Insulin Resistance Index Research Articles

Arterial stiffness mediates insulin resistance-related risk of atherosclerotic cardiovascular disease: a real-life, prospective cohort study.

The precise pathways connecting insulin resistance (IR) to atherosclerotic cardiovascular disease (ASCVD) remain undefined. The present study aimed to examine the mediating role of arterial stiffness in the association between IR and ASCVD, providing epidemiology insights into the potential mechanisms driving IR to incident ASCVD. A total of 59,777 participants from the Kailuan Study Arterial Stiffness Subcohort who were free of ASCVD at baseline were enrolled in the present study. Arterial stiffness was assessed using baPWV and IR was assessed by triglyceride glucose index (TyG) or metabolic score for insulin resistance (METS-IR). Mediation analysis was adopted to explore the mediating effects of baPWV on the associations between IR and ASCVD and its subtypes. Over a median follow-up of 5.97 years, a total of 2073 cases of ASCVD were identified, with 478 cases of coronary heart disease (CHD) and 1636 cases of ischemic stroke. Mediation analyses revealed that 11.1% of the total association (HR 1.23; 95% CI 1.17 to 1.30) between the TyG index and ASCVD was mediated through baPWV. Specifically, 6.58% and 14.0% of the total associations of the TyG index with CHD and ischemic stroke, respectively, were mediated through baPWV. Similar patterns were observed for METS-IR. These results remained consistent when assessed through causal mediation analysis, time-lagged mediation analysis, and various sensitivity analyses. The association between IR indices and ASCVD was found to be partly mediated by baPWV, indicating a pathway connecting IR to ASCVD outcomes and the potential for interventions targeting arterial stiffness for ASCVD prevention.

Association between insulin resistance indices and outcomes in patients with heart failure with preserved ejection fraction

BackgroundInsulin resistance (IR) plays a pivotal role in the interplay between metabolic disorders and heart failure with preserved ejection fraction (HFpEF). Various non-insulin-based indices emerge as reliable surrogate markers for assessing IR, including the triglyceride-glucose (TyG) index, the TyG index with body mass index (TyG-BMI), atherogenic index of plasma (AIP), and the metabolic score for insulin resistance (METS-IR). However, the ability of different IR indices to predict outcome in HFpEF patients has not been extensively explored.MethodsPatients having HFpEF were recruited from January 2012 and December 2023. The outcome was defined as major adverse cardiovascular event (MACE), encompassing all-cause mortality and rehospitalization for heart failure. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Both univariable and multivariable Cox proportional hazards models were employed to examine the association between the IR indexes and MACE. Furthermore, to assess the incremental prognostic value of the TyG index, we conducted comprehensive analyses using area under the curve (AUC), the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI).ResultsA total of 8693 patients met the inclusion criteria and were included in the final analysis. The mean age of the patients was 70.59 ± 10.6 years, with 5045 (58.04%) being male. The Kaplan-Meier survival analysis revealed that higher degree of the four IR indexes was associated with higher risk of MACE (all log-rank P < 0.05). When treated as a continuous variable, the TyG index showed a significant association with MACE (HR 2.1, 95% CI 1.98–2.23, P < 0.001 in model 1; HR 1.81, 95% CI 1.73–1.9, P < 0.001 in model 2; HR 1.68, 95% CI 1.6–1.76, P < 0.001 in model 3). When categorized into quartiles, the highest quartile of the TyG index (Q4) was significantly associated with MACE (HR 2.48, 95% CI 2.24–2.76, P < 0.001 in model 3). Similar significant associations were found between TyG-BMI, AIP, METS-IR, and MACE. The TyG index was found to enhance the risk stratification capability of the MAGGIC score (AUC from 0.601 to 0.666). When compared to other IR indicators, the TyG index exhibited superior discrimination and reclassification abilities in predicting MACE. Additionally, the TyG-BMI index revealed a U-shaped correlation with MACE, indicating that both an elevated and a lower TyG-BMI index were associated with an increased risk.ConclusionAll four IR indices are independently associated with MACE in patients with HFpEF. Notably, these IR indices significantly enhance the predictive accuracy of the MAGGIC score, a widely used risk assessment tool in HFpEF. Among these indices, the TyG index demonstrated the highest discriminatory and reclassification abilities, providing the greatest incremental value in predicting MACE and exhibiting significant superiority compared to the other indices. These findings highlight the importance of assessing IR indices, particularly the TyG index, in the risk assessment and management strategies for HFpEF patients. However, it should be noted that our findings need to be validated in diverse populations to ensure their applicability and generalizability.Graphical

Anthropometric and metabolic parameters associated with visceral fat in non-obese type 2 diabetes individuals

