Biomarkers Of Insulin Resistance Research Articles

Isotretinoin increases non-insulin-based surrogate markers of insulin resistance in acne vulgaris patients

Background Lipid indices, particularly the triglyceride-glucose index (TyG index) and the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio, are simple, reliable, non-insulin-based surrogate markers of insulin resistance that have recently gained prominence. The aim of this study was to evaluate the effect of isotretinoin treatment on surrogate markers of insulin resistance, in particular the TyG index, in patients with acne vulgaris (AV). Materials and methods This retrospective study reviewed the records of 200 patients who received isotretinoin treatment for acne vulgaris at the Department of Dermatology and Venereology between September 2023 and March 2024. Serum fasting glucose, fasting lipid profile [triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] and other biochemical parameters were recorded. Triglyceride-glucose (TyG) index value was calculated with the formula Ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Pre-treatment values were compared with values after 5 months of treatment. Results TyG index and TG/HDL, TC/HDL, and LDL/HDL ratios all increased statistically significantly (p < 0.001). In addition, a positive correlation was found between pre- and post-treatment TyG index values and pre- and post-treatment TC/HDL, LDL/HDL and TG/HDL ratio values (p < 0.001). Among lipid measurements, triglycerides, total cholesterol, VLDL-C, LDL-C increased statistically significantly (p < 0.001), while HDL-C decreased statistically significantly (p < 0.05). Conclusion The results of this study suggest that isotretinoin treatment may increase insulin resistance in AV patients by increasing surrogate biomarkers of insulin resistance. We also suggest that the TyG index and other lipid indices can be used in treatment follow-up.

The Impact of Triglyceride-Glucose (TyG) Index on Future Cardio and Cerebrovascular Events in Patients with Acute Coronary Syndrome, During 3 Years of Follow-Up

Background: The triglyceride-glucose (TyG) index is a new alternative insulin resistance (IR) biomarker. The purpose of this study was to assess whether the TyG index can have a prognostic value in patients with acute coronary syndrome (ACS). Moreover, we wanted to compare the TyG index with HOMA index. Methods: We retrospectively enrolled 115 consecutive subjects, 81 males and 34 females, referred for ACS to our Unit of Cardiovascular Care of Policlinico Paolo Giaccone, Palermo. The subjects were divided into tertiles according to TyG index values and we performed a 3-year follow-up study. We considered as an end point new cardiovascular and cerebral events (MACCEs) during follow-up. Results: We found a significant statistical correlation between the HOMA index and the TyG index (p = 0.001). Patients with elevated TyG index have a higher incidence of MACCE at a 3-year follow-up. In our study the TyG index was an independent predictor of MACCEs (95% CI 1.8158 to 16.8068; P 0.0026) and the optimal TyG index cut-off for predicting MACCEs was 4.92 (sensitivity 76.56% and specificity 72.55%). Conclusions: The TyG index seems to significantly have an important prognostic role in patients with ACS and high values of TyG index are superior to HOMA-IR in predicting MACCEs.

Role of Peripheral and Central Insulin Resistance in Neuropsychiatric Disorders

Insulin acts on different organs, including the brain, which helps it regulate energy metabolism. Insulin signaling plays an important role in the function of different cell types. In this review, we have summarized the key roles of insulin and insulin receptors in healthy brains and in different brain disorders. Insulin signaling, as well as insulin resistance (IR), is a major contributor in the regulation of mood, behavior, and cognition. Recent evidence showed that both peripheral and central insulin resistance play a role in the pathophysiology, clinical presentation, and management of neuropsychiatric disorders like Cognitive Impairment/Dementia, Depression, and Schizophrenia. Many human studies point out Insulin Resistance/Metabolic Syndrome can increase the risk of dementia especially Alzheimer’s dementia (AD). IR has been shown to play a role in AD development but also in its progression. This review article discusses the pathophysiological pathways and mechanisms of insulin resistance in major neuropsychiatric disorders. The extent of insulin resistance can be quantified using IR biomarkers like insulin levels, HOMA-IR index, and Triglyceride glucose–body mass index (TyG–BMI) levels. IR has been shown to precede neurodegeneration. Human trials showed current treatment with certain antidiabetic drugs, as well as life style management, like weight loss and exercise for IR, have shown promise in the management of cognitive/neuropsychiatric disorders. This may pave the pathway to the development of new therapeutic approaches to these challenging disorders of dementia and psychiatric diseases. Recent clinical trials are showing some encouraging evidence for these pharmacological and nonpharmacological approaches for IR in psychiatric and cognitive disorders, even though more research is needed to apply this evidence into clinical practice. Early identification and management of IR may help as a strategy to potentially alter neuropsychiatric disorders onset as well as its progression

Vital Predictive and Prognostic Roles of Triglyceride-Glucose Index in Women With Acute Myocardial Infarction: A Retrospective Cohort Study.

