Homeostasis Model Assessment Of Insulin Resistance Research Articles

Relationship of adiponectin, leptin and reproductive endocrine hormones with insulin resistance in polycystic ovary syndrome patients with normal BMI

Objective This study aimed to analyze the correlation of adiponectin (APN) and leptin (LEP), reproductive endocrine hormones with insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI). Methods Totally 160 PCOS patients were categorized into the Normal BMI (BMI: 18.5–25 kg/m2, n = 62) and High BMI (BMI > 25 kg/m2, n = 98) groups. Glucose indicators [fasting plasma glucose, fasting insulin and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)], lipid indicators [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)], adipokines [APN and LEP] and reproductive endocrine hormones [luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), total testosterone (TT), dehy-droepiandrosterone sulfate (DHEAS) and estradiol (E2)] were collected, and their correlations were analyzed. The relationship of HOMA-IR with APN, LEP and reproductive endocrine hormones was subjected to multiple linear regression analysis. Results Correlation analysis revealed positive correlations of HOMA-IR with TC, TG, LDL-C, LEP, PRL, DHEAS and TT and negative correlations with HDL-C, APN, LH, FSH and E2 in PCOS patients with normal BMI. Multiple linear regression analysis showed that LH, FSH and E2 negatively affected HOMA-IR, while PRL positively affected HOMA-IR. Conclusion There were strong correlations of HOMA-IR in PCOS patients with normal BMI with APN, LEP, and reproductive endocrine hormones. Besides, LH, FSH, E2 and PRL expression had an important effect on IR in normal BMI PCOS patients, which provided a theoretical basis for the exploration of pathogenic mechanisms in normal BMI PCOS patients.

Gender differences in the association between the uric acid to high-density lipoprotein cholesterol ratio and diabetes risk: a mediation analysis of c-reactive protein, triglycerides, and insulin resistance

BackgroundThe uric acid to high-density lipoprotein cholesterol ratio (UHR) has emerged as a novel metabolic marker and is proven to be associated with diabetes risk. However, there is still a lack of systematic research regarding its role in gender differences and underlying mechanisms. This study aims to assess the association of UHR with diabetes risk in the context of gender differences and to investigate its mediation effects through metabolic and inflammatory pathways.MethodsThis study utilized data from NHANES 2005–2010 and included 6,843 adult participants. Multivariate logistic regression was employed to assess the association between UHR and diabetes risk, and restricted cubic spline (RCS) along with correlation analysis was applied to explore its relationship with metabolic risk factors. Multiple mediation analysis was conducted to evaluate the mediating effects of homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and C-reactive protein (CRP) on the association between UHR and diabetes risk.ResultsIn the overall population, UHR was significantly positively associated with diabetes risk, but gender-stratified analysis revealed a stronger predictive effect in women. In the unadjusted model, every unit increase in UHR was linked to an 18.6% increase in diabetes risk in women (p < 0.001). In the quartile analysis, women in the highest quartile showed an 8.49-fold increased risk of diabetes (OR = 8.494, 95% CI: 5.542–13.019, p < 0.001), whereas no significant association was observed in men (p > 0.05). Mediation analysis revealed that HOMA-IR was the main mediator of the relationship between UHR and diabetes risk, with mediation effects of 64.55%, 118.38%, and 39.09% in the overall population, men, and women, respectively. Additionally, the mediation effect of TG was stronger in men (36.78%) and weaker in women (17.31%). The mediation effect of CRP was relatively minimal across all groups, accounting for 7.62% in men and 2.67% in women.ConclusionThis study demonstrates that the association between UHR and diabetes risk exhibits gender differences, with higher diabetes risk observed in women, while men show stronger mediation effects in insulin resistance, lipid metabolism, and inflammatory response.

Waist-to-height ratio and body roundness index: superior predictors of insulin resistance in Chinese adults and take gender and age into consideration

