Inhibition of ATGL alleviates MASH via impaired PPARα signalling that favours hydrophilic bile acid composition in mice.

BACKGROUND AND AIMS: Adipose triglyceride lipase (ATGL) is an attractive therapeutic target in insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigated the effects of pharmacological ATGL inhibition on the development of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis in mice. METHODS: Streptozotocin-injected male mice were fed an HFD to induce MASH. Mice receiving the ATGL inhibitor, Atglistatin (ATGLi), were compared to controls using liver histology, lipidomics, metabolomics, 16s rRNA, and RNA sequencing. Human ileal organoids, HepG2 cells, and Caco2 cells treated with the human ATGL inhibitor NG-497, HepG2 ATGL knockdown cells, gel-shift, and luciferase assays were analysed for mechanistic insights. We validated its benefits on steatohepatitis and fibrosis in a low-methionine choline-deficient mouse model. RESULTS: ATGLi improved serum liver enzymes, hepatic lipid content, and histological liver injury. Mechanistically, ATGLi attenuated PPARα signalling, favouring hydrophilic bile acid (BA) synthesis with increased Cyp7a1, Cyp27a1, Cyp2c70, and reduced Cyp8b1 expression. Additionally, reduced intestinal Cd36 and Abca1, along with increased Abcg5 expression, were consistent with reduced levels of hepatic TAG-species containing PUFAs like linoleic acids as well as reduced cholesterol levels in the liver and plasma. Similar changes in gene expression associated with PPARα signaling and intestinal lipid transport were observed in ileal organoids treated with NG-497. Furthermore, HepG2 ATGL knockdown cells revealed reduced expression of PPARα target genes and upregulation of genes involved in hydrophilic BA synthesis, consistent with reduced PPARα binding and luciferase activity in the presence of the ATGL inhibitors. CONCLUSIONS: Inhibition of ATGL attenuates PPARα signalling, translating into hydrophilic BAs, interfering with dietary lipid absorption, and improving metabolic disturbances. The validation with NG-497 opens a new therapeutic perspective for MASLD. IMPACT AND IMPLICATIONS: The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is a crucial public health concern. Since adherence to behavioural interventions is limited, pharmacological strategies are necessary, as highlighted by the recent FDA approval of resmetirom. However, since our current mechanistic understanding and pathophysiology-oriented therapeutic options for MASLD are still limited, novel mechanistic insights are urgently needed. Our present work uncovers that pharmacological inhibition of ATGL, the key enzyme in lipid hydrolysis using Atglistatin (ATGLi), improves metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and associated key features of metabolic dysfunction in a mouse model of MASH and MCD-induced liver fibrosis. Mechanistically, we demonstrated that attenuation of PPARα signalling in the liver and gut favours hydrophilic bile acid composition, ultimately interfering with dietary lipid absorption. One of the drawbacks of ATGLi is its lack of efficacy against human ATGL, thus limiting its clinical applicability. Against this backdrop, we could show that ATGL inhibition using the human inhibitor NG-497 in human primary ileum-derived organoids, Caco2 cells, and HepG2 cells translated into therapeutic mechanisms similar to ATGLi. Collectively, these findings open a new avenue for MASLD treatment development by inhibiting human ATGL activity.

Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.

AIMS: Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients. METHODS: We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5 mg colchicine twice daily for 3 months. The soluble suppressor of tumorigenicity (sST2), interleukin-1ß, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3 months. RESULTS: No significant effects were reported for colchicine on sST2, interleukin-1ß levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P = .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P = .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R = .459, P < .001) at the end of follow-up. CONCLUSION: Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI. GOV REGISTRATION ID: NCT06054100.

The influence and mechanism of fish collagen peptide and egg yolk lecithin on proliferation and lipid composition in feline adipocytes.