As a biomarker of insulin resistance (IR) in patients with acute myocardial infarction (AMI), the triglyceride-glucose index (TyG index) has received significant attention. However, most research on AMI has focused on male patients, as it is traditionally believed to primarily affect males. Therefore, this study was conducted on a female population with AMI to investigate the potential correlation between the TyG index and their outcomes. A total of 320 women who were admitted to Fujian Provincial Hospital for AMI between January 2017 and December 2019 were included in this study. The TyG index was calculated using the following formula: ln [fasting triglycerides (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. The primary endpoint of the study was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which included all-cause mortality, myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. The association between the TyG index and unfavorable outcomes in female patients was investigated using the Cox proportional hazards regression model. It was ultimately estimated that 111 patients developed MACCEs. Females with high TyG indices had a higher prevalence of diabetes, elevated heart rates, and hemoglobin A1c, as well as a higher likelihood of undergoing thrombus aspiration and stent placement. The TyG index was found to be positively correlated with the prevalence of hypertension, diabetes, low-density lipoprotein cholesterol, hemoglobin A1c, and damaged vessels. However, this correlation was modest, yet statistically significant. Furthermore, after adjusting for conventional risk factors, the TyG index (HR: 4.292, 95% CI: 2.784-6.616, p < 0.001) was independently associated with MACCEs. As an independent risk predictor, the TyG index has the potential to enhance clinical outcomes for women with AMI.

Elevated circulating regenerating islet-derived protein 4 levels in patients with metabolic syndrome and related to its key components.

Regenerating islet-derived protein 4 (REG4) is a secretory protein that belongs to the C-type lectin superfamily. This study aims to explore the diagnostic value of REG4 as a potential biomarker for metabolic syndrome by analyzing the correlation between serum REG4 levels and metabolic syndrome. Serum REG4 levels were measured using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analysis was conducted to investigate REG4-related genes and metabolic signaling pathways. Serum REG4 levels were significantly elevated in MetS patients compared to healthy controls (439.7 vs. 422.6 ng/L, p < 0.01). In addition, circulating REG4 levels showed a positive correlation with AUGg, HbA1c, VAI, BMI, WHR, TG, TC, LDL-C, while being inversely correlated with HDL-C in the study population. Serum REG4 levels were positively correlated with MetS score. Multiple linear regression analysis identified HOMA-IR and LDL-C as independent factors affecting serum REG4 concentration. Interventional studies have shown that OGTT can significantly increase serum REG4 levels in healthy individuals, but significantly reduce REG4 levels in MetS patients. Bioinformatics analysis suggested that REG4 is linked to several metabolism-related genes and is enriched in various metabolism-related signaling pathways. REG4 may serve as a valuable biomarker and potential treatment target for insulin resistance (IR) and MetS. ChiCTR2000032878.

The associations of the triglyceride-glucose index and its combination with blood pressure on cardiovascular and all-cause mortality in hypertension: a national study.

The triglyceride-glucose (TyG) index, a reliable surrogate biomarker of insulin resistance (IR), is highlighted recently as related to cardiac disorders. However, the associations of the TyG index and its combination with blood pressure (BP) on cardiovascular and all-cause mortality in hypertension remain unclear. In this study, we included 9,635 hypertension patients from the National Health and Nutrition Examination Survey 1999-2018. During a median follow-up of 8.00 years, a total number of 853 and 2,489 in cardiovascular and all-cause deaths occurred, respectively. After full adjustments, the individual TyG index was positively associated with cardiovascular and all-cause mortality with J-shaped dose-response relationships. The lowest risk thresholds of the TyG index for cardiovascular and all-cause mortality were 9.5551 and 9.3405, respectively. In joint analyses, the highest risks of cardiovascular and all-cause mortality were observed among those with elevated levels of both BP and IR [1.64 (1.18, 2.28), P = 0.0031; 1.39 (1.14, 1.70), P = 0.0011; respectively]. In sensitivity and subgroup analyses, the results were generally robust. Our data appeal a hypothesis that future treatments for hypertension may require a combination of BP controlled and IR improvement.