Background and objectivesMetabolic disease has become a global health concern, and insulin resistance (IR) is a crucial underlying mechanism in various metabolic diseases. This study aims to compare the ability of seven anthropometric indicators in predicting IR in the Chinese population, and to find more sensitive and simple anthropometric indicator for early identification of IR.MethodsThis prospective cross-sectional study obtained participants’ medical history, anthropometric indicators, and serum samples from three hospitals in China. Various anthropometric indicators were calculated, including body mass index (BMI), Waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), conicity index (CI), A Body Shape Index (ABSI), body roundness index (BRI), abdominal volume index (AVI). The evaluation of IR is performed using the homeostasis model assessment-insulin resistance (HOMA-IR). Logistic regression analysis examined the relationship between indicators and HOMA-IR. The ability of the anthropometric indicators to predict IR was analyzed using the receiver operating characteristic (ROC) curve. Additionally, a stratified analysis was performed to evaluate the ability of the indicators in different age and gender groups.ResultsThe study included 1,592 adult subjects, with 531 in the non-IR group and 1,061 in the IR group. After adjusting for confounding factors, the anthropometric indicators showed a positive correlation with IR in the general population and across different genders and age groups (OR &amp;gt; 1, p &amp;lt; 0.05), except for ABSI. In the ROC curve analysis, WtHR and BRI had the highest AUC values of 0.711 for detecting IR. The optimal cut-off value for WtHR to diagnose IR was 0.53, while for BRI, it was 4.00. In the gender-stratified and age-stratified analysis, BMI, WtHR, BRI, and AVI all had AUC values &amp;gt;0.700 in females and individuals below 60.ConclusionWtHR and BRI demonstrated a better ability to predict IR in the overall study population, making them preferred indicators for screening IR, and gender and age are important considerations. In the stratified analysis of different genders or age, BMI, WtHR, BRI, and AVI are also suitable for detecting IR in women or individuals under 60 years old in this study.Clinical trial registrationwww.chictr.org.cn, ChiCTR2100054654.

Insulin resistance in childhood obesity: The role of dietary habits and their association with novel markers of cardiovascular disease

Background Childhood obesity presents numerous comorbidities such as insulin resistance (IR) and dyslipidemia, and could be associated with alterations in novel markers of cardiovascular (CV) risk like: (1) the activities of associated enzymes such as lipoprotein associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON 1), (2) reverse cholesterol transport (RCT), which comprises cellular cholesterol efflux (CCE), in addition to lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities, and (3) high density lipoprotein (HDL) antioxidant capacity. Moreover, IR could worsen these cardiometabolic alterations. The objective of the present study was to characterize the effect of IR on novel CV markers in a pediatric population with obesity. Methods Twenty-five obese children and adolescents with IR, and 25 without IR took part in the study. Anthropometric parameters, Tanner stage and dietary habits were registered. Glucose, insulin, non-esterified fatty acid (NEFA), lipid, and high sensitivity C reactive protein (hsCRP) levels, plus Lp-PLA2, LCAT, CETP and PON 1 activities, as well as CCE and HDL antioxidant capacity were measured. A cutoff point of 3.16 in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) determined the presence of IR. Results No differences were observed in age, sex and Tanner stage. Expectedly, the group with IR displayed higher insulin and NEFA levels (p &lt; 0.05). They also presented increased Lp-PLA2 and decreased PON activities (p &lt; 0.05). Importantly, these differences were associated with dietary habits (p &lt; 0.05). Conclusion IR present in pediatric obesity associated with vascular specific inflammation and reduced PON 1 activity, in addition to alterations in glucose metabolism, thus increasing CV risk in adulthood. These proatherogenic disturbances were conditioned by dietary habits.

The effect of a new developed synbiotic yogurt consumption on metabolic syndrome components in adults with metabolic syndrome: a randomized controlled clinical trial

BackgroundStudies have proposed that probiotic intake may ameliorate some of the clinical components of metabolic syndrome (MetS). This study aimed to determine the effects of a new developed synbiotic yogurt containing Lactobacillus plantarum, Lactobacillus pentosus, and Chloromyces marcosianos yeast on the components of MetS in adults with MetS.MethodsIn this randomized, placebo-controlled, clinical trial, 44 participants were divided into two groups to receive 300 grams of synbiotic yogurt or regular yogurt daily for 12 weeks. Anthropometric measurements, blood pressure, and biochemical parameters evaluated before and after the intervention.ResultsDaily consumption of synbiotic yogurt containing L. plantarum, L. pentosus, and C. marcosianos yeast in adults with MetS caused a significant decrease in the levels of fasting blood glucose (FBG) (p = 0.005), fasting insulin (p = 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), waist to hip ratio (WHR) (p = 0.02) and systolic blood pressure (p = 0.008) in the intervention group compared to the control group.ConclusionsAccording to the findings of this study, daily consumption of the synbiotic yogurt was associated with improvements in insulin resistance, systolic blood pressure and WHR, which could be beneficial in patients with MetS.

