Markers Of Insulin Resistance Research Articles

#673 Predictive value of insulin resistance and GFR-adjusted uricemia on all-cause mortality: the URRAH study

Abstract Background and Aims Uric acid (UA) and insulin resistance (IR) are interlinked: UA contributes to adversely affects the insulin signaling pathway, while IR predicts the development of hyperuricemia. Both UA and IR are related to metabolic syndrome, which is nowadays one of the most prevalent risk factors for mortality. In the clinical scenario, the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proved to have a high correlation with IR. Lipoprotein-based markers of IR are at least as strongly associated with subclinical atherosclerosis and with newly developing atherosclerotic manifestations than Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The aim of the research was to explore the extent of interaction between IR and GFR-adjusted uricemia in determining mortality risk in a large population cohort study. Method data from 18,694 subjects were included from Uric acid Right foR heArt Healt (URRAH) database. Differences between TG/HDL-C ratio quintiles were evaluated by t-test or chi-square test. We evaluated the association between TG/HDL-C ratio and GFR-adjusted uricemia, and the development of outcomes during the follow-up study period. The primary endpoint was all-cause mortality. The Kaplan-Meier method was used to calculate the cumulative survival rate. Cox proportional hazard regression models were used to analyze the prognosis associated with IR. Results after a mean follow-up of 124 ± 64 months, there were 2,665 (14.2%) deaths for all causes. The incidence of fatal, non-fatal cardiovascular events, and all-cause mortality increased in parallel with the increase of TG/HDL-C quintiles. In both diabetic and non-diabetic patients, TG/HDL-C ratio showed a positive association with increasing of GFR-adjusted uricemia (UA/GFR ratio). TG/HDL-C ratio and GFR-adjusted uricemia significantly interact in determining all-cause mortality, even in non-diabetic patients (P < 0.0001). Subjects with higher TG/HDL-C ratio quintile had a statistically significantly higher rate of mortality than patients with lower quintiles (Fig. 1, log rank test P < 0.0001), independently by uricemia, GFR, the presence of diabetes and body mass index (BMI). Multivariate analysis showed that the TG/HDL-C ratio increase the mortality risk even after adjustment for potential confounding factors included age, diabetes, UA/GFR, BMI and statins treatment (Table 1). Conclusion For practical purposes, the easily obtainable TG/HDL-C ratio may suffice to determine the impact of insulin resistance as a risk factor. TG/HDL-C ratio interacts with GFR-adjusted uricemia in predicting mortality, even in non-diabetic patients. In conclusion, Both IR and GFR-adjusted UA levels seems to have an important predictive role on all-cause mortality, independently of age, gender, diabetes, hypertension and statins.

Association between the triglyceride-glucose index and thyroid disorders: a cross-sectional survey and Mendelian randomization analysis.

Metabolic diseases are associated with thyroid disorders. Insulin resistance is the common pathological basis of metabolic diseases. We explored the relationship between the triglyceride-glucose (TyG) index, a simple insulin-resistance marker, and thyroid disorders. Eligible TIDE (Thyroid Diseases, Iodine Status and Diabetes Epidemiology) subjects (n = 47,710) were screened with inclusion/exclusion criteria. Thyroid disorder prevalence among different TyG index groups was stratified by sex. Logistic regression evaluated the correlation between the TyG index and thyroid disorders. Multiple linear regression evaluated the association between the TyG index and TSH. Additionally, two-sample Mendelian randomization (MR) using published genome-wide association study data evaluated causality in the association between the TyG index and TSH. Men and women with greater TyG indices had a significantly greater prevalence of thyroid disorders than individuals with the lowest quartile (Q1) of TyG index (p < 0.05). Following adjustment for confounding factors, we observed that a greater TyG index significantly increased the risk of subclinical hypothyroidism in men and women (men: Q2: odds ratio (OR) [95% confidence interval (CI)] = 1.22 [1.07-1.38], p = 0.002; Q3: OR [95% CI] = 1.28 [1.12-1.45], p < 0.001; Q4: OR [95% CI] = 1.29 [1.12-1.50], p = 0.001; women: Q2: OR [95% CI] = 1.25 [1.12-1.39], p < 0.001; Q3: OR [95% CI] = 1.47 [1.31-1.64], p < 0.001; Q4: OR [95% CI] = 1.61 [1.43-1.82], p < 0.001). Only among women was the highest TyG index quartile associated with hypothyroidism (OR [95% CI] = 1.70 [1.15-2.50], p = 0.007). Additionally, in men, the association exists only in the more than adequate iodine intake population. In women, the relationship between the TyG index and thyroid disorders disappears after menopause. Furthermore, the TyG index exhibited a linear positive correlation with TSH levels. The MR analysis results revealed a causal relationship between a genetically determined greater TyG index and increased TSH (inverse-variance weighting (IVW): OR [95% CI] = 1.14 [1.02-1.28], p = 0.020); however, this causal relationship disappeared after adjusting for BMI in multivariable MR (MVMR) analysis (MVMR-IVW: OR 1.03, 95% CI 0.87-1.22, p = 0.739). A greater TyG index is associated with hypothyroidism and subclinical hypothyroidism and varies by sex and menopausal status. MR analysis demonstrated that the causal relationship between a genetically determined greater TyG index and elevated TSH levels is confounded or mediated by BMI.