Elevated Triglyceride-Glucose (TyG) Index Predicts Poor Clinical Outcomes in Critically Ill AECOPD Patients: A Retrospective Study.

The triglyceride-glucose (TyG) index is a surrogate biomarker of insulin resistance which has been widely used in intensive care unit (ICU) to predict prognosis. However, its role in critically ill acute exacerbation of COPD (AECOPD) patients remains largely unknown. A total of 645 AECOPD patients were induced in this retrospective cohort study, which extracted data from the eICU Collaborative Research Database (eICU-CRD). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). The primary endpoint includes in-hospital mortality and ICU mortality. The secondary endpoint was sepsis, acute kidney injury (AKI), and acute respiratory failure (ARF). Multivariable Cox regression analysis revealed that the TyG index was independently associated with an increased risk of in-hospital mortality (hazard ratio, HR: 1.45, 95% CI: 1.04-2.01, P = 0.028) and ICU mortality (HR: 2.13, 95% CI: 1.28-3.54, P = 0.004). Moreover, the TyG index was independently associated with an increased risk of sepsis (odds ratio, OR: 1.54, 95% CI: 1.24-1.93, P < 0.001), AKI (OR: 1.57, 95% CI: 1.26-2.02, P < 0.001) and ARF (OR: 1.50, 95% CI: 1.20-1.87, P < 0.001). Kaplan-Meier survival analysis revealed that higher TyG indexes were also related to increased in-hospital mortality and ICU mortality. In addition, the restricted cubic splines regression model demonstrated that the in-hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.897, P for non-linearity = 0.897, respectively). Elevated TyG index was independently associated with an increased risk of poor clinical outcomes in critically ill AECOPD patients. A prospective study to define TyG as a biomarker for prognosis prediction in critically ill AECOPD patients is warranted.

Identification of bio-markers for insulin resistance and sensitivity through multi-omics analysis

Aims: This study aims to identify multi-omics bio-markers for insulin resistance and sensitivity using machine learning approaches on a dataset integrated from several omics. Methods: The study included 362 patients with Insulin Resistance and Insulin Sensitivity from the Integrative Personal Omics Profiling (iPOP) database. Combining the multi-omics data from the Integrative Human Microbiome Project, this study used machine learning to reveal the relationship between insulin resistance and insulin sensitivity. Results: Of 362 patients 186 were insulin resistance and 176 were insulin sensitivity. 11,585 features were used, including clinical features, RNA transcripts, gut microbiota, cytokines, proteins, and metabolomics. We found 21 features capable of distinguishing insulin resistance from insulin sensitivity using a well-known artificial neural network (ANN) method. The model had an area under the receiver operating characteristic (AUC) of 0.97 in the validation dataset and 0.89 in the test dataset. The ANN model’s performance was compared with Random Forest model. Of the 21 new findings, two metabolites (methyl-uric acid and methylxanthine) are xenobiotics, and three RNA transcripts (SERPINF1, SLC2A2, and CHL1). Conclusion: A small number of multi-omics features identified from 11,585 potential candidates for a machine learning model can accurately predict insulin resistance and sensitivity.

Triglyceride-glucose index—A novel metabolism disorder biomarker as a promising indicator for predicting postoperative 30-day infections in elderly patients undergoing gastrointestinal-related abdominal and pelvic surgery

BackgroundThe triglyceride-glucose index, a reliable surrogate biomarker of insulin resistance, has been reported to be associated with cardiovascular events and atherosclerosis. However, few studies have investigated the association of the triglyceride-glucose index with postoperative infections. This study aimed to study the clinical risk values of the preoperative triglyceride-glucose index in postoperative infection complications in elderly patients undergoing gastrointestinal-related abdominal and pelvic surgery. MethodsThis retrospective cohort study included 3,225 older patients who underwent gastrointestinal-related abdominal and pelvic surgery between 2014 and 2019. The patients were divided into groups of triglyceride-glucose index ≤8.268 and triglyceride-glucose index >8.268 according to the optimal triglyceride-glucose index cut-off value. The outcome of interest was postoperative infections within 30 days after surgery. Primary and subgroup analyses were performed to confirm that preoperative triglyceride-glucose index qualifies as a reliable, independent risk indicator. Propensity score matching analysis was further applied to address covariates' potential residual confounding effect and test the robustness of the results. ResultsIn this study, the median age was 71 years (interquartile range, 67, 75 years), the proportion of male patients was 66.3%, and 1,058 (32.8%) were infected within 30 days after surgery. A triglyceride-glucose index >8.268 was associated with an increased risk of postoperative infections in multivariate regression analysis (odds ratio, 1.37; 95% confidence interval, 1.15–1.64; P < .001). The correlation between the triglyceride-glucose index and postoperative infections remained significantly robust (odds ratio, 1.52; 95% confidence interval, 1.21–1.92; P < .001) in the propensity score matching analysis. ConclusionsThe triglyceride-glucose index elevation determined by the optimal cutoff value of 8.268 was an independent risk factor for developing postoperative infections.

Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study

Pediatric obesity can drastically heighten the risk of cardiometabolic alterations later in life, with insulin resistance standing as the cornerstone linking adiposity to the increased cardiovascular risk. Puberty has been pointed out as a critical stage after which obesity-associated insulin resistance is more difficult to revert. Timely prediction of insulin resistance in pediatric obesity is therefore vital for mitigating the risk of its associated comorbidities. The construction of effective and robust predictive systems for a complex health outcome like insulin resistance during the early stages of life demands the adoption of longitudinal designs for more causal inferences, and the integration of factors of varying nature involved in its onset. In this work, we propose an eXplainable Artificial Intelligence-based decision support pipeline for early diagnosis of insulin resistance in a longitudinal cohort of 90 children. For that, we leverage multi-omics (genomics and epigenomics) and clinical data from the pre-pubertal stage. Different data layers combinations, pre-processing techniques (missing values, feature selection, class imbalance, etc.), algorithms, training procedures were considered following good practices for Machine Learning. SHapley Additive exPlanations were provided for specialists to understand both the decision-making mechanisms of the system and the impact of the features on each automatic decision, an essential issue in high-risk areas such as this one where system decisions may affect people’s lives. The system showed a relevant predictive ability (AUC and G-mean of 0.92). A deep exploration, both at the global and the local level, revealed promising biomarkers of insulin resistance in our population, highlighting classical markers, such as Body Mass Index z-score or leptin/adiponectin ratio, and novel ones such as methylation patterns of relevant genes, such as HDAC4, PTPRN2, MATN2, RASGRF1 and EBF1. Our findings highlight the importance of integrating multi-omics data and following eXplainable Artificial Intelligence trends when building decision support systems.

The prognostic value of triglyceride-glucose index to adverse renal outcomes in patients with type 2 diabetes mellitus: results from the cohort study of ACCORD

BackgroundThe triglyceride-glucose (TyG) index is a new and good biomarker of insulin resistance (IR). The prognostic utility of the TyG index for patients with type 2 diabetes mellitus (T2DM) remains uncertain. Our study seeks to elucidate the connection between the TyG index and adverse renal outcomes within a T2DM population, while also examining if these relationships are influenced by subgroup variations.MethodsWe analyzed data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, involving 10,196 T2DM participants, to assess the link between triglyceride-glucose levels and adverse renal outcomes. This evaluation included Restricted Cubic Spline (RCS) analysis, Kaplan–Meier survival analysis, and Multivariate Cox proportional regression. Additionally, we examined the interaction between subgroups concerning adverse renal outcomes.ResultsDuring a 7-year follow-up, 5824 patients (57.1%) experienced worsening renal function, 2309 patients (23.2%) developed albuminuria, and 280 patients (2.7%) advanced to renal failure. After adjusting for a range of confounding variables, triglyceride-glucose levels were significantly linked to both worsening renal function (p < 0.001) and the onset of albuminuria (p = 0.020). Nonetheless, no significant association was observed between triglyceride-glucose levels and renal failure (p = 0.247). Furthermore, there was no significant subgroups interaction to the associations between TyG levels and adverse renal outcomes.ConclusionOur study underscores the significant relationship between the triglyceride-glucose index and the risk of adverse renal outcomes in patients with T2DM. The TyG index, as a readily calculable measure, offers clinicians a valuable tool for anticipating the risk of adverse renal outcomes in this patient population.

The Impact of a Lifestyle Intervention on Cardiometabolic Risk Factors among Postpartum Hispanic Women with Overweight and Obesity in a Randomized Controlled Trial (Proyecto Mamá).