Cross-Sectional Analysis of Hypoxia-Regulated miRNA-181a, miRNA-199a, HIF-1α, and SIRT1 in the Development of Type 2 Diabetes in Patients with Obstructive Sleep Apnea—Preliminary Study

Introduction: Obstructive sleep apnea (OSA) is recognized as an independent risk factor for diabetes mellitus type 2 (T2DM) development, which is twice as common in patients with OSA compared to non-OSA patients. Objectives: This study aimed to investigate changes in oxygen metabolism and their role in T2DM development among OSA patients through epigenetic processes via miRNA-181a, miRNA-199a, and enzymatic processes via SIRT1 and HIF-1α. Methods: Based on polysomnography, apnea–hypopnea index and the presence of T2DM patients were divided into three groups: control group (n = 17), OSA group (n = 11), OSA&amp;T2DM (n = 20) group. Total RNA was extracted from the buffy coat. Moreover, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) was counted. Results: Morning miRNA-181a expression was significantly higher in the OSA&amp;T2DM group than in the control group: 67.618 vs. 32.685 (p = 0.036). Evening miRNA-199a expression was significantly higher in the OSA group than in the control group: 5.043 vs. 2.081 (p = 0.042), while its morning expression was significantly higher in the OSA&amp;T2DM group when compared to the control: 4.065 vs. 1.605 (p = 0.036). MiRNA-181a evening expression revealed a negative correlation with the SIRT1 evening and morning expressions (R = −0.367, p = 0.010 and R = −0.405, p = 0.004, respectively). Moreover, morning miRNA-181a was positively correlated with HOMA-IR (R = 0.321, p = 0.034). MiRNA-199a evening expression presented a moderate positive correlation with the SIRT1 morning expressions (R = 0.48, p &lt; 0.001) and HOMA-IR (R = 0.35, p = 0.02). Conclusions: Patients suffering from OSA and T2DM had an increased expression of miRNA-181a. Moreover, a negative correlation between miRNA-181a and SIRT1 expression was observed, while a correlation between miRNA-181a and insulin resistance was positive. This phenomenon might suggest a possible epigenetic pathway for an increased incidence of T2DM in OSA patients however further research is needed.

Evaluation of endocrine changes and insulin release in patients with hereditary spherocytosis.

To evaluate endocrinological changes and insulin secretion in patients with hereditary spherocytosis (HS). The study included 30 patients with HS and 30 healthy control groups who were of similar age and gender. Routine tests, including hemogram, biochemical and hormonal tests were conducted on both patients with HS and the control group. HOMA-IR (Homeostasis Model Assessment for Insulin Resistance) and HOMA-ß% (Homeostasis Model Assessment for ß-cell function) values of all cases were also calculated using fasting insulin and fasting glucose values. Among the patient group, 7 patients (23.3%) had short stature, 16 patients (53.3%) had vitamin D deficiency, 1 patient (3.3%) had impaired glucose tolerance, 1 patient (3.3%) had subclinical hypothyroidism, 23 patients (76.6%) had dyslipidemia and 2 patients (6.6%) had growth hormone deficiency. The insulin value in the patient group was 4.0 ± 2.7 mlU/mL and significantly lower than the control group with an insulin value of 9.1 ± 3.9 mlU/mL (P < 0.001). Moreover, glucose (P = 0.036), HOMA-IR (P < 0.001), HOMA-beta (P < 0.001) and C-peptide (P = 0.001) values of the patient group were significantly lower than the control group. The cholesterol (P < 0.001), HDL (P < 0.001) and LDL (P < 0.001) values of the patient group were found to be significantly lower than the control group. We found that insulin secretion decreased in patients with HS and hypocholesterolemia occurred due to chronic hemolysis. More research is needed to elucidate the pathophysiology of decreased insulin secretion seen in HS patients.

Metabolic, genetic and immunological features of relatives of type 1 diabetes patients with elevated insulin resistance.

Insulin resistance plays a pivotal role in the preclinical stages of type 1 diabetes (T1D). This study aims at exploring the genetic, metabolic, and immunological features associated with insulin resistance among individuals at risk of developing T1D. We retrospectively selected relatives of individuals with T1D from participants in the TrialNet Pathway to Prevention study. They were categorized into two groups: high-H (n = 27) and low-H (n = 30), based on the upper and lower quartiles of insulin resistance assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Genetic predisposition was determined using the T1D Genetic Risk Score 1 (GRS1). Additionally, glucose control was evaluated through an oral glucose tolerance test and levels of metabolic hormones and inflammatory cytokines were measured in the serum. Flow cytometry analysis was employed to assess frequency and phenotype of islet-specific CD8 T cells. While GRS1 were similar between the low-H and high-H groups, high-H individuals displayed a distinct metabolic profile, characterized by compensatory hyperinsulinemia, even while maintaining normoglycemia. Circulating cytokine levels were similar between the two groups. However, immune profiling revealed a central memory and activated profile of GAD65-specific CD8 T cells, along with an increased frequency of insulin-specific CD8 T cells in high-H individuals. The enrichment in insulin-specific CD8 T cells was independent of body mass. These findings highlight the intricate interplay between insulin resistance, genetic factors, and immune activation in the context of T1D susceptibility, indicating potential connections between insulin resistance and immune responses specific to islet cells.