Background and AimVisceral fat (VF) was proved to be a more precise predictor of atherosclerotic cardiovascular disease (ASCVD) risk in individuals with type 2 diabetes mellitus (T2DM) than body mass index (BMI) itself. Even when the BMI was normal, visceral fat area (VFA) ≥ 90 cm² could raise the ten-year risk of developing ASCVD. Therefore, it was worth evaluating the association of influencing factors with high VF in non-obese T2DM individuals.MethodsThis study enrolled 1,409 T2DM participants with T2DM, of whom 538 had a normal BMI. Based on VFA, these subjects were divided into two groups: VF (+) (VFA ≥ 90cm2) (n = 110) and VF (-) (VFA < 90cm2) (n = 428). The measurement of VFA was conducted using an Omron VF measuring device. Anthropometric and metabolic parameters were detected. Novel insulin resistance indices, such as lipid accumulation product (LAP) was calculated. Factors associated with VF were screened using univariate analysis, multifactorial binary logistic regression models and chi-squared automatic interaction detector decision tree model.ResultsThe VF (+) OB (-) (BMI ≤ 23.9 kg/m2) prevalence were 7.8% in T2DM subjects (n = 1,409) and 20.4% in T2DM subjects with normal BMI (n = 538), respectively. In T2DM subjects with normal BMI, the logistic regression model suggested that neck circumference (NC) had an odds ratio (OR) of 1.891 (95% CI: 1.165–3.069, P = 0.010). The OR for VF gradually increased from the 1st to the 4th in LAP quartile (P < 0.05). LAP emerged as the root node, followed by NC in the decision tree model. Receiver operating characteristic curve (ROC) analysis demonstrated that the area under the curve (AUC) for NC in predicting high VF levels was 0.640 for males and 0.682 for females. Optimal NC cut-off points were 37.75 cm for males and 34.75 cm for females, respectively. Additionally, the AUC values of LAP in predicting high VF levels were 0.745 for males and 0.772 for females, with optimal LAP cut-off points of 22.64 and 26.45 for males and females, respectively.ConclusionThis study identified NC and LAP can be considered predictors of high VF in T2DM subjects with normal BMI.Graphical

Association of estimated glucose disposal rate with metabolic syndrome prevalence and mortality risks: a population-based study

BackgroundInsulin resistance (IR) is a central pathophysiological factor in metabolic syndrome (MetS) and an essential driver of cardiovascular disease (CVD) and mortality. The estimated glucose disposal rate (eGDR) is a reliable marker of IR and has been associated with CVD prognosis. This study aims to examine the relationship between eGDR, MetS, and their predictive roles in clinical outcomes.MethodsData from the NHANES (2001–2018) were utilized, with a cross-sectional design applied to evaluate the association between eGDR and MetS prevalence, and a cohort design employed for mortality follow-up. Weighted logistic regression models were used to examine the association between eGDR and MetS. Weighted Cox proportional hazard models were applied to assess the link between eGDR and both all-cause and CVD mortality. To examine the non-linear associations between the eGDR, MetS, and mortality outcomes, restricted cubic spline (RCS) analysis was applied. Additionally, the predictive performance of eGDR, and other IR indices (TyG, HOMA-IR), for mortality was assessed using the C-statistic.ResultsA robust negative association between eGDR and MetS prevalence was found, following full covariate adjustment (p < 0.001). The core findings were consistent across subgroups (all p < 0.001). Cox regression analysis indicated that in individuals with MetS, each standard deviation (SD) increment in eGDR was associated with an 11% and 18% decrement in the risk of all-cause and CVD mortality, respectively. RCS analysis displayed a non-linear association between eGDR and MetS prevalence, while a linear association between eGDR and mortality. The C-statistic showed that eGDR, compared to the TyG index and HOMA-IR, significantly improved predictive power for all-cause mortality (p = 0.007).ConclusioneGDR is strongly associated with MetS and predicts all-cause and CVD mortality in individuals with MetS. Compared to TyG and HOMA-IR, eGDR offers superior predictive value for all-cause mortality, highlighting its potential as a useful tool in clinical risk assessment.