Maternal overweight or obesity has been associated with metabolic syndrome through 1 year postpartum, but it remains unknown whether a culturally-modified, motivationally-targeted, and individually-tailored Lifestyle Intervention could improve postpartum cardiometabolic health among Hispanic women with overweight or obesity. Proyecto Mamá was a randomized controlled trial conducted in Western Massachusetts from 2014 to 2020 in which Hispanic women with overweight/obesity were randomized to a Lifestyle Intervention (LI) involving diet and exercise or to a comparison Health and Wellness Intervention (HW). Biomarkers of cardiovascular risk (i.e., lipids, C-reactive protein) and insulin resistance (fasting insulin, glucose, HbA1c, homeostasis model assessment [HOMA-IR], leptin, adiponectin) were measured at baseline (early pregnancy), mid-pregnancy, and 6 weeks, 6 months, and 12 months postpartum. Generalized linear mixed effect models were used to evaluate differences in the change in biomarkers over the course of postpartum follow-up time. In intent-to-treat analyses among eligible women (LI; n=51, HW; n=58) there were no significant differences in changes in biomarkers of CVD risk or insulin resistance over the postpartum year; for example, the intervention effect for total cholesterol was 6.98 (SE: 6.36, p=0.27) and for HbA1c was -0.01 (SE: 0.4, p=0.85). In pooled analyses, regardless of intervention arm, women who participated in any vigorous activity had less of an increase in HbA1c (intervention effect = -0.17, SE: 0.05, p=0.002) compared to those with no vigorous activity, and similarly beneficial associations with other cardiovascular risk biomarkers (p<0.05). Women who participated in vigorous activity, regardless of their assigned intervention arm, had more favorable changes in biomarkers of insulin resistance.

Association Between the Triglyceride-Glucose Index and Serum Uric Acid to High-Density Lipoprotein (HDL) Cholesterol Ratio in Type 2 Diabetes Mellitus in Gabes City, Tunisia.

Background Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases (CVD). The triglyceride-glucoseindex (TyGi) is a novel biomarker for insulin resistance, strongly linked to CVD. Elevated serum uric acid levels and the uric acid to high-density lipoproteincholesterol ratio (UHR) are emerging as markers of metabolic syndrome and cardiovascular risk in T2DM. This study aimed to explore the association between the TyGiand UHR in T2DM patients. Objectives The aim of this study is to compare metabolic parameters in T2DM patients and assess the association between the TyGiand serum UHR. Methodology A cross-sectional case-control study was conducted at the University Hospital of Gabes, Gabes City, Tunisia with 50 T2DM patients and 50 gender-matched healthy controls. Inclusion criteria included adults aged 30-75 years with a confirmed diagnosis of T2DM on stable medication for at least three months. Exclusion criteria included other types of diabetes, significant liver or kidney disease, recent cardiovascular events, endocrine disorders, and substance abuse. Metabolic and biochemical parameters, including fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, lipid profile, and renal function, were measured. The TyGiand serum UHR were calculated and analyzed for correlations. Results T2DM patients exhibited significantly higher fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, TyGi, and serum UHR compared to controls, indicating impaired glycemic control and adverse lipid profiles. The UHR showed a positive correlation with a strong negative correlation with HDL and a positive correlation with uric acid levels. The linear regression analysis indicated a weak positive trend between the TyGi and serum UHR, although not statistically significant. Conclusion This study underscores the importance of the TyGiand serum UHRas biomarkers for evaluating metabolic and cardiovascular risk in T2DM. Further research is needed to explore their combined utility in clinical practice for early detection and management of cardiovascular complications in diabetic patients.

The combined effect of triglyceride-glucose index and high-sensitivity C-reactive protein on cardiovascular outcomes in patients with chronic coronary syndrome: A multicenter cohort study.

The triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all-cause death, nonfatal myocardial infarction, and revascularization. During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk populations and guiding management strategies among CCS patients.

Potential of Fasting C-peptide to Glucose Ratio and Triglyceride Glucose Index as Markers for β-Cell Dysfunction and Insulin Resistance in Patients With Type 2 Diabetes on Insulin Therapy.