The waist-to-height ratio is a good predictor for insulin resistance in women with polycystic ovary syndrome

ObjectiveThis study aimed to explore the role of the waist-to-height ratio (WHtR) in assessing insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS).Materials and methodsWe enrolled 882 PCOS-afflicted women in a cross-sectional analysis to evaluate the association of the WHtR with IR. Their demographic characteristics, anthropometric parameters, and fasting blood samples were collected and measured. Moreover, IR was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR). We estimated the relationship between the WHtR and IR and the cut-off thresholds of the WHtR for IR using multivariable linear regression and logistic regression models, respectively.Result(s)The prevalence rate of IR was 51.9%. The patients with PCOS and IR displayed significantly increased values for body mass index (BMI), waist circumference (WC), WHtR, systolic blood pressure (SBP), diastolic blood pressure (DBP), free androgen index (FAI), HOMA-IR, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB). However, the patients with PCOS and IR showed a reduction in estradiol (E2), luteinizing hormone (LH), LH/FSH ratio, sex hormone binding globulin (SHBG), and high-density lipoprotein (HDL-C) values than those without IR. Moreover, BMI (log-transformed), WC, and HOMA-IR (log-transformed) were positively correlated with the WHtR. When adjusting for potential confounding variables, the WHtR was significantly associated with HOMA-IR (log-transformed), with a standardized regression coefficient of 0.271. Furthermore, the WHtR was significantly associated with an increased risk of IR, with the adjusted odds ratio (OR) of 3.15 (WHtR multiplied by 10). Additionally, the WHtR helped to identify IR in women with PCOS with an optimal cut-off point of 0.519 (Youden index = 0.433).Conclusion(s)The WHtR had a positive association with IR in women with PCOS. Hence, we suggest that the WHtR, as a simple, practical, and reliable anthropometric measure, can be used to predict the risk of IR in patients with PCOS.

The impact of metabolic health on fibromyalgia: insights from insulin resistance and related indexes

ABSTRACT Objectives To assess the association between fibromyalgia (FM) and insulin resistance (IR) using multiple IR indices in FM patients and to investigate how these indices vary with the severity of FM. Methods This cross-sectional study included 70 female patients diagnosed with FM and 70 age-matched female healthy controls. The data collected included demographics, clinical characteristics, and laboratory parameters. FM severity was evaluated using the Fibromyalgia Impact Questionnaire-Revised (FIQR). The metabolic indices calculated were the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI), triglyceride – glucose index (TyG), triglyceride to HDL cholesterol ratio (TG/HDL-C), and Metabolic Score for Insulin Resistance (METS-IR). Results FM patients exhibited significantly higher HOMA-IR values (p = 0.002), and lower QUICKI values (p = 0.000) than controls. METS-IR also showed significant differences between FM patients and controls (p = 0.026). HOMA-IR and METS-IR values increased with FM severity, whereas QUICKI values decreased (p < 0.05). Duration of FM showed a moderately positive correlation with HOMA-IR (r = 0.249, p = 0.027). For TG/HDL-C and METS-IR, the correlations were weaker, but still positive (r = 0.094, p = 0.378, and r = 0.184, p = 0.056, respectively). Conclusion This study observed a significant association between FM and IR, as evidenced by metabolic indices in FM patients compared to controls. IR levels tended to increase with FM severity and duration. These findings suggest that IR could play a role in FM pathogenesis. Non-invasive and practical methods, such as METS-IR, may provide advantages for metabolic screening in FM patients; however, further studies are needed to establish their clinical utility.

Lack of correlation between asprosin serum levels and hyperphagic behavior in subjects with prader-Willi Syndrome.