Lipid-based insulin-resistance markers predict cardiovascular events in metabolic dysfunction associated steatotic liver disease

BackgroundInsulin resistance (IR) is the cornerstone of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), pathophysiologically being the key link between MASLD, metabolic disorders, and cardiovascular (CV) diseases. There are no prospective studies comparing the predictive values of different markers of insulin resistance (IR) in identifying the presence of MASLD and the associated risk of cardiovascular events (CVEs).MethodsPost hoc analysis of the prospective Plinio Study, involving dysmetabolic patients evaluated for the presence of MASLD. The IR markers considered were Homeostatic Model Assessment for IR (HOMA-IR), Triglycerides-Glycemia (TyG) index, Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C), Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI). Receiver operative characteristic (ROC) analyses were performed to find the optimal cut-offs of each IR marker for detecting MASLD and predicting CVEs in MASLD patients. Logistic and Cox multivariable regression analyses were performed, after dichotomizing the IR markers based on the optimal cut-offs, to assess the factors independently associated with MASLD and the risk of CVEs.ResultsThe study included 772 patients (age 55.6 ± 12.1 years, 39.4% women), of whom 82.8% had MASLD. VAI (Area Under the Curve [AUC] 0.731), TyG Index (AUC 0.723), and TG/HDL-C ratio (AUC: 0.721) predicted MASLD but was greater with HOMA-IR (AUC: 0.792) and LAP (AUC: 0.787). After a median follow-up of 48.7 (25.4–75.8) months, 53 MASLD patients experienced CVEs (1.8%/year). TyG index (AUC: 0.630), LAP (AUC: 0.626), TG/HDL-C (AUC: 0.614), and VAI (AUC: 0.590) demonstrated comparable, modest predictive values in assessing the CVEs risk in MASLD patients.ConclusionIn dysmetabolic patients HOMA-IR and LAP showed the best accuracy in detecting MASLD. The possible use of lipid-based IR markers in stratifying the CV risk in patients with MASLD needs further validation in larger cohorts.

Deficits in brain glucose transport among younger adults with obesity.

Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism. A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-13C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance. Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (Tmax/CMRglucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (VTCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and Tmax/CMRglucose (r = -0.477; p = 0.045). We conclude that CMRglucose is unlikely to differ between groups due to similar VTCA, and, therefore, the glucose transport Tmax is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long-term brain function and health.

Unveiling the Significance of Surrogate Markers of Insulin Resistance in Metabolic Health Assessment

Unveiling the Significance of Surrogate Markers of Insulin Resistance in Metabolic Health Assessment

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. Project Viva is a prospective prebirth cohort (n=2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n=1107), early adolescence (n=1027), and mid-adolescence (n=693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n=27) had a higher BMI z-score (β; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Relationship between the longitudinal trajectory of the triglyceride-glucose index and the development of CKD: an 8-year retrospective longitudinal cohort study.

The triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, is significantly associated with chronic kidney disease (CKD). However, there is limited research on the longitudinal trajectory of TyG index over time and its relationship with CKD. To analyse the characteristics of the longitudinal trajectory of the TyG index over time and its association with the development of CKD in a health check-up population. Participants who underwent at least three annual health check-ups at the Health Management Center of Sichuan Provincial People's Hospital from 2015 to 2022 were included in this retrospective cohort study. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The latent class mixed model (LCMM) was used to identify the TyG index trajectory of the study population. A Cox proportional hazard model was used to estimate the CKD incidence risk in different quartile groups and the association of changes in the TyG index trajectory with the development of CKD. A total of 4,921 participants were included in this study, and they were divided into four groups according to the quartiles of the baseline TyG index: Q1 (5.43-6.66), Q2 (6.67-7.04), Q3 (7.05-7.43), and Q4 (7.43-9.97). There was no difference in the risk of CKD occurrence among the TyG groups. Three different TyG index trajectories were identified in this study: a high-level group, middle-level stable group and low-level stable group, respectively. The incidence rate of CKD in the high-level TyG index trajectory group was 2.399 times greater than that in the low-level stable trajectory group (HR=2.399, 95% CI 1.167-4.935). Individuals with long-term exposure to high TyG index levels had a significantly greater risk of CKD. Routine monitoring of the TyG index and its longitudinal trend will aid in the risk stratification of CKD in the general population and will be helpful for CKD prevention and targeted management.

Triglyceride-Glucose Index: A Candidate Prognostic Marker in HR-Positive/HER2-Negative Metastatic Breast Cancer Patients Treated With CDK4/6 Inhibitors

Aims and ObjectivesAlthough cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) are a vital part of the treatment of hormone receptor (HR)-positive/HER-2-negative metastatic breast cancer (BC), individuals have different sensitivities to CDK4/6i, indicating the need for biomarkers. The fasting triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance (IR). Herein, we investigated the prognostic significance of the fasting triglyceride glucose (TyG) index in HR+/HER2- metastatic BC patients treated with CDK4/6i plus endocrine therapy (ET). MethodsAbout 333 patients with HR+/HER2-metastatic BC treated with CDK4/6i plus ET were analyzed retrospectively. The TyG index was calculated within 3 months before the initiation of CDK4/6i plus ET. The median value of 8.43 was taken as the cutoff for the TyG index. ResultsThe median overall survival (OS) was 73.6 months (95% CI, 66.0-81.1) in the whole cohort. The progression-free survival (PFS) was significantly longer in the low-TyG subgroup than in the high-TyG subgroup (30.1 vs. 21.3 months, multivariate adjusted [HR] = 0.666, 95% CI, 0.450-0.987, P = .043). While the median OS was not reached in the low TyG subgroup, it was 69.0 months in the high TyG subgroup (multivariate-adjusted HR = 0.513, 95% CI, 0.281-0.936, P = .030). Although the ORR and DCR were numerically greater in the low-TyG subgroup, no significant differences were observed between the low-TyG subgroup and high-TyG subgroup (28.1% vs. 24.7%, P = .476; 83.2% vs. 80.1%, P = .463, respectively). ConclusionsThese data imply that the TyG index could be a predictive biomarker for the therapeutic efficacy of CDK4/6is. Extensive prospective studies are needed to confirm these findings.

Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: a national cohort study

BackgroundBoth the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and systemic inflammation are predictors of cardiovascular diseases; however, little is known about the coexposures and relative contributions of TyG index and inflammation to cardiovascular diseases. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted longitudinal analyses to evaluate the joint and mutual associations of the TyG index and high-sensitivity C-reactive protein (hsCRP) with cardiovascular events in middle-aged and older Chinese population.MethodsThis study comprised 8 658 participants aged at least 45 years from the CHARLS 2011 who are free of cardiovascular diseases at baseline. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Cardiovascular events were defined as the presence of physician-diagnosed heart disease and/or stroke followed until 2018.We performed adjusted Cox proportional hazards regression and mediation analyses.ResultsThe mean age of the participants was 58.6 ± 9.0 years, and 3988 (46.1%) were females. During a maximum follow-up of 7.0 years, 2606 (30.1%) people developed cardiovascular diseases, including 2012 (23.2%) cases of heart diseases and 848 (9.8%) cases of stroke. Compared with people with a lower TyG index (< 8.6 [median level]) and hsCRP < 1 mg/L, those concurrently with a higher TyG and hsCRP had the highest risk of overall cardiovascular disease (adjusted hazard ratio [aHR], 1.300; 95% CI 1.155–1.462), coronary heart disease (aHR, 1.294; 95% CI 1.130–1.481) and stroke (aHR, 1.333; 95% CI 1.093–1.628), which were predominant among those aged 70 years or below. High hsCRP significantly mediated 13.4% of the association between the TyG index and cardiovascular disease, while TyG simultaneously mediated 7.9% of the association between hsCRP and cardiovascular risk.ConclusionsThe findings highlight the coexposure effects and mutual mediation between the TyG index and hsCRP on cardiovascular diseases. Joint assessments of the TyG index and hsCRP should be underlined for the residual risk stratification and primary prevention of cardiovascular diseases, especially for middle-aged adults.