Pathogenesis of type 2 diabetes mellitus (T2DM) is combined from initial insulin resistance (IR) and subsequent β-cell dysfunction. Insulin therapy can replace β-cell function in advanced stages. However excessive insulin therapy increases IR and may expose the patients to risk of cardiovascular disease. We aim to assess β-cell function and IR in patients with type 2 diabetes on insulin therapy by fasting C-peptide to glucose ratio (FCPGR), and triglyceride glucose (TyG) index respectively to support treatment plans. A cross-sectional study was conducted at the Galiawa Diabetes and Endocrinology Teaching Center in Erbil City, Iraq,from June 2023 to January 2024. A convenient sample of 100 patients with T2DM on insulin-based therapy were included after obtaining informed written consent and excluding conditions such as acute illness,uncertain type of diabetes, etc. Each patient was evaluated for anthropometric parameters and current treatment details. Biochemical tests were then carried out to calculate metabolic syndrome (MetS) index score, FCPGR, and TyG index. Finally, patients were divided into four subgroups according to their FCPGR and TyG index and the data were analyzed statistically. The data showed those patients with sufficient β-cell function were 60(60%), and patients withhigh TyG index were 95 (95%). There was a significant negative correlation betweenFCPGR and hemoglobin A1c (HbA1c) (p-value=0.001), while there was a positive correlation between TyG index and HbA1C (p-value=0.001). None of these markers were correlated with BMI (p-value=0.297, and 0.976), duration of T2DM (p-value=0.258, and 0.458), and dose of insulin therapy (p-value=0.901, and 0.477). Patients with sufficient β-cell function and high TyG index had the lowest HbA1C. The study provides valuable insights into the utility of FCPGR and TyG index as biomarkers for β-cell function and insulin resistance in T2DM patients on insulin therapy. The significant correlation with HbA1C underscores their potential in clinical practice. However, the lack of correlation with BMI, disease duration, and insulin dose suggests that further investigation is needed to fully understand these biomarkers' implications across diverse patient profiles.

Associations of insulin sensitivity and immune inflammatory responses with child blood lead (Pb) and PM2.5 exposure at an e-waste recycling area during the COVID-19 lockdown.

Fine particular matter (PM2.5) and lead (Pb) exposure can induce insulin resistance, elevating the likelihood of diabetes onset. Nonetheless, the underlying mechanism remains ambiguous. Consequently, we assessed the association of PM2.5 and Pb exposure with insulin resistance and inflammation biomarkers in children. A total of 235 children aged 3-7years in a kindergarten in e-waste recycling areas were enrolled before and during the Corona Virus Disease 2019 (COVID-19) lockdown. Daily PM2.5 data was collected and used to calculate the individual PM2.5 daily exposure dose (DED-PM2.5). Concentrations of whole blood Pb, fasting blood glucose, serum insulin, and high mobility group box 1 (HMGB1) in serum were measured. Compared with that before COVID-19, the COVID-19 lockdown group had lower DED-PM2.5 and blood Pb, higher serum HMGB1, and lower blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index. Decreased DED-PM2.5 and blood Pb levels were linked to decreased levels of fasting blood glucose and increased serum HMGB1 in all children. Increased serum HMGB1 levels were linked to reduced levels of blood glucose and HOMA-IR. Due to the implementation of COVID-19 prevention and control measures, e-waste dismantling activities and exposure levels of PM2.5 and Pb declined, which probably reduced the association of PM2.5 and Pb on insulin sensitivity and diabetes risk, but a high level of risk of chronic low-grade inflammation remained. Our findings add new evidence for the associations among PM2.5 and Pb exposure, systemic inflammation and insulin resistance, which could be a possible explanation for diabetes related to environmental exposure.

Effect of N-acetyl cysteine in children with metabolic dysfunction-associated steatotic liver disease-A pilot study.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD. Thirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double-blind, placebo-controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high-sensitivity c-reactive protein (hs-CRP), and interleukin-6 (IL-6) were also measured. homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and IR (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes. Sixteen-week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

The Triglyceride/HDL Ratio as a Surrogate Biomarker for Insulin Resistance.