Individuals with Prader-Willi syndrome (PWS) exhibit hyperphagic behavior, the severity of which varies throughout life. The mechanisms underlying this behavior are still unknown. Asprosin is a new discovered adipokine involved in the regulation of food intake, glucose homeostasis and energy balance. In this study we assessed asprosin serum levels in a cohort of children, adolescents and adults with PWS with the aim to correlate them with hyperphagic behavior, body mass index (BMI) and metabolic parameters, and to evaluate age-related changes. This cross-sectional study included 87 children and adolescents and 31 adults with PWS. Auxological data, fasting levels of glucose, insulin, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG) and asprosin were collected, and the homeostasis model assessment for insulin resistance (HOMA-IR) was determined. The 11-item Italian version of the Hyperphagia Questionnaire (HQ) was administered to the parents/caregivers of the patients to assess hyperphagia. Patients were analysed according to age (children < 10 years, adolescents between 10 and 17.9 years, adults ≥ 18 years) or BMI categories [normal weight (NW), overweight (OW), and obesity (OB)]. No significant correlations were found between asprosin levels and cardiometabolic risk factors in the whole cohort. Higher values of asprosin were found in adults compared with adolescents, as well as in the OB group compared to the NW group (p = 0.014). Hyperphagia total score and hyperphagic subdimensions were significantly lower in children compared to adults (p < 0.05). Similarly, hyperphagia total score and hyperphagic subdimensions were significantly lower in the NW group compared to the OB group. Asprosin levels were significantly higher in patients with deletion versus patients with uniparental disomy (p = 0.037). By logistic regression analysis, HQ total score and hyperphagic subdimensions were significantly associated with BMI-SDS independently of age, sex, and asprosin levels. In conclusion, our data demonstrated higher asprosin levels in PWS individuals with OB compared to NW, while differences by age and sex were inconsistent. The lower levels of hyperphagia, BMI-SDS, and metabolic variables in children with PWS compared to adults underline that prevention of obesity should start very early in life and should be maintained over time.

The potential of insulin resistance indices to predict non-alcoholic fatty liver disease in patients with type 2 diabetes

BackgroundThe triglyceride-glucose (TyG) index and related parameters, as well as the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), have been developed as insulin resistance markers to identify individuals at risk for non-alcoholic fatty liver disease (NAFLD). However, its use for predicting NAFLD in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this study, we aimed to observe the performance of insulin resistance indices in diagnosing NAFLD combined with T2DM and to compare their diagnostic values in clinical practice.Patients and methodsOverall, 268 patients with T2DM from the Endocrinology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine were enrolled in this study and divided into two groups: an NAFLD group (T2DM with NAFLD) and a T2DM group (T2DM without NAFLD). General information and blood indicators of the participants were collected, and insulin resistance indices were calculated based on these data. Receiver operating characteristic (ROC) analysis was conducted to calculate the area under the curve (AUC) for insulin resistance-related indices, aiming to assess their ability to discriminate between T2DM patients with and without NAFLD.ResultsROC analysis revealed that among the five insulin resistance-related indices, four parameters (TyG, TyG-body mass index [BMI], TyG-waist circumference [WC], and TyG- (waist–hip ratio [WHR]) exhibited high predictive performance for identifying NAFLD, except for HOMA-IR (AUCs:0.710,0.738,0.737 and 0.730, respectivly). TyG-BMI demonstrated superior predictive value, especially in males. For males, the AUC for TyG-BMI was 0.764 (95% confidence interval [CI] 0.691–0.827). The sensitivity and specificity for male NAFLD were 90.32% and 47.89%, respectively. Moreover, in the Generalized linear regression models, there were positive associations of TyG, TyG-BMI, TyG-WC, TyG-WHR, and HOMA-IR with controlled attenuation parameter (CAP), with β values of 21.30, 0.745, 0.247, and 2.549 (all P < 0.001), respectively.ConclusionTyG-BMI is a promising predictor of NAFLD combined with T2DM, particularly in lean male patients.

ApoC-III proteoforms are associated with better lipid, inflammatory, and glucose profiles independent of total apoC-III