The influences of fish collagen peptide (FCP) and egg yolk lecithin (EYL) on the proliferation, fat accumulation and triglyceride content in feline adipocytes were investigated in this work, aiming at unveiling the mechanism of fat accumulation for cheek of feline animals. The lipogenic changes of adipocytes in the presence of FCP and EYL were determined by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results demonstrated that FCP of 10 mg/mL had the strongest cell activity, with a relative increment rate of 156 ± 0.23%, and the triglyceride content reached 215.9 ± 3.86 mmol/L. By comparison, it was observed that an EYL concentration of 5 mg/mL elicited the highest cell activity, exhibiting a relative increment rate of 152 ± 0.60%, and the level of triglyceride content was noted to reached 256.56 ± 25.68 mmol/L. After the feline adipocytes were treated with different concentrations of two active substances, fat formation and lipid droplets were found by oil red O staining. Liposome analyses confirmed that the formation of lipid compounds was regulated by FCP and EYL through pathways involved in lipid metabolism, notably including inositol phosphate insulin resistance, and phosphatidylinositol signaling pathways. This regulation was found to enhance cell vitality and facilitate fat accumulation. These findings provide a new strategy for the development of nutritional and healthy products or foods that promote feline cheek.

The triglyceride-glucose index dynamic trajectory reveals the association between the clinical subphenotype of insulin resistance and mortality in patients with sepsis.

BACKGROUND: The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. METHODS: In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. RESULTS: A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00-1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. CONCLUSION: Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients.

Gestational diabetes complicated with preterm birth: a retrospective cohort study.

OBJECTIVE: To delineate the clinical characteristics of preterm birth (PTB) in the context of gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted, including 14,314 pregnant women with GDM who delivered at Fujian Provincial Maternity and Children's Hospital from January 1, 2018, to December 31, 2021. PTB was stratified into late PTB (34-36 weeks of gestation) and early PTB (< 34 weeks) and pregnancy complications were analyzed. RESULTS: Compared to the term birth (TB) cohort, a higher prevalence of premature rupture of membranes, hypertensive diseases of pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), anemia and cervical insufficiency was observed in the PTB cohort. Notably, early PTB increased the incidence of HDP, ICP, anemia and cervical insufficiency compared to late PTB. In the early stages of pregnancy, early PTB was characterized by elevated triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C) levels compared to late PTB. In the late pregnancy stages, early PTB was associated with increased white blood cell (WBC) and neutrophil counts. No disparities were observed in 75 g oral glucose tolerance test (OGTT) between early and late PTB. CONCLUSION: Enhanced surveillance and management of GDM, particularly in the presence of HDP, ICP and anemia, are imperative to mitigate the risk of PTB. The lipid profile may serve as a predictive tool for early PTB in the early stages of pregnancy, warranting further studies.

Association between triglyceride glycemic index and ejection fraction preserved heart failure in hypertensive patients.

Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular disease consequences and a reliable surrogate measure of insulin resistance (IR). However, the correlation analysis between triglyceride glucose index and heart failure with preserved ejection fraction in patients with essential hypertension remains unknown. Methods: A single-center, retrospective study was conducted with patients diagnosed with essential hypertension at the First Affiliated Hospital of Xinjiang Medical University, from December 2018 to September 2020. Participants were selected based on specific inclusion and exclusion criteria, with their clinical data and laboratory tests collected. The study employed Spearman's correlation analysis, logistic regression models, restricted cubic spline plots, and receiver operating characteristic (ROC) curves to investigate the relationships between the TyG index and HFpEF. Results: Out of 1,602 enrolled hypertensive patients, 992 were included in the analysis after applying exclusion criteria. Patients were categorized into tertiles based on the TyG index, which showed that patients in the highest tertile had characteristics associated with a higher risk of HFpEF, including age, body mass index (BMI), systolic blood pressure (SBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and left ventricular mass index (LVMI). A significant, independent association between the TyG index and HFpEF was confirmed, with an odds ratio (OR) of 5.127 (95% CI [3.894-6.856]). Furthermore, an S-shaped nonlinear relationship was observed between the TyG index and the incidence of HFpEF (nonlinear p < 0.001). TyG index (AUC: 0.824, 95% CI [0.795-0.854]), NT-proBNP (AUC: 0.840, 95% CI [0.816-0.864]), and LVMI (AUC: 0.847, 95% CI [0.820-0.875]) showed good predictive ability for HFpEF. In addition, the TyG+LVMI combination demonstrated the strongest predictive ability (AUC: 0.907, 95% CI [0.887-0.927]). Conclusion: The study underscores a significant association between IR, as indicated by the TyG index, and the development of HFpEF in hypertensive patients. It highlights the critical role of metabolic dysfunction in the pathophysiology of HFpEF, advocating for a broader perspective on cardiovascular risk management.

Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes.

PURPOSE OF REVIEW: Individuals with diabetes face increased risk of atherosclerotic cardiovascular disease (ASCVD), in part due to hyperlipidemia. Even after LDL cholesterol-lowering, residual ASCVD risk persists, part of which may be attributed to elevated remnant cholesterol. We describe the impact of elevated remnant cholesterol on ASCVD risk in diabetes. RECENT FINDINGS: Preclinical, observational, and Mendelian randomization studies robustly suggest that elevated remnant cholesterol causally increases risk of ASCVD, suggesting remnant cholesterol could be a treatment target. However, the results of recent clinical trials of omega-3 fatty acids and fibrates, which lower levels of remnant cholesterol in individuals with diabetes, are conflicting in terms of ASCVD prevention. This is likely partly due to neutral effects of these drugs on the total level of apolipoprotein B(apoB)-containing lipoproteins. Elevated remnant cholesterol remains a likely cause of ASCVD in diabetes. Remnant cholesterol-lowering therapies should also lower apoB levels to reduce risk of ASCVD.

High-density lipoprotein functionality in cholesterol efflux in early childhood is related to the content ratio of triglyceride to cholesterol.

Cholesterol efflux capacity (CEC), commonly measured as a useful risk marker of atherosclerotic cardiovascular disease, depends on high-density lipoprotein (HDL) functionality and its concentration. We defined the relative HDL functionality in cholesterol efflux, not influenced by HDL concentration, as the ratio of measured CEC to standardized CEC (stCEC) based on HDL-cholesterol (HDL-C) of each individual using the curve regression equation obtained from the correlation. HDL-C, CEC, and CEC/stCEC levels in the < 28-day-old participants (neonates) were significantly low compared to those of the ≥ 28-day-old participants, indicating that the low CEC levels in the neonates depend on not only lower HDL-C but also lower HDL functionality. The low level of CEC/stCEC was remarkable in neonates born at < 34 weeks of gestation and did not improved to the reference level (1.000) until the infantile period. The relatively low or high CEC/stCEC ratios in neonates and infants were associated with lower or higher HDL-TG and HDL-TG/HDL-C ratio, respectively. However, no apparent effect of HDL-TG and HDL-TG/HDL-C ratio on CEC/stCEC was observed in the ≥ 1-year-old participants, indicating that HDL functionality in cholesterol efflux could be associated with the various HDL particles with various lipid compositions, but not just with HDL-TG and HDL-TG/HDL-C ratio.

Elevated triglyceride-glucose index predicts poor outcome in patients with intracranial atherosclerotic stenosis after extracranial and intracranial bypass.

BACKGROUND AND PURPOSE: The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting. METHODS: 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan-Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index. RESULTS: A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p < 0.001) and (1.27, 95%CI 1.16-1.40, p < 0.001) respectively. The area under the curve (AUC) in the model with the TyG index for predicting the occurrence of MACCEs and anastomotic stenosis were 0.708 (95%CI 0.665-0.748) and 0.731 (95%CI 0.689-0.770) respectively. The addition of the TyG index significantly improved the global performance of the baseline model according to the C-statistics, NRI, and IDI (All p < 0.05). CONCLUSIONS: Higher TyG levels were associated with poorer outcomes in ICAS patients after EC-IC bypass. TyG could be a key factor in managing ICAS risk and standardizing the indications for EC-IC bypass.

Evaluating the impact of chronic kidney disease and the triglyceride-glucose index on cardiovascular disease: mediation analysis in the NHANES.

BACKGROUND: This study explores the intricate relationship between Chronic Kidney Disease (CKD), the Triglyceride-Glucose (TyG) index, and Cardiovascular Disease (CVD) in a U.S. adult population. It focuses on understanding how the TyG index, as a marker of insulin resistance, relates to cardiovascular risk in the presence of CKD. METHODS: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. The study involved classifying stages of CKD, calculating the TyG index, and applying statistical analyses including logistic regression. RESULTS: The investigation revealed that individuals with CKD, who comprised 49% males with an average age of 47 years, exhibited a higher incidence of CVD. The study demonstrated that before adjusting for the TyG index, the odds ratio (OR) for the association between CKD and CVD was 1.77. Importantly, the TyG index was found to mediate 10% of the association between CKD and CVD. Moreover, a significant synergistic interaction was observed between a high TyG index and CKD, with the combined presence of these conditions increasing the risk ratio for CVD to 3.01. CONCLUSION: The findings highlight the crucial role of insulin resistance in the link between CKD and CVD. The paper discusses the implications of chronic inflammation and endothelial dysfunction in CKD patients and the importance of the TyG index in assessing cardiovascular risk.

