Surrogate Of Insulin Resistance Research Articles

Association between different insulin resistance surrogates and osteoarthritis: a cross-sectional study from NHANES 1999-2018.

Previous studies have demonstrated a relationship between prevalence of Osteoarthritis (OA) and insulin resistance (IR). The correlation between IR surrogates indices and gold standard tool for IR evaluation (Hyperinsulinemic-euglycemic clamp (HIEC)) have been well demonstrated. However, few studies evaluated the relationship between IR surrogates and OA. The aim of this study is to investigate the potential associations between different IR surrogates (the homeostatic model assessment of insulin resistance (HOMA-IR) index, the triglyceride glucose (TyG) index, the triglyceride glucose with body mass (TyG-BMI) index, the triglyceride glucose with waist circumference (TyG-WC) index, and the triglyceride glucose with the ratio of waist circumference divided by height (TyG-WtHR) index) and OA. This study used data from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analysis was used to assess the associations of different IR surrogates with OA. After adjusting for covariates, TyG-BMI index (OR = 1.006, 95% CI [1.004, 1.007], P < 0.0001), TyG-WC index (OR = 1.002, 95% CI [1.002, 1.003], P < 0.0001) and TyG-WtHR index (OR = 1.425, 95%CI [1.292,1.572], P < 0.0001) still showed robust positive correlation with IR. The risk of OA in the fourth quartile of the TyG-BMI index, TyG-WC index, and TyG-WtHR index are 2.634-fold, 2.651-fold, and 2.433-fold higher than that in the first quartile, respectively. Compared to the HOMA-IR index and the TyG index, the association between the TyG-BMI, TyG-WC, and TyG-WtHR indices and OA is closer and more stable. The TyG-WtHR index has the highest accuracy in predicting OA, followed by the TyG-WC and TyG-BMI index.

Associations of four surrogate insulin resistance indexes with non-alcoholic steatohepatitis in Chinese patients with obesity: a cross-sectional study.

This study was designed to evaluate the association of four surrogate indexes of IR with NASH in patients with obesity. A total of 270 patients who underwent bariatric surgery, were included in this cross-sectional study. NASH was diagnosed based on liver biopsies. Binary logistics regression analyses were performed to assess the associations of four surrogate indexes of IR (HOMA-IR, Matsuda index, TyG, and TG/HDL-C) with NASH in patients with obesity. The restricted cubic spline was used to assess the dose-response associations of surrogate indexes of IR with NASH after adjusting for confounding factors. NASH was diagnosed in 136 patients, with a prevalence of 50.37%. Compared with tertile 1, the fully adjusted ORs (95% CIs) of NASH for tertile 3 were 2.711(1.113-6.608) and 0.297 (0.152-0.579) for TyG and Matsuda index. Consistently, per SD increment of TyG were still significantly associated with 64% increased risks of NASH, and per SD increment of Matsuda index were still significantly associated with 38% decreased risks of NASH. In contrast, no significant associations were found between HOMA-IR and TG/HDL-C and the risk of NASH in patients with obesity (all P > 0.05). After adjusting covariates in restricted cubic splines, the risk of NASH decreased with the increment of Matsuda Index levels (P-nonlinear = 0.442, P-overall = 0.007) and with the decrement of TyG levels (P-nonlinear = 0.004, P-overall = 0.001). In patients with obesity, TyG and Matsuda index were independently related to the risk of NASH after adjustment for traditional risk factors. In addition, compared with HOMA-IR and TG/HDL-C, the Matsuda index and TyG may be more suitable for NASH prediction in patients with obesity.