BackgroundApolipoprotein (apo) C-III is involved in several processes that increase triglyceride levels, inflammation, and insulin resistance. Four of its proteoforms have been the focus of several studies and have shown differential associations with cardiovascular risk biomarkers, mostly lipids. However, there are other proteoforms of apoC-III that have not yet been investigated in detail. The aim of this study was to evaluate the associations of seven apoC-III proteoforms with a comprehensive set of biomarkers, including lipid metabolism, inflammation, and glucose homeostasis.MethodsSeven apoC-III proteoforms (apoC-III0a, apoC-III0b, apoC-III1, apoC-III1d, apoC-III2, apoC-III2d, and apoC-III0f) were measured using a mass spectrometry immunoassay in 875 participants from the cross-sectional study of the Di@bet.es cohort. The complete lipoprotein profile was obtained via the Liposcale test, and the proton nuclear magnetic resonance (1H-NMR)-assessed glycoprotein signals were also obtained as biomarkers of inflammation.ResultsThree proteoform ratios (apoC-III2d, apoC-III2, and apoC-III0f normalized to apoC-III1) showed protective associations with most of the cardiovascular risk biomarkers in comparison with total apoC-III in linear regression models and were negatively associated with triglycerides (β=-0.173, p < 0.001; β=-0.297, p < 0.001; β=-0.223, p = 0.002), very low-density (VLDL) particle concentration (β=-0.133, p < 0.001; β=-0.265, p < 0.001; β=-0.203, p < 0.001), GlycA (β=-0.148, p < 0.001; β=-0.263, p < 0.001; β=-0.211, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (β=-0.096, p = 0.003; β=-0.199, p < 0.001; β=-0.114, p = 0.002). These associations were partly independent of total apoC-III concentrations. Participants with high levels of these proteoforms had a lower prevalence of cardiometabolic disorders, such as type 2 diabetes (p = 0.022), obesity (p = 0.001), and metabolic syndrome (p = 0.013).ConclusionsWhile apoC-III is positively associated with biomarkers of cardiometabolic risk, the proportions of three apoC-III proteoforms show opposite associations, independent of total apoC-III concentrations. Measuring not only apoC-III but also the proportions of apoC-III proteoforms can provide valuable information since individuals with similar levels of total apoC-III could display opposite lipid profiles depending on the proportion of apoC-III proteoforms.Graphical abstract

Bariatric Surgery-Induced Weight Loss Reduces CD36 Expression in Association with the Improvement of Insulin Resistance in Monocytes of Obese Subjects

Obesity is often associated with oxidative stress and lipid peroxidation, which are known risk factors for insulin resistance and type 2 diabetes. Cell differentiating-36 (CD36) is a cell membrane receptor that is also implicated in early stages of insulin resistance and diabetes due to its ability to bind and internalize oxidatively modified low-density lipoprotein (oxLDL). Bariatric surgery is an effective procedure that induces substantial weight loss and improves obesity-associated comorbidities. This study investigated the effect of Roux-en-Y Gastric Bypass Surgery (RYGB) on plasma oxLDL and CD36 expression and assessed possible link with insulin activity.Th study was conducted prospectively in thirty-six obese subjects who underwent RYGB. Weight loss was recorded before and at 6 and 12 months postoperatively. The expression of CD36 in monocytes was analyzed by flow cytometry and polymerase chain reaction (PCR). The concentrations of blood lipids, glucose, insulin and oxLDL were assayed in plasma, and the homeostatic model assessment insulin resistance index (HOMA-IR) was determined.There was a significant reduction of monocyte CD36 levels at 6 months (-48%) and 12 months (-63%) post-surgery. The concentrations of plasma insulin, oxLDL and triglycerides were reduced after 6 months (-38%, -41% and -29%, respectively) and after 12 months (-51%, -61% and -36%, respectively) post-surgery. The level of monocyte CD36 was positively correlated with body mass index (BMI), blood insulin and HOMA-IR.The reduction of monocyte CD36 expression and plasma oxLDL level following RYGB-induced weight loss may contribute to the improvement of insulin resistance cardiovascular disease risk factors.

The role of telomere shortening in ambient ozone exposure-related insulin resistance

BackgroundOzone (O3) exposure and telomere shortening are associated with insulin resistance (IR). However, the role of telomere shortening in ambient O3 exposure-related IR is largely unclear. MethodsThe Henan Rural Cohort recruited participants and performed a random forest method to estimate residential O3 concentration. IR was reflected by homeostasis model assessment-IR, quantitative insulin sensitivity check index, triglyceride and glucose index, etc. Generalized linear model, quantile regression model, and mediation effects analysis were utilized to assess the associations of O3 exposure and relative telomere length (RTL) with longitudinal IR markers and their change rates. Furthermore, the role of telomere homeostasis in O3-exposure-induced IR in vivo and in vitro experiments was verified. ResultsO3 exposure was positively associated with longitudinal IR. The proportions of RTL mediated associations between O3 exposure and longitudinal IR markers ranged from 11.92% to 60.36%. O3-exposed mice exhibited a higher glucose load, upregulation of GSK-3β and G-6-Pase expression at mRNA levels, glycogen accumulation reduction, telomere shortening, and decreased telomerase reverse transcriptase activity relative to air-exposed mice. In vitro experiments reveal that overexpression of TERT in HepG2 cells up-regulated G-6-Pase mRNA expression level. ConclusionsImpaired telomere homeostasis may be involved in O3 exposure-related IR via inhibition of glycogen synthesis and acceleration of gluconeogenesis and the specific mechanisms are still further elucidated.