Shiftwork and insulin resistance in professional drivers: exploring the association using non-insulin-based surrogate measures

BackgroundPrevious research has made use of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index to explore the association between shiftwork (SW) and insulin resistance (IR). However, the limitations of the HOMA-IR index restrict its use. This study aimed to investigate the relationship between SW and IR in professional drivers using four alternative non-insulin-based IR surrogate measures (NIRS), and to determine the predictors of elevated NIRS.MethodsA comparative cross-sectional study was conducted on professional drivers at four Egyptian companies, where 187 SW were compared to 193 dayworkers (DW). Measurements included: sociodemographic, work, and clinical characteristics. Laboratory and NIRS data included: triglyceride glucose (TyG), triglyceride glucose-body mass index (TyG-BMI), triglyceride to high density lipoprotein cholesterol (TG/HDL-C), and metabolic score of insulin resistance (METS-IR). Further assessments included insomnia severity index (ISI), and perceived stress scale (PSS-10).ResultsShiftwork-drivers showed significantly higher levels of NIRS compared to DW-drivers. Shiftwork was significantly associated with elevated TyG (OR: 5.04, 95% CI: 1.98–12.84), TyG-BMI (OR: 4.50, 95% CI: 2.45–8.26), and METS-IR (OR: 6.30, 95% CI: 2.72–14.58). Significant interactions between SW and insomnia or meal-timing habits existed, where SW-drivers with clinically significant insomnia had 11 times higher odds of elevated TyG compared to DW drivers without insomnia. Likewise, SW-drivers experiencing poor meal timing habits had 5.5- and 6.8-times higher odds of elevated TG/HDL-C and METS-IR, respectively, compared to DW divers without poor meal timing habits. Other significant predictors for elevated NIRS included: age, income, stress, overweight/obesity, and poor meal timing habits.ConclusionsThis study demonstrates a significant association between shiftwork and elevated insulin resistance in professional drivers. Insomnia and poor meal timing habits significantly increases the odds of insulin resistance among professional drivers, suggesting interventions targeting sleep quality, meal timing, and stress management.

Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes.

At present, the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent, to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes, the report is as follows. To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis. Metabolic indicators were collected preoperatively, as well as at 3 and 6 months postoperative. The metabolic indicators analyzed included body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), 2-hour blood glucose (PBG), glycated hemoglobin (HbA1c), fasting C-peptide, 2-hour C-peptide (PCP), fasting insulin (Fins), 2-hour insulin (Pins), insulin resistance index (HOMA-IR), β Cellular function index (HOMA-β), alanine aminotransferase, aspartate aminotransferase, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein, and uric acid (UA) levels. SBP, DBP, PBG, HbA1c, LDL-C, and TG were all significantly lower 3 months postoperative vs preoperative values; body weight, BMI, SBP, DBP, FBG, PBG, HbA1c, TC, TG, UA, and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months; and PCP, Fins, Pins, and HOMA-β were all significantly higher 6 months postoperative vs at 3 months (all P < 0.05). Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study

BackgroundPerinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.MethodsThis is a longitudinal, descriptive and analytical study of a cohort with a history of EUGR recruited at prepubertal age and followed up for 10 years until the end of puberty. Anthropometric measurements, blood pressure, biochemical parameters related to lipid and carbohydrate metabolism and plasma adipokines and cytokines were analyzed.ResultsCompared with prepubertal children, young adults EUGR presented increased abdominal circumference percentiles. Moreover, insulin levels and the homeostatic model assessment for insulin resistance (HOMA-IR) index were higher in young adults, with a considerable proportion of participants (22%) becoming insulin-resistant after pubertal development. In contrast, arterial hypertension was observed in 36% of prepubertal children compared with 18% of postpubertal young adults. Lipid values were within normal ranges without differences. Adiponectin and leptin remained at similar levels in adulthood, with a decrease in resistin.ConclusionIndividuals with a history of EUGR have increased metabolic risk in adulthood, which emphasizes the importance of clinical follow-up from childhood to prevent the development of further future associated diseases.

Impact of Berberine Hydrochloride-assisted Metformin on the Metabolism of Glycolipids and Serum Levels of TIMP-1 and TGF-β1 in Individuals with Type 2 Diabetes

Background Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired glucose metabolism, leading to hyperglycemia and increased risk of complications like renal fibrosis. Purpose This study’s purpose is to examine how berberine hydrochloride (BBR) and metformin (Met) work together to treat T2DM, as well as how these medications affect tissue type metalloproteinase-1 (TIMP-1), glucose, and lipid metabolism levels in the blood and transforming growth factor β1. Methods Using a random number table approach, overall, 100 individuals with T2DM between October 2020 and October 2022 were chosen and classified into two groups: An experimental group and an untreated group, each with 50 patients. The untreated group received Met therapy, whereas the experimental group received BBR based on the untreated group. The two groups were compared regarding efficacy, cholesterol and glucose metabolism, renal function and renal fibrosis indices, and the frequency of adverse responses. Results The experimental group’s effective rate was 96.00% higher than that of the untreated group (82.00%). Following treatment, the experimental group had lower levels of glycosylated hemoglobin (HbAlc), insulin resistance index (HOMA-IR), fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and cholesterol (TC) than the untreated group, while the untreated group had greater levels of high-density lipoprotein cholesterol (HDL-C). Following the course of therapy, the observation group’s levels of cystatin (Cys-C), urinary β2 microglobulin (β2-MG), urine albumin excretion rate (UAER), and urinary microalbumin (ALB) were all lesser compared to the untreated group. Following treatment, the experimental group’s transforming growth factor-β (TGF-β) levels, matrix metalloproteinase-9 (MMP-9), and TIMP-1 were lesser than those of the untreated group. Conclusion When Met and BBR are taken together, patients with type 2 diabetes can effectively control their glucose and lipid metabolism, as well as their levels of TGF-β1, MMP-9, and TIMP-1. They can also postpone renal interstitial fibrosis and eventually improve their kidney function, all with a high degree of safety and significant effects.