Insulin resistance and sarcopenia: a prognostic longitudinal link to stroke risk in middle-aged and elderly Chinese population

BackgroundStroke is the leading cause of death in middle-aged and elderly people in China. Insulin resistance (IR) and sarcopenia are both closely associated with metabolic diseases. However, the relationship between these two indicators and stroke has not been fully investigated. The aim of this study was to investigate the relationship between IR and sarcopenia and the risk of new-onset stroke.MethodsUsing longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, Cox proportional hazards models were used to determine the association between IR surrogate indicators and sarcopenia status with stroke incidence.ResultsIn the present study, during a median 7 years of follow-up, we included 7009 middle-aged and elderly residents, of whom 515 presented with stroke incidence. After adjustment for potential confounders, both baseline IR surrogates and sarcopenia independently predicted stroke risk. In addition, co-morbidities had a higher risk of stroke than other groups. The positive association between TyG-WC and sarcopenia on stroke risk was particularly significant [HR (95% CI): 2.03 (1.52, 2.70)]. In subgroups of different ages and sexes, the combination of IR and sarcopenia is associated with the highest risk of stroke.ConclusionsWe found that IR and sarcopenia synergistically increase the incidence of stroke in older adults. This finding provides new perspectives for stroke detection and intervention and highlights the importance of early detection and management of IR and sarcopenia in older adults.

Comparison of the predictive value of four insulin resistance surrogates and hyperuricemia in women with recurrent pregnancy loss: A cross-sectional study.

Insulin resistance (IR), hyperuricemia (HUA), and recurrent pregnancy loss (RPL) elevate the risk of cardiovascular disease and metabolic disorders, while also impacting reproductive health. The relationship between IR, HUA, and RPL has not been thoroughly investigated. This study investigates the relationship between four IR surrogates and the risk of HUA in RPL patients. Data from a real-world study on RPL in China were analyzed using multivariable regression to determine the relationship between HUA and triglyceride and glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI), triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and metabolic score for insulin resistance (METS-IR). The predictive ability of these surrogates for detecting HUA in RPL patients was evaluated using the area under the curve and receiver operating characteristic analysis. Sensitivity analysis was performed using bootstrapping resampling. The study included 769 patients with a mean age of 30 ± 4 years old, 8.32% of whom had HUA. Four IR surrogates were closely related to HUA in patients of RPL after adjusting for age, menstrual cycle, creatinine, alanine transaminase, aspartate transaminase, total cholesterol, homocysteine, and low-density lipoprotein, with area under the curve values of TyG index (OR = 0.693, 95% confidence interval [CI]: 0.626, 0.759), TyG-BMI (OR = 0.731 95% CI: 0.657, 0.805), TG/HDL-C (OR = 0.703, 95% CI: 0.641, 0.764), and METS-IR (OR = 0.728, 95% CI: 0.655, 0.799). Bootstrap resampling yielded similar results. The TyG index, TyG-BMI, TG/HDL-c, and METS-IR significantly correlated with HUA in patients with RPL. The TyG-BMI had the highest predictive value of the four IR surrogates.

Incremental value of blood-based markers of liver fibrosis in cardiovascular risk stratification.

Non-alcoholic fatty liver disease (NAFLD) with advanced liver fibrosis is associated with cardiovascular disease (CVD). To examine if markers of vascular injury mediate the link between liver fibrosis non-invasive tests (LFNITs) and CVD events, and to compare the incremental predictive value of LFNITs over established CVD risk scores. Consecutively recruited individuals (n=1,692) with or without clinically overt coronary artery disease (CAD) from the Athens Cardiometabolic Cohort, were analysed. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), and BARD score were evaluated for direct and indirect associations with indices of subclinical arterial injury including carotid maximal wall thickness (maxWT) and pulse wave velocity (PWV) and with a composite of major adverse cardiovascular events (MACE) that consisted of cardiac death, acute myocardial infarction, or coronary revascularization (39-month median follow-up). FIB-4 was the only LFNIT which consistently associated with multiple markers of vascular injury, irrespective of CAD presence and after controlling for traditional risk factors, surrogates of insulin resistance or obesity (adjusted p<0.05 for all). FIB-4 also independently associated with CAD presence (adjusted OR 6.55 (3.48-12.3), p<0.001). Increased FIB-4>2.67 was incrementally associated with increased risk for MACE (OR (95% CI) 2.00(1.12, 3.55), deltaAUC (95% CI) 0.014(0.002-0.026)). These associations were mediated by maxWT rather than PWV. Only FIB-4 (>3.25) was independently and incrementally associated with all-cause mortality (adjusted p<0.05). In a cardio-metabolically diverse population, the incremental associations of LFNITs with CVD outcomes were mediated by atherosclerotic burden rather than arterial stiffening. FIB-4 consistently demonstrated associations with all study endpoints. These findings provide mechanistic insights and support the clinical applicability of FIB-4 in CVD prevention.