Association of insulin resistance with chronic kidney disease in individuals without diabetes in a community population in South China

BackgroundTo explore the relationship of insulin resistance (IR) with chronic kidney disease (CKD) in individuals without diabetes.MethodsWe performed a cross-sectional survey among 2142 community-based participants without diabetes from southern China from June to October 2012 and excluded the incomplete data. We divided all the participants into four groups according to the quartiles of homeostasis model assessment of IR (HOMA-IR). Logistic regression models were used to explore the associations of IR with CKD in these subjects.ResultsIn the unadjusted model, compared with the quartile one group, IR was significantly associated with CKD (odds ratio [OR] = 2.24, P < 0.001; OR = 4.46, P < 0.001) in the quartile three and four groups, and the association was still significant (OR = 2.08, P = 0.005; OR = 3.89, P < 0.001 ) after adjusting for potential confounders (including age, current smoker, current alcohol use, physical inactivity, education level, systolic blood pressure, diastolic blood pressure, serum triglyceride, and body mass index). The area under the receiver operating characteristic curve (95% confidence interval) of HOMA-IR for diagnosing CKD was 0.67 (0.64, 0.71). The cut-off value was 2.5, the sensitivity was 75.2%, and the specificity was 56.4%.ConclusionsIR is associated with Chronic Kidney Disease (CKD) in participants without diabetes. It has been proposed that CKD patients may benefit from reducing their insulin resistance.

The association between triglyceride glucose index and the risk of cardiovascular disease in obstructive sleep apnea

PurposeThe triglyceride glucose (TyG) index is a dependable indicator of insulin resistance (IR), serves as a valuable biomarker for identifying obstructive sleep apnea (OSA) and predicting its comorbidities. Both OSA and the TyG index are significantly related to the incidence and development of cardiovascular disease (CVD). We focus on investigating the relationship between the TyG index and the incidence of CVD risk in OSA.MethodsThe TyG index, homeostatic model assessment of IR (HOMA-IR) index, and polysomnography were assessed in 191 participants with OSA and without pre-existing CVD. To estimate the lifetime CVD risk, we employed the ‘Prediction for Atherosclerotic CVD Risk in China’ equation. The TyG index’s association with CVD risk was scrutinized using multivariable logistic regression models, contrasting it with the HOMA-IR index. We compared the predictive power for high lifetime CVD risk of the TyG index and the HOMA-IR index using receiver-operating characteristic (ROC) curve analysis.ResultsA total of 89 participants had high lifetime CVD risk. In fully adjusted model and additionally adjusted for HOMA-IR index, participants situated within the fifth quantile of the TyG index exhibited an increased lifetime CVD risk, with OR of 4.32 (95% CI, 1.19–15.67). The TyG index demonstrated significant predictive power for high lifetime CVD risk across varying severities of OSA and outperformed the HOMA-IR index, as evidenced by a larger area under the ROC curve.ConclusionThe TyG index, independent of the HOMA-IR index and obesity, was linked to an increased lifetime CVD risk. In predicting cardiovascular outcomes, the TyG index could potentially outperform the HOMA-IR index among individuals with OSA.

The effect of probiotics on gestational diabetes mellitus: an umbrella meta-analysis

