted reproductive technology (ART) is always a challenge for clinicians. However, it remains unclear whether IR in women with PCOS correlates with reduced ovarian sensitivity to exogenous gonadotropin (Gn). This study aimed to explore the association between homeostasis model assessment of insulin resistance (HOMA-IR) and ovarian sensitivity index (OSI). In this retrospective cohort study, we explored the association between Ln HOMA-IR and Ln OSI based on smoothing splines generated by generalized additive model (GAM). Then the correlation between HOMA-IR and OSI was further tested with a multivariable linear regression model and subgroup analysis. 1508 women with PCOS aged 20-39 years undergoing their first oocyte retrieval cycle were included consecutively between 2018 until 2022. We observed a negative association between Ln HOMA-IR and Ln OSI by using smoothing splines. In multivariable linear regression analysis, the inverse association between Ln HOMA-IR and Ln OSI was still found in PCOS women after adjustment for potential confounders (β = -0.18, 95% CI -0.25, -0.11). Compared with patients with the lowest tertile of HOMA-IR, those who had the highest tertile of HOMA-IR had lower OSI values (β = -0.25, 95% CI -0.36, -0.15). Our study provided evidence for the inverse correlation between IR and the ovarian sensitivity during COS in PCOS women. Herein, we proposed new insights for individualized manipulation in PCOS patients with IR undergoing ART.

The Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP) Are Predictors of Insulin Resistance and Hyperandrogenaemia in Obesity/Overweight Women with Polycystic Ovary Syndrome.

Hyperandrogenaemia and insulin resistance (IR) are the main characteristics of polycystic ovary syndrome (PCOS). Here, we study to find appropriate markers predicting IR and hyperandrogenaemia of women with PCOS in northwest China. According to body mass index (BMI), 953 patients with PCOS were divided into two groups. All the patients underwent physical examination and ultrasonography and collected elbow vein blood. Their BMI, waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), LAP, VAI, homeostasis model assessment index of insulin resistance (HOMA-IR), and free androgen index (FAI) were calculated. Each group (normal weight and obesity/overweight) was further divided into two subgroups according to their HOMA-IR and FAI: the IR+ subgroup/IR- subgroup and FAI+ subgroup/FAI- subgroup. Furthermore, we compared the clinical indices, hormone levels, and metabolic makers separately between these groups. The correlations between these parameters and HOMA-IR or FAI were tested; sensitivity, specificity, and receiver-operating characteristic (ROC) curves were calculated. In the obesity/overweight group, the VAI (best cut-off value: 2.27, area under the curve (AUC) = 0.699) and LAP (best cut-off value: 45.54, AUC = 0.680) were sensitive predictors of IR (sensitivity = 72% and sensitivity = 67%). Additionally, the VAI (best cut-off value: 2.13, AUC = 0.624) and LAP (best cut-off value: 51.18, AUC = 0.582) were sensitive predictors of FAI (sensitivity = 87% and sensitivity = 64%). In the normal weight group, BMI could preferably predict HOMA-IR (AUC = 0.717, best cut-off value: 21.62) and HOMA-IR could preferably predict FAI (best cut-off value: 2.11, AUC = 0.648). Our data indicated that the VAI and LAP may contribute to the early identification of IR and hyperandrogenaemia in the obesity/overweight patients of PCOS. In normal weight PCOS, BMI was a better predictor to IR, and HOWA-IR was a better predictor to FAI.

Mediation of Systemic Inflammation on Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke.

Insulin resistance is associated with stroke recurrence and poor functional outcomes of nondiabetic patients with ischemic stroke. The study aimed to investigate whether the association between insulin resistance and the prognosis of nondiabetic patients with ischemic stroke was mediated by systematic inflammation. Patients with ischemic stroke but without a history of diabetes who were enrolled in CNSR-III (Third China National Stroke Registry) were included in the study and followed up for 1 year after stroke onset. Insulin resistance was determined by using the homeostasis model assessment for insulin resistance (HOMA-IR) method. hs-CRP (high-sensitivity C-reactive protein) and Lp-PLA2 (lipoprotein-associated phospholipase A2) activity were measured at baseline. The primary outcome was stroke recurrence, and other outcomes included composite vascular events, mortality, and poor functional outcome (modified Rankin Scale score, 3-6). Multivariable Cox or logistic regression analyses were performed to estimate the association between HOMA-IR and the study outcomes. A mediation analysis was performed to examine the relationship between insulin resistance and the study outcomes mediated by systemic inflammation. Among a total of 3808 nondiabetic patients with ischemic stroke who were included in the study, the median HOMA-IR was 1.79 (interquartile range, 1.05-2.97). After adjustments for potential confounders, higher HOMA-IR quartiles were associated with higher risks of stroke recurrence, ischemic stroke, and composite vascular events, especially in the large artery atherosclerosis subtype. hs-CRP partially mediated the association between the HOMA-IR index and the prognosis of ischemic stroke (mediation proportion, 5.9% for stroke recurrence and 7.5% for composite vascular events). No evidence of Lp-PLA2 activity mediating the association of insulin resistance with stroke outcomes was observed. Our study found that insulin resistance was associated with poor clinical outcomes in nondiabetic patients with ischemic stroke, which was partially mediated by hs-CRP with a modest amount.

Effectiveness of a Lifestyle Change Program on Insulin Resistance in Yaquis Indigenous Populations in Sonora, Mexico: PREVISY.

To evaluate the effectiveness of the healthy lifestyle promotion program for Yaquis (PREVISY) on insulin resistance in the short- and medium-term periods in adults who are overweight/obese and have an increased risk for diabetes. Using a translational research design, an intervention program was implemented in a sample of 93 Yaqui adult subjects. The effectiveness of PREVISY was evaluated by comparing the levels of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Triglycerides-Glucose Index (TyG index) at 6 and 12 months using a paired t-test. Results: In the subjects who completed the program, a decrease in the HOMA-IR index (∆ = -0.91 and ∆ = -1.29, p ≤ 0.05) and the TyG index (∆ = -0.24 y ∆ = -0.20, p ≤ 0.05) was observed in the short- and medium-term period, respectively. Subjects with body weight loss ≥ 10% showed decreased levels of HOMA-IR (∆ = -3.32 and ∆ = -4.89, p ≤ 0.05) and the TyG index (∆ = -0.80 and ∆ = -0.60, p ≤ 0.05) at 6 and 12 months, respectively. A stronger benefit of the program was found in subjects with obesity (vs. overweight) and with high and very high risk of diabetes (vs. moderate risk) in IR markers (p ≤ 0.05). The PREVISY program demonstrated its effectiveness in the improvement of some markers of insulin resistance in Yaqui adults at risk of diabetes.