Abstract P136: Phosphorylation and regulation of URAT1 by insulin and NaCl: a possible mechanism linking insulin resistance and excessive salt intake to hyperuricemia

Objective: Insulin resistance (IR) is the key environmental factor associated with hyperuricemia; however, the underlying mechanisms are not fully understood. Although several studies suggested that excessive salt intake results in hyperuricemia, the association still remains controversial. Focusing on urate transporter 1 (URAT1), we here investigated the mechanisms by which insulin and salt intake contribute to hyperuricemia. Methods: In a large UK Biobank (UKB) dataset involving 377,358 participants, we evaluated the association of TyG index (a surrogate of IR) and habitual salt intake with serum uric acid levels using multivariable regression models. We addressed whether single nucleotide polymorphisms (SNPs) that influence URAT1 expression (eQTL) modify the association of TyG index with serum uric acid levels. We also analyzed underlying mechanisms by using HEK cells expressing hURAT1. Results: In UKB dataset, TyG index and habitual salt intake were significantly and independently associated with elevated serum uric acid levels (P &lt; 0.05). From previous studies and imputation accuracy, we extracted an eQTL SNP for SLC22A12 gene and found that there is a positive interaction between TyG Index and the eQTL SNP. As post-translational modification is the key mechanism that enables adaptation to environmental changes, we evaluated the contribution of phosphorylation by AGC kinases, such as Akt, as possible downstream effectors of insulin signaling and salt-sensing pathway. Western blotting with phospho-Akt substrate motif antibody confirmed URAT1 phosphorylation and identified T350 and T408 as candidate sites. Among them, URAT1 carrying non-phosphorylatable A408 substitution (T408A-URAT1) suppressed glycosylation and plasma membrane translocation, while T350A had no effect. By using kinase screen assay involving 53 AGC and related Ser/Thr kinases, we found that SGK1, PKA, and PKG also phosphorylated URAT1-T408. Insulin and NaCl loading induced Akt and SGK1 expression respectively, which resulted in URAT1 phosphorylation and increased cell-surface membrane expression; this effect was abolished in T408A-URAT1. Finally, we found that URAT1-T408 phosphorylation was also detected in human kidney sections. Conclusion: IR and excessive salt intake contribute to hyperuricemia, and the effect is in part mediated by hURAT1. Mechanistically, insulin and NaCl promote membrane trafficking of URAT1 by inducing T408 phosphorylation through Akt and SGK1, respectively.

Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank

PurposeThis study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer.MethodsA total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC).ResultsTen years after recruitment, 0.16% (95%CI 0.11–0.26%) had esophageal cancer and 4.17% (95%CI 3.86–4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C.ConclusionTyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification.

Triglyceride-Glucose Index, Modifiable Lifestyle, and Risk of Colorectal Cancer: A Prospective Analysis of the Korean Genome and Epidemiology Study.