Associations between surrogate insulin resistance indexes and osteoarthritis: NHANES 2003–2016

Insulin resistance (IR) and abdominal obesity are key in osteoarthritis (OA) development. The triglyceride glucose (TyG) index, along with indicators such as the visceral adiposity index (VAI), and lipid accumulation product (LAP), are increasingly used to measure IR. This study aims to explore the associations between surrogate IR indexes and OA, assessing their diagnostic efficacy within American populations. This study included 14,715 adults from the National Health and Nutrition Examination Survey 2003–2016. Logistic regression models and restricted cubic spline were used to explore the relationship between surrogate IR indexes and OA. Receiver operating characteristic curves were constructed to assess the diagnostic efficacy of these indices, with the area under the curve (AUC) as the metric. TyG, glucose triglyceride-waist circumference (TyG-WC), glucose triglyceride-body mass index (TyG-BMI), glucose triglyceride-waist height ratio (TyG-WHtR), VAI and LAP were significantly and positively associated with the prevalence of OA (all p < 0.01). After adjusting for various potential confounders, TyG-WC, TyG-BMI, TyG-WHtR and LAP remained significantly correlated with the prevalence of OA. Furthermore, restricted cubic spline revealed a nonlinear association between TyG-BMI, TyG-WHtR and LAP (all P-non-linear < 0.05). Receiver operating characteristic curves indicated that TyG-WHtR (AUC 0.633) demonstrated more robust diagnostic efficacy. Additionally, the sensitivity analysis produced results consistent with the primary findings. TyG and its combination with obesity indicators and LAP, are positively associated with the prevalence of OA, with TyG-WHtR showing the highest diagnostic efficacy.

Efficacy of myo-inositol and zinc on insulin resistance in a paediatric population with obesity.

To assess the efficacy of the combined administration of myo-inositol and zinc, a mineral involved in the insulin pathway, in paediatric obesity with insulin resistance on HOMA-IR, glucose-insulin metabolism, and lipid profile. Double-blind, randomized, placebo-controlled study conducted in North Italy. Fifty-six patients (10-18 years, Tanner stage ≥3) with obesity and insulin resistance were randomized to myo-inositol (2000 mg), zinc gluconate (5 mg), and galactooligosaccharides (GOS) from plant-based origin (1000 mg) (TRT) or placebo (PLC) containing only GOS from plant-based origin (1000 mg). All patients received an isocaloric diet following the Mediterranean diet style. Data were collected at baseline (V0) and after 3 months (V1). The primary outcome was the insulin resistance index (HOMA-IR). Fifty out of 56 recruited subjects completed the study. TRT improved HDL cholesterol level compared to PLC (p = 0.05) but not insulin resistance. A stratified post hoc analysis was performed by sex, BMI, and subgroups of adherence to the Mediterranean diet. Subjects were divided for obesity grade, fasting insulin (p = 0.0137) and HOMA-IR (p = 0.0273) were lower in TRT than in PLC patients, with a greater effect on severe obesity. No adverse events were detected. Three months of supplementation with myo-inositol and zinc were beneficial on lipid profile and in managing obesity complications at least in subjects with severe phenotype. Thus, myo-inositol and zinc could be used as non-pharmacological agents. This work suggests a long-term study with a larger sample size to enrich the findings.

Metabolic Status and Hypertension: The Impact of Insulin Resistance-Related Indices on Blood Pressure Regulation and Hypertension Risk