Given the widespread occurrence of insulin resistance, a key factor in metabolic syndrome and a distinct condition altogether, there is a clear need for effective, surrogate markers. The triglyceride-to-high-density lipoprotein (TG/HDL) ratio stands out as a viable option, indicative of changes in lipid metabolism associated with insulin resistance, offering a cost-effective and straightforward alternative to traditional, more complex biomarkers. This review, in line with PRISMA guidelines, assesses the TG/HDL ratio's potential as an indirect indicator of insulin resistance. Analysing 32 studies over 20 years, involving 49,782 participants of diverse ethnic backgrounds, including adults and children, this review primarily uses a cross-sectional analysis with the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) to gauge insulin resistance. It reveals the TG/HDL ratio's varied predictive power across ethnicities and sexes, with specific thresholds providing greater accuracy for Caucasians, Asians, and Hispanics over African Americans and for men over women. Valid across different weights and ages, for adults and children, it suggests average cutoffs of 2.53 for women and 2.8 for men. The analysis supports the TG/HDL ratio as a simple, accessible marker for insulin resistance, though it advises further research on tailored cutoffs reflecting ethnic and gender differences.

Fetal femur length and risk of diabetes in adolescence: a prospective cohort study

BackgroundDiabetes is more apparent in adulthood but may be dormant in childhood and originates during early fetal development. In fetal biometry, femur length (FL) is crucial for assessing fetal growth and development. This study aimed to assess potential associations between fetal femur growth and prediabetic biomarkers in Bangladeshi children.MethodsA cohort study embedded in a population-based maternal food and micronutrient supplementation (MINIMat) trial was conducted in Matlab, Bangladesh. The children in the cohort were followed up until 15 years of age. In the original trial, pregnancy was confirmed by ultrasound before 13 gestational weeks (GWs). Afterward, ultrasound assessments were performed at 14, 19, and 30 GWs. FL was measured from one end to the other, capturing a complete femoral image. The FL was standardized by GW, and a z-score was calculated. FBG and HbA1c levels were determined in plasma and whole blood, and the triglyceride–glucose index, a biomarker of insulin resistance, was calculated as Ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable linear regression analysis using a generalized linear model was performed to estimate the effects of FL at 14, 19 and 30 GWs on prediabetic biomarkers at 9 and 15 years of age. Maternal micronutrient and food supplementation group, parity, child sex, and BMI at 9 years or 15 years were included as covariates.ResultsA total of 1.2% (6/515) of the participants had impaired fasting glucose during preadolescence, which increased to 3.5% (15/433) during adolescence. At 9 years, 6.3% (32/508) of the participants had elevated HbA1c%, which increased to 28% (120/431) at 15 years. Additionally, the TyG index increased from 9.5% (49/515) (during preadolescence) to 13% (56/433) (during adolescence). A one standard deviation decrease in FL at 14 and 19 GWs was associated with increased FBG (β = − 0.44 [− 0.88, − 0.004], P = 0.048; β = − 0.59 [− 1.12, − 0.05], P = 0.031) and HbA1c (β = − 0.01; [− 0.03, -0.005], P = 0.007; β = − 0.01 [− 0.03, − 0.003], P = 0.018) levels at 15 years. FL was not associated with diabetic biomarkers at 9 years.ConclusionMid-trimester impaired femur growth may be associated with elevated prediabetic biomarkers in Bangladeshi adolescents.

Association between estimated glucose disposal rate and subclinical coronary atherosclerosis

Background and aimsThe estimated glucose disposal rate (eGDR) is an easily accessible clinical parameter for assessing insulin resistance in patients with diabetes mellitus. In this study, we aimed to investigate the link between eGDR and subclinical coronary atherosclerosis in an asymptomatic middle-aged Korean population. Methods and resultsThis study involved 4004 subjects who underwent routine health checkups with coronary multidetector computed tomography (MDCT) at Asan Medical Center from 2007 to 2011, among whom 913 had a follow-up analysis through 2014. The eGDR was calculated using: 21.16 − (0.09 ∗ waist circumference [cm]) − (3.41 ∗ hypertension) − (0.55 ∗ glycated hemoglobin [%]). Patients were categorized into three groups according to the tertiles of eGDR. Subclinical coronary atherosclerosis was defined by significant coronary stenosis (≥50%), presence of plaques, coronary artery calcification (CAC) score, and its progression. As a result, a lower eGDR level was associated with higher prevalence of significant coronary stenosis, plaques, moderate to severe CAC, and CAC progression. Compared to other markers or risk scores, eGDR was superior to other biomarkers of insulin resistance but did not provide additional information beyond classic cardiovascular risk models like the Framingham Risk Score and Pooled Cohort Equations. ConclusionDecreased eGDR values were significantly associated with higher subclinical coronary atherosclerosis burdens in an asymptomatic middle-aged Korean population. However, its clinical implications remain uncertain due to its weaker performance compared to established cardiovascular risk models.