Insulin-mediated pathways plausibly explain the pathogenesis of colorectal cancer (CRC). The triglyceride-glucose index (TyG) is a surrogate of insulin resistance (IR), but its association with CRC in the Korean population has not been evaluated. From the 2004-2013 Korean Genome and Epidemiology Study, 98,800 participants aged 40-69 years were followed through 2020. Data on CRC incidence were obtained from the Korean National Cancer Center registry. Cox regression models and restricted cubic splines were fitted to examine the association between the TyG; In [(triglycerides) × (fasting glucose)/2] and CRC incidence. Joint effects of modifiable lifestyle factors and TyG on CRC risk were also investigated. Median follow-up time was 10.6 years, and 699 CRC cases were observed. A unit-increment in TyG was associated with increased risk of CRC combined (hazard ratio, HR: 1.28, and 95% confidence interval, CI: 1.12-1.46), colon (1.29, 1.10-1.54), and rectal cancer (1.24, 1.01-1.52). Associations were dose-dependent, with linear associations observed for CRC and colon, but non-linear associations were observed for rectal cancer. A high TyG index (above 8.4) combined with overweight/obesity was linked to an increased risk of CRC (1.31, 1.07-1.61) and colon cancer (1.33, 1.03-1.72). When combined with low fruit and vegetable intake, the risks were higher for CRC (1.40, 1.12-1.74) and colon cancer (1.57, 1.18-2.09). Combined with high red meat consumption, the risks were elevated for CRC (1.32, 1.05-1.65) and colon cancer (1.52, 1.15-2.02). A high TyG index was associated with a higher risk of colorectal cancer, and the risk was highest among participants with a high BMI, low fruit and vegetable intake, and high intake of red meat, suggesting a role of both insulin resistance and modifiable lifestyle in colorectal cancer development.

Relationship between four insulin resistance surrogates and regression to normoglycemia from prediabetes among Chinese adults: A longitudinal Cohort Study.

We aimed to investigate the association of the triglyceride glucose-body mass index(TyG-BMI), metabolic score for insulin resistance (METS-IR) with regression to normoglycaemia, and further to compare the value of the four insulin resistance(IR) related indices(TyG-BMI, METS-IR, TyG and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio) in identifying regressions to normoglycaemia from prediabetes. A total of 15,025 patients with prediabetes from the DATA-DRYAD database were included. Cox proportional hazards regression models and restricted cubic spline functions were performed to explore the association and nonlinearity between the indices with the incidence rate of normoglycaemia. Sensitivity and subgroup analyses evaluated the robustness of our findings. Compared with the first quintile, TyG-BMI and METS-IR was negatively linked with the probability of regression to normoglycaemia from prediabetes, the adjusted effect size of the highest quintiles of METS-IR were the most obvious (HR:0.456,95% CI:0.4-0.519), followed by TG/HDL (HR:0.792, 95% CI:0.733-0.856), TyG-BMI (HR:0.816, 95% CI:0.73-0.911) and TyG (HR:0.841, 95% CI: 0.754-0.937) (all p for trend <0.001). A 1.0 SD increase in METS-IR induced a 43% decrease in the probability of regression to normoglycaemia, with 9.8% for TyG-BMI. There were nonlinear associations between TyG-BMI and METS-IR and outcomes, with the inflection point of the TyG-BMI being 218.2 and that of the METS-IR being 37. The METS-IR might be the most superior indicator among the four non-insulin indices in identifying regressions to normoglycaemia from prediabetes in clinical application. The inflection points of the METS-IR and TyG-BMI may be instructive therapeutic points for assessing the status of prediabetes in advance and making more appropriate management and health care decisions.

Comparison of Ten Surrogate Insulin Resistance and Obesity Markers to Identify Metabolic Syndrome in Mexican Adults.

Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20-39 and 40-59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20-39 and triglyceride-glucose index (TyG) in those aged 40-59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level.