Orexin A is a new marker of insulin resistance in polycystic ovary syndrome

Orexin A is a new marker of insulin resistance in polycystic ovary syndrome

Increased calcium intake from skimmed milk in energy-restricted diets reduces glycation markers in adults with type 2 diabetes and overweight: A secondary analysis of a randomized clinical trial

The effect of calcium (Ca) on glycation markers is unknown. We hypothesized that increased Ca intake from skimmed milk associated with an energy-restricted diet intake will reduce glycation markers. This reduction will be associated with a greater improvement in markers of metabolic control in adults with type 2 diabetes, overweight, and low habitual Ca intake (<600 mg/d). In this secondary data analysis based on a crossover clinical trial, 14 adults were allocated into 2 groups: high calcium (shake containing 700 mg Ca/day) or low calcium (shake with 6.4 mg Ca/day), for 12 consecutive weeks per session. Energy-restricted diets were also prescribed (-500 kcal/d, 800 mg of dietary Ca/d) to all participants. Advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), glycemic control, and lipid profile were assessed at baseline and after 12 weeks. High-calcium serum AGE concentrations and AGE/sRAGE ratio were lower at the end of the study. ΔAGE and ΔAGE/sRAGE ratio were both positively associated with Δtriglycerides, Δtotal cholesterol, Δtriglyceride-glucose index and variations, and Δvisceral adiposity index. ΔAGE/sRAGE was positively associated with Δfructosamine and Δhigh-density lipoprotein-cholesterol, and negatively associated with male sex. Consumption of approximately 1200 mg/day of calcium (3 servings of skim milk) reduced serum AGEs concentrations and the AGE/sRAGE ratio in individuals with diabetes. In general, positive changes in glycation markers are associated with lipid profile, insulin resistance, and adiposity markers worsening. ΔAGEs/ΔsRAGE ratio seems to be a better marker of metabolic status than ΔAGEs and ΔsRAGE alone. Registered in ClinicalTrials.gov (NCT02377076).