Background Diabetes is closely related to hypertension, and insulin resistance-related indices are novel metrics used to evaluate the risk of diabetes and cardiovascular diseases. This study aims to explore the relationships between the TyG index, METS-IR, TG/HDL-C, and HOMA-IR with hypertension. Methods Data from the NHANES spanning ten consecutive survey cycles from 1998 to 2018 were utilized, focusing on adults with complete blood pressure data and comprehensive information for calculating the TyG index, METS-IR, TG/HDL-C, and HOMA-IR. A multivariable logistic regression model was employed to examine the relationship between insulin resistance indices and hypertension as well as blood pressure levels, while subgroup analyses were conducted to explore potential influencing factors. RCS curves were used to describe both linear and non-linear relationships. Results This NHANES-based study included 16,062 adults. Regardless of the adjustment for covariates, significant associations were found between the TyG index, METS-IR, TG/HDL-C, HOMA-IR and hypertension risk. The ROC curve demonstrated the stability of the TyG index, METS-IR, TG/HDL-C, and HOMA-IR in predicting hypertension risk. The RCS curves uncovered a linear relationship between the TyG index, METS-IR, and hypertension, whereas TG/HDL-C and HOMA-IR exhibited a non-linear association with hypertension. Subgroup analyses indicated that smoking and diabetes may influence the relationship between insulin resistance-related indices and hypertension. Conclusion Elevated levels of the insulin resistance indices TyG index, METS-IR, TG/HDL-C, and HOMA-IR are closely associated with hypertension risk. These indices can serve as effective markers for monitoring hypertension risk in clinical practice. However, larger-scale prospective cohort studies are needed to validate these findings and further explore the clinical application potential of the TyG index, METS-IR, TG/HDL-C, and HOMA-IR as tools for cardiovascular risk assessment. Such studies will help elucidate the specific causal relationships between these insulin resistance-related indices and hypertension and advance their practical application in clinical settings.

Association Between Four Non-Insulin-Based Insulin Resistance Indices and the Risk of Post-Stroke Depression.

Research suggests that insulin resistance (IR) is associated with acute ischemic stroke (AIS) and depression. The use of insulin-based IR assessments is complicated. Therefore, we explored the relationship between four non-insulin-based IR indices and post-stroke depression (PSD). A total of 638 consecutive AIS patients were enrolled in this prospective cohort study. Clinical data were collected to compute indices such as the triglyceride glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI), insulin resistance metabolic score (METS-IR), and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C). One month post-stroke, neuropsychological assessments were conducted using the 17-item Hamilton Depression Scale. Binary logistic regression analysis was performed to explore the relationship between the four non-insulin-based IR indices and PSD. Ultimately, 381 patients completed the 1-month follow-up, including 112 (29.4%) with PSD. The PSD group exhibited significantly higher levels of the four IR indices compared to the non-PSD group. Logistic regression analysis demonstrated that these indicators were independently associated with PSD occurrence, both before and after adjusting for potential confounders (all P < 0.001). Tertile analyses indicated that the highest tertile group had a greater risk of PSD occurrence than the lowest tertile group for four IR indicators, even after adjusting for potential confounders (all P < 0.05). Restricted cubic spline analysis revealed a linear dose-response relationship between the four IR indices and PSD. In the subgroup analysis, only the TyG index showed a significant interaction with diabetes (P for interaction = 0.014). The area under curve values for the TyG index, TyG-BMI, METS-IR, and TG/HDL-C were 0.700, 0.721, 0.711, and 0.690, respectively. High TyG index, TyG-BMI, METS-IR, and TG/HDL-C at baseline were independent risk factors for PSD in AIS. Each of these indicators exhibits predictive value for PSD occurrence, aiding in the early identification of high-risk groups.

Exploring insulin resistance and pancreatic function in individuals with overweight and obesity: Insights from OGTTs and IRTs.

To investigate insulin resistance and pancreatic β-cell function in overweight or obese people under the same glucose tolerance conditions. The subjects were categorized based on the results of the oral glucose tolerance test (OGTT) and the BMI classification criteria. Basal and postprandial glucose concentrations, insulin concentrations, pancreatic β-cell function (HOMA-β), the insulin resistance index (HOMA-IR), and the insulin early secretion index (ΔI30/ΔG30) were compared between the different weight groups. Among individuals with similar glucose tolerances, those in the obese group presented higher HOMA-β, HOMA-IR, and ΔI30/ΔG30 values than did those in the normal weight and overweight groups. Additionally, in individuals with normal glucose tolerance and early diabetes, OGTT 1-h plasma glucose concentrations demonstrated a stronger correlation with early insulin secretion across different body weights. When the same glucose-tolerant population was grouped by weight, OGTTs were significantly less different than IRTs. Therefore, integrating both tests is the optimal approach. In individuals with preobesity, there is an increase in pancreatic β-cell function to maintain normal blood glucose levels. As the disease progresses, obesity substantially increases insulin resistance, which acts as a disease-promoting factor. Furthermore, OGTT 1-h plasma glucose concentrations are strongly correlated with insulin secretion in normal or early diabetic populations.

High-Intensity Interval Training Reduces Liver Enzyme Levels and Improves MASLD-Related Biomarkers in Overweight/Obese Girls.