Which surrogate insulin resistance indices best predict coronary artery disease? A machine learning approach

BackgroundVarious surrogate markers of insulin resistance have been developed, capable of predicting coronary artery disease (CAD) without the need to detect serum insulin. For accurate prediction, they depend only on glucose and lipid profiles, as well as anthropometric features. However, there is still no agreement on the most suitable one for predicting CAD.MethodsWe followed a cohort of 2,000 individuals, ranging in age from 20 to 74, for a duration of 9.9 years. We utilized multivariate Cox proportional hazard models to investigate the association between TyG-index, TyG-BMI, TyG-WC, TG/HDL, plus METS-IR and the occurrence of CAD. The receiver operating curve (ROC) was employed to compare the predictive efficacy of these indices and their corresponding cutoff values for predicting CAD. We also used three distinct embedded feature selection methods: LASSO, Random Forest feature selection, and the Boruta algorithm, to evaluate and compare surrogate markers of insulin resistance in predicting CAD. In addition, we utilized the ceteris paribus profile on the Random Forest model to illustrate how the model’s predictive performance is affected by variations in individual surrogate markers, while keeping all other factors consistent in a diagram.ResultsThe TyG-index was the only surrogate marker of insulin resistance that demonstrated an association with CAD in fully adjusted model (HR: 2.54, CI: 1.34–4.81). The association was more prominent in females. Moreover, it demonstrated the highest area under the ROC curve (0.67 [0.63–0.7]) in comparison to other surrogate indices for insulin resistance. All feature selection approaches concur that the TyG-index is the most reliable surrogate insulin resistance marker for predicting CAD. Based on the Ceteris paribus profile of Random Forest the predictive ability of the TyG-index increased steadily after 9 with a positive slope, without any decline or leveling off.ConclusionDue to the simplicity of assessing the TyG-index with routine biochemical assays and given that the TyG-index was the most effective surrogate insulin resistance index for predicting CAD based on our results, it seems suitable for inclusion in future CAD prevention strategies.

Association between triglyceride glucose-body mass index and all-cause mortality in critically ill patients with acute myocardial infarction: retrospective analysis of the MIMIC-IV database.

Insulin resistance (IR) is closely related to the development of cardiovascular diseases. Triglyceride-glucose-body mass index (TyG-BMI) has been proven to be a reliable surrogate of IR, but the relationship between TyG-BMI and acute myocardial infarction (AMI) is unknown. The present study aims to determine the effects of TyG-BMI on the clinical prognosis of critically ill patients with AMI. The data of AMI patients were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were divided into four groups according to the TyG-BMI quartile. Outcomes were defined as 30-, 90-, 180-, and 365-day all-cause mortality. Kaplan-Meier (K-M) curve was used to compare survival rate between groups. Meanwhile, Cox regression analysis and restricted cubic splines (RCS) were used to explore the relationship between TyG-BMI index and outcome events. A total of 1,188 critically ill patients with AMI were included in this study. They were divided into four groups according to TyG-BMI quartiles, there were significant differences in 90-, 180-, and 365-day all-cause mortality while there was no difference in 30-day all-cause mortality. Interestingly, with the increase of TyG-BMI, the 90-, 180-, and 365-day survival rate increased first and then gradually decreased, but the survival rate after decreasing was still higher than that in the group with the lowest TyG-BMI. U-shaped relationships between TyG-BMI index and 90-, 180-, and 365-day all-cause mortality were identified using RCS curve and the inflection point was 311.1, 316.5, and 320.1, respectively, whereas the TyG-BMI index was not non-linearly associated with 30-day all-cause mortality. The results of Cox proportional hazard regression analysis are consistent with those of RCS analysis. U-shaped relationships are existed between the TyG-BMI index and 90-, 180-, and 365-day all-cause mortality in critically ill patients with AMI, but not 30-day all-cause mortality. The TyG-BMI index can be used as an effective index for early prevention of critically ill patients with AMI.