TYG INDEX AS PREDICTOR OF METABOLIC SYNDROME IN YOUNG TO-MIDDLE AGE STAGE I HYPERTENSIVES, UNTREATED AT THE BASELINE

Objective: Tyg index, a surrogate marker of insulin resistance, was shown to be a predictor of development of metabolic syndrome (MS) among diabetes patients and general population while the predictive value among young hypertensives is less known. The aim of the present study was to investigate the predictive capacity of tyg index for incident MS among young untreated hypertensives. Design and method: we investigated 949 young-to-middle age stage I hypertensives from the HARVEST study, mean age 32.4±8.7 years, mean BMI 24.7±3.2 kg/m2, 69.2% males, without MS at baseline. Mean 24h blood pressure (BP) at entry 130.0±10.9/81.0±8.3 mmHg. Tyg index was calculated according to the usual formula. Patients were divided into tyg quintiles:7.008-7.895, 7.896-8.199, 8.200-8.423, 8.424-8.585, &gt;=8.586 respectively. The risk of MS was calculated by means of survival Cox analyses adjusted for several confounders. Results: Patients in the highest quintiles were significantly older 35.3±8.1 years and heavier 25.3±3.3 kg/m2 than the bottom ones (p&lt;0.001). Also baseline metabolic parameters were worse in top quintile (serum glucose 96.2±14.1, uric acid 5.3±1.2 mg/dl, total cholesterol 212.1±35.3 mg/dl, HDL 51.8±10.2 mg/dl) in comparison to the lower ones (p&lt;0.001 for all comparisons). Baseline 24h BP values did not differ according to Tyg quintile, while heart rate was higher in the top quintile (74.3±8.4 bpm, p&lt;0.001). During 8.1 years of follow-up, 76.3% of subjects developed new onset MS. Again, metabolic parameters were worst in the highest tyg quintile (serum glucose 97.9±15.4 mg/dl, total cholesterol 225.9±44.7 mg/dl, and HDL 52.1±15.2 mg/dl, as was final BMI (26.2±3.6Kg/m2, p&lt;0.001 for all comparisons). Final 24h BP did not differ according to Tyg quintile while heart rate was higher in the highest quintile (p&lt;0.001). In multivariate Cox analysis patients in the 4th and 5th quintiles presented the highest risk of new onset MS (HR 1.51 (1.11-2.06) p=0.009; HR 1.46 (1.09-1.46)p=0.011, respectively), in comparison to the bottom quintile. Conclusions: The risk of development of metabolic syndrome was significantly increased among patients in the top tyg quintiles, confirming its predictive capacity as a surrogate marker of insulin resistance among young stage I hypertensives.

Enzymatic detection of α-hydroxybutyrate, an important marker of insulin resistance, and comparison with LC-MS/MS detection

AimThe metabolite α-hydroxybutyrate (α-HB) is an important marker of insulin resistance and impaired glucose tolerance allowing to identify patients at risk of developing diabetes and related metabolic disorders before any symptoms become apparent. At present, its exact quantification requires mass spectrometry (LC-MS), which is not compatible with routine laboratory use. Accordingly, a simple enzymatic-based method was assessed and its applicability and measuring accuracy compared with LC-MS was investigated. MethodsStandards, serum, and plasma samples containing α-HB were prepared with routine procedures and their α-HB contents measured with the XpressGT® enzymatic test kit photometrically or with LC-MS and multiple reaction monitoring. Resultsα-HB detection with XpressGT® yielded highly linear calibration curves and 102 % recovery of stocks added to commercial samples. Stability of the analyte in serum and plasma samples prepared with various anti-coagulants was >90 % after 46 h for several widely used preparations and recovery after 3 freeze-thaw cycles was ≥95 % with these anti-coagulants. A direct comparison of 75 samples indicated very good agreement of α-HB levels determined by both methods, 86 % of XpressGT® samples being within ±20 % of LC-MS values and even 93 % within ±20 % considering only samples above 30 μM concentration. ConclusionXpressGT®-based detection of α-HB is an easily applicable method which can be used for accurate and reliable quantification of the metabolite in clinical practice. Routine α-HB determination in patients at risk of developing diabetes would allow early establishment of preventive measures or pharmacological intervention reducing the risk for the onset of serious diabetes-related health problems.

Triglyceride-glucose (TYG) index as a screening marker of insulin resistance in Indian population

Triglyceride-glucose (TYG) index as a screening marker of insulin resistance in Indian population