BackgroundPrior studies indicated the positive effects of probiotics on glycemic regulation in patients with gestational diabetes mellitus (GDM). Nonetheless, the results remain inconclusive. To address this, we conducted an umbrella meta-analysis to evaluate the impact of probiotics on glycemic indicators in GDM.MethodsA comprehensive search was conducted on the PubMed and Scopus databases to identify all relevant meta-analyses of randomized clinical trials published until July 2024. The outcomes included serum hemoglobin A1C (HbA1c), fasting blood insulin (FBI), fasting blood sugar (FBS), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), homeostatic model assessment of beta cell function (HOMA-B), C-peptide, and oral glucose tolerance test (OGTT). Standardized mean difference (SMD) was used to test the effects.ResultsIn total, 27 studies, comprising 33,378 participants, were included in the analysis. Probiotics resulted in a significant decrease in FBS (SMD: -0.39, 95% CI: -0.56 to -0.23), especially when administered for ≤ 7 weeks. Significant reductions were also observed in FBI (SMD: -1.99, 95% CI: -2.41 to -1.58), HOMA-IR (SMD: -0.61, 95% CI: -0.72 to -0.50), and HOMA-B (SMD: -24.58, 95% CI: -30.59 to -18.56). Moreover, supplementation with probiotics significantly improved QUICKI (SMD: 0.007, 95% CI: 0.004 to 0.01). There was significant evidence of heterogeneity and publication bias. No significant effects were observed on 1-h OGTT, 2-h OGTT, HbA1c, and C-peptide. No dose-specific effect was observed.ConclusionsSupplementation with probiotics could improve glycemic control in women with GDM. The effects of probiotics on HOMA-IR, HOMA-B, and fasting insulin were clinically important, while, their effect on FBS was not clinically important.

Endoscopic indicators of insulin resistance: associations with erosive esophagitis and regular arrangement of collecting venules (RAC).

Insulin resistance is a key factor in metabolic syndrome. Identifying indicators of insulin resistance through endoscopic findings could be valuable in assessing a patient's systemic metabolic status. Thus, we conducted a retrospective study to investigate the association between endoscopic findings and insulin resistance. We reviewed 1,070 patients who underwent screening endoscopy with a rapid urease test at Bundang Jesaeng General Hospital from February 2023 to June 2023. Patients were classified based on insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMAIR). Propensity score matching was performed to adjust for baseline characteristics. After matching, 420 patients without insulin resistance and 210 with insulin resistance were selected. Endoscopic findings showed a significant association between insulin resistance and the presence of erosive esophagitis (p = 0.040). Furthermore, the severity of erosive esophagitis was positively correlated with the degree of insulin resistance, as indicated by an increased HOMAIR. Multivariate analysis showed that erosive esophagitis significantly increased the risk of insulin resistance, while the presence of regular arrangement of collecting venules (RAC) was associated with a lower risk of insulin resistance. Insulin resistance is significantly associated with specific endoscopic findings, particularly erosive esophagitis and the absence of RAC, suggesting associations that may be useful in guiding further research into endoscopic indicators of metabolic complications. Moreover, we observed a proportional relationship between the severity of erosive esophagitis and the degree of insulin resistance. Further research is needed to explore these associations.

Metformin effectively alleviates the symptoms of Alzheimer in rats by lowering amyloid β deposition and enhancing the insulin signal

Alzheimer’s disease (AD) exhibits distinct biochemical and histopathological attributes, encompassing cellular, neuronal, and oxidative impairment. There is also an abnormal buildup, misfolding and clumping of amyloid β (Aβ). The present study aimed to explore the influence of the antihyperglycemic agent metformin on rats with AD-like symptoms, while also elucidating the intricate relationship between insulin resistance and AD. The rats were categorized into five groups: a control group, a saline-administered group, a metformin-treated group, AD-model rats, and AD-rats treated with a 200 mg/kg dose of metformin. Cognitive impairment was rated using the classical labyrinth test. Moreover, serum biochemical parameters, encompassing glucose levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Glycated hemoglobin (HbA1c), lipid profile, kidney, and liver function, were evaluated. Additionally, oxidative, antioxidant, and neurotransmitter parameters were measured in hippocampus tissues. Also, the Aβ and insulin receptor substrate 2 (IRS-2) were measured by immunoblotting. Besides hippocampal histopathology, glial fibrillary acidic protein (GFAP) and calretinin immunoreactivity were monitored. The study findings disclosed deficits in memory and learning capabilities among AD rats. Furthermore, AD-afflicted rats exhibited heightened glucose levels, elevated HOMA-IR and HbA1c values, alongside compromised liver, and kidney functions. Additionally, an upsurge in oxidative stress coincided with a notable reduction in the antioxidant system and neurotransmitters activities. The levels of Aβ deposition increased, while IRS-2 expression subsided, accompanied by alterations in the hippocampal structure and neuronal damage. These changes were paralleled by an intensification in GFAP reactivity and a detracting in calretinin reactivity. Metformin was altogether able to move forward cognitive execution by means of bringing down oxidative stress and Aβ conglomeration. Furthermore, metformin was able to improve neurotransmitters and insulin signals. AD, glucose impairment, and brain insulin resistance are completely interlinked, and future AD medications may be inspired by diabetic medication.