A national study exploring the association between triglyceride-glucose index and risk of hyperuricemia events in adults with hypertension

BackgroundThe triglyceride-glucose (TyG) index has been recommended as a practical surrogate of insulin resistance (IR). However, the association between the TyG index and hyperuricemia among adults with hypertension remains to be elucidated. MethodsWe included and analyzed 3134 HTN patients and 4233 non-HTN participants from the cross-sectional 2013–2018 U.S. National Health and Nutrition Examination Surveys (NHANES). Multivariable logistic regression and restricted cubic splines (RCS) were used to explore the association between the TyG index and hyperuricemia. Stratifed analyses were performed to assess the association in populations with different subgroups of hypertension. ResultsThe prevalence of hyperuricemia was higher in HTN patients (28.00 %) than in non-HTN participants (12.47 %). The multivariable logistic regression showed that the TyG index was significantly associated with hyperuricemia. After multivariable adjustment, higher TyG index levels were found to be associated with a higher prevalence of hyperuricemia in HTN patients (OR: 2.39, 95 % CI: 1.37–4.17, Ptrend < 0.001) and non-HTN participants (OR: 2.61, 95 % CI: 1.45–4.69, Ptrend < 0.001). Restricted cubic spline regression showed linearity of the associations between the TyG index and hyperuricemia (p-nonlinear > 0.05). In the subgroup analysis suggested that the positive association seemed to be strong among male, alcohol use, and diabetes group (P for interaction < 0.05). ConclusionsTyG index, a practical surrogate of IR, was linearly and positively associated with hyperuricemia in HTN and non-HTN participants. Proactive measures are needed to prevent the comorbidity of IR-driven hyperuricemia in the future.

Accessing the relationship between six surrogate insulin resistance indexes and the incidence of rapid kidney function decline and the progression to chronic kidney disease among middle-aged and older adults in China: Results from the China health and retirement longitudinal study

AimsInsulin resistance is closely related to kidney function decline, but which insulin resistance index could better predict rapid kidney function decline (RKFD) remains unclear. We aimed to evaluate the prospective association between six insulin resistance indexes: Chinese Visceral Adiposity Index (CVAI), Lipid Accumulation Product (LAP), Atherogenic Index of Plasma (AIP), triglyceride-glucose (TyG) index, triglyceride-glucose × Body Mass Index (TyGBMI) and triglyceride-glucose × waist circumference (TyGWC) with RKFD and further the progression to chronic kidney disease (CKD). Methods and measurementsData were obtained from the China Health and Retirement Longitudinal Study. Participants with normal kidney function (eGFRcr-cys ≥60 ml/min per 1.73 m2) and ≥45 years old were included at the baseline (year 2011). The eGFR was estimated by a combination of serum creatinine and cystatin C. The primary outcome was RKFD, defined as an annualized decline in eGFRcr-cys of 5 ml/min per 1.73 m2 or more. Secondary outcome was progression to CKD under the condition of RKFD, defined as an annualized decline in eGFRcr-cys of 5 ml/min per 1.73 m2 or more combined with eGFRcr-cys <60 ml/min per 1.73 m2 at the exit visit. Logistic analysis was applied for analysis of the association between six insulin resistance indexes and RKFD or progression to CKD. We use receiver operating characteristic curves to study the predictive performance of six insulin resistance indexes. Subgroup analysis were conducted by diabetes or hypertension status of the participants. ResultsA total of 3899 participants with normal kidney function were included in this study. After a 3.99 years follow-up, 191 of them ended up with RKFD. Among them, 66 participants progressed to CKD. Logistic analysis showed that per SD increase of all the six insulin resistance indexes were significantly associated with the incidence of RKFD (all P < 0.01), among which, TyGWC had the best predictive value for RKFD. There were significant association between per SD increase of CVAI, LAP, TyGBMI and TyGWC with progression to CKD (all P < 0.01), and CVAI had better predictive role than other indexes. In subgroup analysis, we found that the association between insulin resistance indexes and progression to CKD was more significant in subjects with hypertension or without diabetes. However, no significant differences were observed in the RKFD group. ConclusionsIn this study we proved six insulin resistance indexes were predictively associated with RKFD in Chinese with normal renal function over age 45. TyGWC is the best insulin resistance index for predicting RKFD. CVAI is the best index for predicting further progression to CKD.

Neglected cardiometabolic risk factors and subclinical target organ damage in post-menopausal women with normal glucose tolerance.