THE ROLE OF TYG INDEX AS PREDICTOR OF CARDIOVASCULAR EVENTS AMONG YOUNG TO-MIDDLE-AGE STAGE I HYPERTENSIVES

Objective: The triglyceride-glucose index (TYG), a surrogate marker of insulin resistance, was shown to be associated with an increased risk of cardiovascular events among people with diabetes or the metabolic syndrome, while its prognostic capacity among young hypertensives is less explored. The aim of the present study was to investigate the role of TYG as predictor of cardiovascular outcomes among young stage I hypertensives, untreated at baseline. Design and method: We investigated 1210 subjects from the HARVEST study, mean age 33.1±8.5 years, 72.8% males. TYG was calculated according to the usual formula. BP was measured with 24-hour ambulatory monitoring. For the analyses, patients were divided into TYG quartiles: 7.008-8.061, 8.063-8.423, 8.424-8.690, 8.691-10.678, respectively. The risk of major adverse cardiovascular events (MACE) was explored by means of survival Cox analyses adjusting for several confounders and risk factors, including lifestyle factors, 24-hour BP and cholesterol. Results: TYG was correlated with BMI (r=0.348, p&lt;0.001), age (0.237, p&lt;0.001), serum uric acid (r=0.349, p&lt;0.001), total cholesterol (r=0.422, p&lt;0.001) and HDL-cholesterol (-0.393, p&lt;0.001), and diastolic BP (0.132, p&lt;0.001). Subjects in the top TYG quartile had the highest percentage of smokers (p&lt;0.001), coffee users (p=0.038) and alcohol drinkers (p=0.010). TYG was significantly correlated with left ventricle mass index (r=0.08, p=0.021), left ventricular septum thickness (r=0.15, p&lt;0.001), and posterior wall thickness (r=0.17, p&lt;0.001). During 17.4 years of follow-up, 108 MACE were accrued. In multivariate Cox analysis the risk of MACE was higher in the two highest TYG quartiles than in the bottom quartile. For the top quartile the hazard ratio was 2.46 (95%CI, 1.17-5.20, p=0.018). The association remained significant also when the lifestyle factors were included in the regression with a hazard ratio of 2.43 (95%CI, 1.14-5.17, p=0.022). This was driven mainly by the strong association found in men with a hazard ratio of 4.84 (95%CI, 1.63-14.39, p=0.004). Conclusions: TYG index is a surrogate marker of insulin resistance, easy to calculate, which significantly correlates with several other metabolic parameters and with left ventricular wall thickness and mass. It is a predictor of adverse cardiovascular outcomes especially in male individuals.

Triglyceride-Glucose Index, HOMA Index and metabolic syndrome in a sample of adult men.

Metabolic syndrome (MetS) and its components are directly associated with cardiovascular risk. Insulin resistance (IR) is the most common pathophysiological feature of MetS. A novel index, the triglyceride-glucose index (TyG), is considered a surrogate marker of IR. Hence, we estimated the ability of TyG to predict the risk to develop MetS over a follow-up period of 8 years. In addition, we compared the predictive role of TyG and that of the HOmeostatis Model Assessment (HOMA) of IR index (a widely used tool to evaluate IR). The analysis included 440 adult men (The Olivetti Heart Study) without MetS at baseline. The optimal cut-off point of the association of continuous TyG or HOMA-IR with MetS was identified by ROC analysis. During the follow-up period, 21.6% of participants developed MetS. Baseline TyG and HOMA-IR were both significantly greater in those who developed MetS than in those who did not. These results were confirmed upon adjustment for the main confounders. After stratification by the optimal cut-off point, TyG >4.78 was a significant predictor of MetS, also after adjustment for main confounders. Likewise, HOMA-IR >2.14 was associated with the risk of MetS development in multivariate models. The results of this prospective study indicate a significant predictive role of TyG on the risk of MetS, independently of the main confounders. They suggest that TyG may serve as a low-cost and simple non-invasive marker for cardio-metabolic risk stratification, with respect to more complex and expensive assays of IR requiring the insulin measurement.

Association Between Adequate Serum 25(OH)D Levels and Atherogenic Dyslipidemia in Young Adults.

This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults. A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways. The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein. This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

The prognostic impact of insulin resistance surrogates in patients with acute myocardial infarction with and without type 2 diabetes.