Despite the abundant body of evidence linking high-intensity interval training (HIIT) to cardiometabolic markers, little is known about how HIIT affects liver enzymes, particularly in obese adolescents. This study aimed to investigate the effects of HIIT on metabolic dysfunction-associated steatotic liver disease (MASLD)-related biomarkers in overweight/obese adolescent girls. Thirty-three overweight/obese adolescent girls (age, 17.0 ± 1.15 yr.; body mass index, 33.3 ± 4.77 kg/m2) were randomly assigned to HIIT (n = 17) or control (n = 16) groups. The HIIT group participated in a nine-week HIIT program (three times weekly) without caloric restriction. Maximal aerobic speed, body composition indexes, blood pressure, MASLD-related biomarkers [liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), plasma lipids, uric acid, platelet count, and homeostasis model assessment index for insulin-resistance (HOMA-IR)] were examined at baseline and after the intervention. Significant "time × group" interactions were found for body composition indexes, systolic blood pressure, maximal aerobic speed, liver enzymes ALT and AST, plasma lipids, glucose, and HOMA-IR. The HIIT program resulted in an increase in maximal aerobic speed (p = 0.035) and a decrease in body composition and plasma lipids (p < 0.01), systolic blood pressure (p = 0.011), ALT (p = 0.013), AST (p = 0.012), and HOMA-IR (p = 0.01), but no significant changes in uric acid and platelet count. None of these markers changed in the control group. HIIT resulted in an improvement in MASLD-related biomarkers. HIIT could be an effective exercise therapy to prevent and reverse MASLD in adolescents with obesity.

Social isolation increases impulsive choice with minor changes on metabolic function in middle-aged rats.

The effects of social isolation (SI) during middle age remain unclear, so we tested the hypothesis that SI would lead to an increase in impulsive choice (IC), anxiety-like behavior, and metabolic dysfunction in middle-aged rats. Male and female rats were housed individually or in groups of four with same-sex housing mates at 11 months of age. Two months later, IC behavior was assessed using a delay-discounting task and anxiety-like behavior through a novelty-suppressed feeding (NSF) task. Lastly, glucose tolerance and insulin sensitivity following exposure to a high-fat diet were assessed using an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). The results showed that socially isolated rats displayed more IC behavior than did group-housed rats of both sexes. However, no significant effect of housing was evident in the NSF task, OGTT, or ITT. Male rats had a higher plasma insulin concentration and insulin resistance index compared to females. Our findings demonstrate that SI in middle age is sufficient to increase IC behavior and highlight inherent sex-specific differences in metabolic profiles. These findings underscore the importance of investigating mechanisms that underlie the effects of social isolation during different stages of life.

Obesity as factor of development of metabolic deviations in gestational diabetes

Objective — to evaluate the pathophysiological role of obesity in the development of metabolic disorders in women with gestational diabetes (GD). Materials and methods. 125 pregnant women were examined, including 33 obese patients, 32 pregnant women with GD, and 37 women with comorbidity of GD and obesity. The control group was represented by 23 practically healthy pregnant women. The content of proinflammatory cytokines (interleukin1b (IL‑1b), IL‑6, IL‑17, tumour necrosis factor a (TNFa)), C‑reactive protein (CRP) and glucometabolic profile were determined. Results. An integral analysis of the incidence structure of degrees of obesity by group established a statistically significant increase in degrees of obesity in women with combined pathology. The HOMA‑IR insulin resistance index was statistically significantly higher in obese patients by 1.1 times (p &lt;0.05) compared with isolated GDM and by 2.5 times (p &lt;0.001) compared with the control group, with a combined course of GDM and obesity — by 1.2 times (p &lt;0.001) and 2.7 times (p &lt;0.001), respectively. The indicators of the obesity group and the comorbidity group differed by 1.1 times (p &lt;0.001). The median CRP content in pregnant women with GD and obesity was 8.12 mg/l, in obese patients — 6.95 mg/l, and in patients with GD — 4.47 mg/l. These results exceeded the control values (2.67 mg/l) by 3.04 (p &lt;0.001), 2.6 (p &lt;0.001) and 1.7 (p &lt;0.001) times, respectively. The results of studying the activity of proinflammatory cytokines showed their significant overexpression in all study groups, but the deviations were more pronounced in women with comorbidities of GD and obesity. Correlations were revealed between parameters of the glucometabolic profile and markers of inflammation, as well as strong positive correlations between body mass index and levels of IL‑17 (r=0.91; p &lt;0.01), IL‑6 (r=0.89; p &lt;0.01), IL‑1b (r=0.94; p &lt;0.01), TNF‑α (r=0.88; p &lt;0.01) and CRP (r=0.86; p &lt;0.01) in women with comorbid pathology. Conclusions. The presence of concomitant obesity in women with GD is characterized by the intensification of the meta‑inflammatory phenotype, which is manifested by significantly more pronounced expression of pro‑inflammatory biomarkers — cytokines IL‑1b, IL‑6, IL‑17, TNF‑α, and CRP, and is associated with statistically deeper deviations of the glucometabolic profile, progression of insulin resistance and deterioration of the course of GD compared to isolated pathology.