Menopausal transition is a crucial step in the women's cardiovascular health, and the risk stratification in apparently health post-menopausal females has been rarely assessed. Heart ultrasonography, unusually performed in such subjects, would be able to detect initial signs of organ damage. We described the cardiovascular risk profile of non-diabetic post-menopausal women, evaluating how easily computed, biochemistry-derived scores were related to ultrasonographic measures of target organ damage. We analyzed the characteristics of a cohort of two-hundred and seventy-three women consecutively referring to a prevention program of Azienda Ospedaliero-Universitaria Pisana (years 2017-2022) who underwent clinical evaluation, complete routine biochemical analyses with proxies of insulin resistance, heart and carotid ultrasonography. The cohort was further divided into four groups according to presence of isolated hypercholesterolemia (HC, 37%), isolated hypertension (HT, 5%), both HC/HT (38%), or none of them. In HC and HC/HT, LDL cholesterol was sharply above the recommended values (149 [134-171] mg/dL and 141 [123-159] mg/dL, respectively). E/e' ratio and left atrium size were augmented in HT women and further worsened in HT/HC, with an independent effect of hypertension (E/e' ß=0.055, P=0.013, left atrium volume ß=0.059, P=0.003). Presence of carotid plaques was independently linked to hypertension (ß=0.474, P=0.003). In HC and HC/HT, the Triglycerides-Glucose Index, a surrogate of insulin resistance, was higher than in the other classes (P=0.0013), and it was associated with E/A in HC and HT/HC, with a significative interaction (P=0.0004) with hypertension. Past hormone replacement therapy did not influence clinical, biochemical or echocardiographic parameters. Postmenopausal women display a high cardiovascular risk burden; a simple clinical and biochemistry screening would be advisable to identify and treat those more at risk. Cardiac ultrasonographic parameters were worse in hypertensive, hypercholesterolemic and insulin-resistant subjects, who may also deserve a deep and early instrumental characterization, especially when these conditions are associated.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case–control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients. A cohort of 90 sarcoidosis patients and a cohort of 90 control subjects were enrolled. Clinical, anamnestic, and biochemical data were collected. Results showed that TyG index values were higher in the sarcoidosis cohort than in the control group (p < 0.001), even after excluding the influence of diabetes and metabolic syndrome (p = 0.018). In the sarcoidosis cohort, TyG index was not correlated with clinical phenotyping (p = 0.358), gender (p = 0.139), radiological stage (p = 0.656), glucocorticoids cumulative dose (p = 0.682) or treatment regimen (p = 0.093), while significant positive correlations with waist circumference (p < 0.001), systolic and diastolic pressure (p = 0.041 and p = 0.029, respectively), Framingham score (p = 0.007) were found. Receiving operating characteristics curve analysis identified a TyG index optimal cut-off value of 8.64 (66.7% sensitivity, 77.8% specificity, area under the curve -AUC- 75%, 95% confidence interval -CI- 65–85, p < 0.001) to detect metabolic syndrome and a cut-off value of 8.69 (64.1% sensitivity, 70.6% specificity; AUC 67%, 95% CI 55–78, p = 0.007) to detect an intermediate cardiovascular risk according to Framingham risk score. Concluding, TyG index can be considered a useful tool for the metabolic assessment of sarcoidosis patients, given its capacity to predict metabolic syndrome and cardiovascular risk.

First-Trimester Triglyceride-Glucose Index and Triglyceride/High-Density Lipoprotein Cholesterol are Predictors of Gestational Diabetes Mellitus Among the Four Surrogate Biomarkers of Insulin Resistance.