Cardiovascular disease is the major cause of morbidity and mortality, particularly in type 2 diabetes mellitus (T2DM). Novel markers of insulin resistance and progression of atherosclerosis include the triglycerides and glucose index (TyG index), the triglycerides and body mass index (Tyg-BMI) and the metabolic score for insulin resistance (METS-IR). Establishing independent risk factors for in-hospital death and major adverse cardiac and cerebrovascular events (MACCE) in patients with myocardial infarction (MI) remains critical. The aim of the study was to assess the risk of in-hospital death and MACCE within 12months after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with and without T2DM based on TyG index, Tyg-BMI and METS-IR. Retrospective analysis included 1706 patients with STEMI and NSTEMI hospitalized between 2013 and 2021. We analyzed prognostic value of TyG index, Tyg-BMI and METS-IR for in-hospital death and MACCE as its components (death from any cause, MI, stroke, revascularization) within 12months after STEMI or NSTEMI in patients with and without T2DM. Of 1706 patients, 58 in-hospital deaths were reported (29 patients [4.3%] in the group with T2DM and 29 patients [2.8%] in the group without T2DM; p = 0.1). MACCE occurred in 18.9% of the total study population (25.8% in the group with T2DM and 14.4% in the group without T2DM; p < 0.001). TyG index, Tyg-BMI and METS-IR were significantly higher in the group of patients with T2DM compared to those without T2DM (p < 0.001). Long-term MACCE were more prevalent in patients with T2DM (p < 0.001). The area under the ROC curve (AUC-ROC) for the prediction of in-hospital death and the TyG index was 0.69 (p < 0.001). The ROC curve for predicting in-hospital death based on METS-IR was 0.682 (p < 0.001). The AUC-ROC values for MACCE prediction based on the TyG index and METS-IR were 0.582 (p < 0.001) and 0.57 (p < 0.001), respectively. TyG index was an independent risk factor for in-hospital death in patients with STEMI or NSTEMI. TyG index, TyG-BMI and METS-IR were not independent risk factors for MACCE at 12month follow-up. TyG index and METS-IR have low predictive value in predicting MACCE within 12months after STEMI and NSTEMI.

Prognostic Value of Hyperglycemia and Insulin Resistance Among Patients with Confirmed COVID-19 Infections at Admission to the Alexandria Fever Hospital, Egypt.

Background: The interaction between COVID-19 infection, hyperglycemia, and insulin resistance (IR) may lead to poor outcome. Methods: This prospective study included 100 adult participants without diabetes attending Alexandria Fever Hospital with confirmed COVID-19 infections. They were classified into four groups according to disease severity using World Health Organization (WHO) criteria. Demographic and clinical parameters were collected. Laboratory investigations were obtained. Another follow-up fasting plasma glucose (FPG) value was measured after 3 months in cured patients. Results: Admission FPG, follow-up FPG, lipid profile, markers of IR, and inflammation were significantly higher in severe and critical cases than in mild and moderate cases with increasing values with increased severity. Furthermore, these parameters were significantly higher in died cases compared with cured cases. Admission FPG, TyG index, and homeostatic model assessment (HOMA)-IR showed significant positive correlations with follow-up FPG. Admission FPG was the only independent mortality predictor in multivariate analysis (P = 0.027) with 1.7-folds increased mortality risk with each 10 mg/dL increments. Values exceeding 117 mg/dL, 2.2, and 6.33 for admission FPG, HOMA-IR, and Fasting Insulin Resistance Index, respectively, were able to predict mortality in the studied sample. Conclusions: These results will help in identifying patients at high risk of severe infection and death at admission and take early actions to improve outcome.

Association Between Triglyceride-Glucose Index and Diabetic Retinopathy: A Meta-Analysis.

The objective of this study was to assess the relationship between the triglyceride-glucose (TyG) index, a recently proposed marker of insulin resistance, and the occurrence of diabetic retinopathy (DR), a complication associated with cardiovascular risk. This systematic review and meta-analysis aimed to evaluate the association between the TyG index and DR. To achieve the objective of the meta-analysis, an extensive search was conducted on databases such as PubMed, Embase, and Web of Science to identify observational studies with longitudinal follow-up. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. Twelve observational studies from 11 reports were included in the meta-analysis, which involved 16 259 patients with type 2 diabetes (T2D). Among them, 4302 (26.5%) were diagnosed as DR. Pooled results showed that a higher TyG index was associated with a higher risk of DR [odds ratio (OR) for the fourth versus the first quartile of TyG index: 1.91, 95% confidence interval (CI): 1.44 to 2.53, p<0.001; I2=72%]. Meta-analysis of TyG index analyzed in continuous variable showed consistent results (OR for per 1 unit increment of TyG index: 1.41, 95% CI: 1.08 to 1.86, p=0.01; I2=82%). Subgroup analysis showed that adjustment of HbA1c or the duration of diabetes did not significantly affect the results (p for subgroup difference all>0.05). In conclusion, a high TyG index was associated with the risk of DR in T2D patients.