Evaluation of metabolic syndrome components, serum uric acid levels and epicardial adipose tissue thickness in pubertal children by severity of obesity.

We aimed to evaluate how the parameters used in the diagnosis of metabolic syndrome (MetS) and parameters such as epicardial adipose tissue (EAT) thickness, insulin resistance (IR), and serum uric acid (SUA) are affected according to the severity of obesity. A total of 120 obese patients aged 10-18 years were classified as class 1-2-3 according to their body mass index (BMI) score. SUA was measured and oral glucose tolerance tests were performed on all patients. MetS components were determined according to the International Diabetes Federation 2007 criteria. IR was calculated using homeostatic model assessment for insulin resistance (HOMA-IR) and whole body insulin sensitivity index (WBISI). HOMA-IR was higher in the class 3 group than in the class 1 (p<0.001) and class 2 groups (p<0.01). WBISI was lower in the class 3 group than in the class 1 (p=0.015) and class 2 groups (p<0.01). EAT thickness was higher in the class 3 group than in the class 1 (p<0.01) and class 2 groups (p<0.01). No significant difference was found between class 1 and 2 groups for HOMA-IR, WBISI, and EAT thickness variables. The frequency of the MetS components was similar between the class of obesity groups (p=0.702). SUA and EAT thickness were significantly higher in the group with 2 and/or more MetS components than in the group with no MetS component. EAT thickness was positively and moderately correlated with SUA levels (Rho=0.319, p<0.001). A more significant increase in cardiovascular disease risk factors, especially after class 2 obesity suggests that obese people should be followed closely and necessary interventions made for the prevention and progression of obesity. SUA and EAT thickness, an important risk factor affecting the obesity-related comorbidities, are positively correlated with each other and can be used in the follow-up of obese children.

Interplay between elevated RAB5B gene expression and insulin resistance among women with PCOS-insights from a case-control study.

Polycystic ovary syndrome (PCOS) represents a multifaceted endocrine, reproductive, and metabolic disorder characterized by hyperandrogenism and hyperinsulinemia-induced insulin resistance (IR). Recent studies reported that the etiology of PCOS is likely correlated with genes involved in steriodogenesis, IR and glucose metabolism. Among the candidate genes in insulin signaling pathways, RAB5B, a small GTPase involved in vesicle trafficking, significantly impacts cellular pathways in ovarian follicular cells, leading to clinical and endocrine changes among women with PCOS. Additionally, RAB5B is crucial for insulin-mediated glucose uptake and is involved in PI3K, AKT, and MAPK/ERK pathways, affecting LHCGR-stimulated steroidogenesis. Despite extensive research, the precise molecular mechanisms underlying RAB5B mediated IR in PCOS remained elusive. The study aimed to explore the potential link between RAB5B gene expression and IR among women with PCOS. A total of age matched 270 subjects were enrolled in this study including 135 PCOS women and 135 apparently healthy controls. These study participants were subjected to detailed medical history, clinical and physical examination. All subjects were further evaluated for biochemical, hormonal and RAB5B gene expression estimation. Expression levels of RAB5B gene were analyzed using gene-specific primers and the SYBR® Green PCR Kit (Qiagen, Germany) and their qPCR reaction mix, according to the manufacturer's guidelines. Student t-test and ANOVA were used to evaluate the differences in the means of various parameters. The HOMA-IR (2.28 ± 1.4 vs. 1.36 ± 0.73) was significantly elevated among women with PCOS than controls (p < 0.05). We also found that the QUICKI (0.35 ± 0.04 vs. 0.37 ± 0.04), MATSUDA (12.59 ± 4.71 vs. 15.47 ± 4.33) and FGIR (11.56 ± 7.06 vs. 14.32 ± 8.66) were higher in controls than women with PCOS (p < 0.05). We also observed that women with PCOS had elevated levels of RAB5B mRNA levels when compared with apparently healthy controls. Bivariate correlation analysis among HOMA-IR stratified PCOS and control subjects revealed strong negative correlation between IR+ PCOS and IR- PCOS (r = -0.61, P < 0.05) and IR- control (r = -0.37, p < 0.05) subjects respectively. Our study demonstrated that there is potential link between RAB5B gene expression and IR specifically in the context of IR indices among women with PCOS.