This study seeks to assess the potential of early pregnancy Triglyceride Glucose Index (TyG), triglyceride to High-Density Lipoprotein Cholesterol ratio (TG/HDL-c), Low-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol ratio (LDL-C/HDL-C), and Total Cholesterol to High-Density Lipoprotein Cholesterol ratio (TC/HDL-C) in predicting Gestational Diabetes Mellitus (GDM). A total of 1073 adults singleton pregnant women were enrolled from June 2017 to September 2019. Complete anthropometric data and lipid profiles were measured in the first trimester (before 12 weeks gestation) and a 75g oral glucose tolerance test (OGTT) at 24-28 weeks was performed. Based on OGTT results, participants were categorised into Normal Glucose Tolerance (NGT) group (n=872) and GDM group (n=201). General data, laboratory test results, and surrogate insulin resistance indicators such as TyG index, TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were documented and compared. To compare differences between the two groups, t-test was used, Spearman correlation analysis and linear regression analysis were performed to establish associations between these indicators and insulin resistance in GDM. Receiver Operating Characteristic (ROC) curves were generated to compare the thresholds of these indicators for predicting GDM during pregnancy and to quantify overall diagnostic accuracy. Individuals with GDM had higher TyG, TG/HDL-C, and LDL-C/HDL-C levels (P < 0.001), but with no significant difference observed in TC/HDL-C. All four ratios were positively correlated with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), yet only TyG emerged as an independent risk factor for HOMA-IR. The Area under the Curve (AUC) of TyG index (0.692) was comparable to that of HOMA-IR (0.703). The cut-off points for TyG index, TG/HDL-C, and HOMA-IR in predicting GDM were 7.088, 0.831, and 1.8, respectively. HOMA-IR exhibited the highest sensitivity (79.1%), while TyG index (64.3%) and TG/HDL-C ratio (64.3%) demonstrated better specificity compared to HOMA-IR (56.3%). LDL-C/HDL-C and TC/HDL-C offered no discernible predictive advantage. Early pregnancy TyG index and TG/HDL-C can aid in identifying pregnant women at risk for GDM, potentially facilitating early and effective intervention to improve prognosis. TyG index exhibited superior predictive capability compared to TG/HDL-C.

Clinical features of early-onset type 2 diabetes and its association with triglyceride glucose-body mass index: a cross-sectional study.

The incidence of early-onset type 2 diabetes (T2D) has increased significantly, with insulin resistance (IR) and obesity being the main drivers of its onset. This study aims to investigate the clinical characteristics of early-onset T2D and its association with triglyceride glucose body mass index (TyG-BMI), an emerging surrogate of IR. A total of 1000 adults newly diagnosed with T2D were enrolled and divided into early-onset T2D (18~40 years, N=500) and late-onset T2D groups (≥40 years, N=500). Independent t and chi-squared tests were used to compare the characteristics of the two groups, and logistic regression analysis, trend tests, restricted cubic spline curves (RCSs), and receiver operating characteristic (ROC) curves were used to identify the relationship between TyG-BMI and early-onset T2D. Patients with early-onset T2D were more likely to have a higher body mass index (BMI), hemoglobin A1C (HbA1c), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), serum uric acid (SUA), triglyceride glucose index (TyG), and TyG-BMI (P < 0.05). A higher TyG-BMI was associated with an increased risk of early-onset T2D (P < 0.001). The RCSs showed a nonlinear relationship between TyG-BMI and early-onset T2D, and the slope of the curve increased with an increase in TyG-BMI (P for nonlinearity < 0.001). In the subgroup analysis, additive interactions between TyG-BMI and the risk of early-onset T2D were observed for sex, family history of diabetes, BMI, fatty liver, and hypertension (P < 0.001). ROC curve showed that the area under the curve of TyG-BMI was 0.6781, which was larger than its main components (TyG, BMI, FPG, TG). The best cutoff value was 254.865, the sensitivity was 74.6%, and the specificity was 53.6%. Patients with early-onset T2D are characterized by severe IR, metabolic disorders, and being overweight/obese and an increase in TyG-BMI is independently associated with an increased risk of early-onset T2D.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study

BackgroundStudies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population.MethodsThe data came from the National Health and Nutrition Examination Survey (NHANES 2001–2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan–Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use.Results1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found.ConclusionThe relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.