Triglycerides to apolipoprotein A1 ratio: an effective insulin resistance-associated index in identifying metabolic dysfunction-associated fatty liver disease in type 2 diabetes mellitus

BackgroundThe triglycerides to Apolipoprotein A1 ratio (TG/APOA1) holds promise to be a more valuable index of insulin resistance for the diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus (T2DM). This study aims to evaluate the correlation between TG/APOA1 and MAFLD, as well as compare the efficacy of TG/APOA1 with triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-c) and triglyceride-glucose (TyG) index in identifying MAFLD among individuals with T2DM.MethodThis study consecutively recruited 779 individuals with T2DM for the investigation. The unenhanced abdominal CT scans were conducted to measure CT liver-spleen attenuation measurement (CTL-S). The CTL-S less than 1.0 and without other liver comorbidities were considered to be MAFLD. The binomial logistic regression analysis and restricted cubic spines (RCS) were employed to evaluate the association between TG/APOA1 and MAFLD. The receiver operating characteristic (ROC) curve analysis was performed to compare the efficacy of TG/APOA1 with TG/HDL-c and TyG index identifying MAFLD.ResultsThe TG/APOA1 exhibited a substantial increase in the MAFLD group (P&amp;lt;0.05). Even after adjustments for potential confounding factors, TG/APOA1 exhibited significant associations with nonalcoholic fatty liver disease fibrosis score (β=0.266, P&amp;lt;0.001), fibrosis-4 index (β=0.123, P=0.029), aspartate aminotransferase-to-platelet ratio index (β=0.113, P=0.037), and CTL-S (β=-0.225, P&amp;lt;0.001). Meanwhile, TG/APOA1 contributed to an independent variable for MAFLD, the odds ratio with a 95% CI was 2.092 (1.840-2.380) in the total population, 2.123 (1.810-2.511) in men, and 2.162 (1.824-2.587) in women. Additionally, the results also revealed a nonlinear association between elevated TG/APOA1 and higher MAFLD risk according to the RCS analysis whether in the total population, men, or women (P for nonlinearity and overall &amp;lt;0.001). Furthermore, TG/APOA1 had higher AUC level compared to TG/HDL-c and TyG index in the total population (0.769 vs 0.742, P=0.025; 0.769 vs 0.694, P &amp;lt; 0.001), men (0.776 vs 0.744, P=0.044; 0.776 vs 0.709, P &amp;lt; 0.001), and women (0.762 vs 0.728, P=0.041; 0.762 vs 0.674, P &amp;lt; 0.001).ConclusionTG/APOA1 serves as an effective index of insulin resistance in identifying MAFLD, offering advantages in the screening of MAFLD in T2DM.

Suitability of a new diet-induced model of metabolic syndrome for immunophysiological studies in rats

Studying the pathogenesis of metabolic syndrome and its complications as well as contribution of immune cells to these processes is impossible without relevant laboratory animal models. The nutritional model based on the Western diet was proven to be applicable for these purposes. It correlates with the nutritional pattern of modern humans by reproducing obesity, carbohydrate and lipid metabolism disorders, and low-intensity systemic inflammation. However, this diet involves the use of specialized commercial food, which is currently in limited access, thus requiring the development of a native diet based on the ratio of food ingredients proposed in well-known publications, with efficiency assessment of the selected model. Therefore, the purpose of present study was to evaluate the perspectives of a novel dietary modification based on a Western diet for modeling metabolic syndrome in Wistar rats. The diet of experimental group of rats included 30% standard food, 25% lard, 25% sucrose, 2% salt. The protein fraction in the diet was replenished by adding soy protein. The animals were fed a Western diet for 18 weeks, starting at 8 weeks of age. The examination of animals was based on biometric parameters, general blood counts, biochemical analysis of blood plasma, and histochemical staining of liver sections for lipids. Results: It was found that, starting from 6 weeks, the rats from experimental group significantly exceeded the control ones in the body mass. After 18 weeks, they showed a significant increase in body weight, waist circumference, visceral fat mass compared to the controls, fasting hyperglycemia (with unchanged levels of glycated hemoglobin), along with signs of dyslipidemia (increased levels of triglycerides, LDL and VLDL cholesterol, atherogenic quotient), and increased insulin resistance index HOMA-IR. We could not, however, reproduce the development of fatty hepatosis in experimental rats, which should be considered a limiting factor of the proposed model. The nutritional model of metabolic syndrome based on the Western diet closely resembles the nutritional habits of modern humans. The proposed diet and the exposure time allowed us to achieve the development of the main signs (obesity) and several additional criteria of metabolic syndrome (hyperglycemia, dyslipidemia) in the rat model. Thus, the chosen experimental model may be successfully used to study the immunophysiological aspects of metabolic syndrome. However, the absence of fatty liver disease in experimental animals should be taken into account.