Investigation of the risk factors associated with prediabetes in normal-weight Qatari adults: a cross-sectional study.

Type 2 diabetes is one of the most prevalent chronic diseases in the world, and more people than ever before have impaired glucose tolereance, or prediabetes. Many patients with impaired glucose tolerance and undiagnosed diabetes do not know that their glucose metabolism system has been in a state of disorder. Every year, about 5-10% of prediabetics develop diabetes. One of the important achieving factors may be the increase in blood lipids. However, it is not clear whether triglyceride is associated with impaired glucose tolerance and prediabetes in the Qatari population. Therefore, we investigated the relationship between the first several clinical variables and prediabetes status in normal and overweight populations. We conducted a cross-sectional study using data from the Qatar Biobank program. The study included 5,996 participants who were adults over the age of 20. We collected information about participants' fasting blood glucose levels with other clinical measurements and used various machine learning models and logistic regression to study the association between the clinical measurements and prediabetes for normal and overobese weight groups. The use of several machine learning models showed that, after adjusting the potential confounding factors such as age and sex, Triglyceride has been demonstrated to be positively correlated with prediabetes, and there was a special population dependence phenomenon. Among them, nonobese people (p < 0.05). The effect value and 95% confidence interval and OR of triglyceride on prediabetes was 2.79 and (e0.78, e1.28), respectively.

The triglyceride glucose related index is an indicator of Sarcopenia.

The triglyceride glucose (TyG) related index, a metric used to evaluate assessing insulin resistance (IR), has received limited attention in its association with sarcopenia. Our study aims to explore the predictive potential of the TyG index for sarcopenia. This study utilized data from the China Health and Retirement Longitudinal Study, a nationally representative, community-based cohort study, including a sample size of 10,537 participants aged 45 years and older. Associations between TyG related index and sacopenia was explored using multivariate logistic regression. Analysis of the predictive value of TyG related index for sarcopenia using receiver-operating characteristic curve (ROC). We evaluated the correlation between the TyG related index and the risk of sarcopenia using Cox proportional hazards models. Additionally, we utilized restricted cubic spline (RCS) regression analyses to explore the connections between the TyG-related index and sarcopenia. Logistic regression analysis showed an association between TyG (OR 0.961[0.955,0.968], P < 0.001), TyG-body mass index (TyG-BMI) (OR 0.872[0.867,0.878], P < 0.001), TyG- waist circumference (TyG-WC) (OR 0.896[0.890,0.902], P < 0.001) and sarcopenia. The results of the ROC analysis indicated that the area under the curve values for TyG, TyG-BMI, and TyG-WC were 0.659, 0.903, and 0.819, respectively. Compared to those without sarcopenia, patients with sarcopenia had a 37.7% (HR 0.623[0.502,0.774], P < 0.001), 4.8% (HR 0.952[0.947,0.958], P < 0.001), and 0.4% (HR 0.996[0.995,0.996], P < 0.001) lower risk with increasing TyG, TyG-BMI, and TyG-WC, respectively. RCS results show nonlinear relationship between TyG-BMI (P < 0.001) and TyG-WC (P < 0.001) and risk of sarcopenia. We observed a correlation between the TyG-related index and sarcopenia, with the TyG-BMI index demonstrating strong predictive capability for sarcopenia.

Prevalence and clinical correlates of impaired fasting blood glucose in children and adolescents with depressive disorder and relationship with triglyceride and high-density lipoprotein ratio.

Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents' health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People's Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43-4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11-2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders.

Triheptanoin in patients with long-chain fatty acid oxidation disorders: clinical experience in Italy.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD. METHODS: This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported. RESULTS: Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients' total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment. CONCLUSIONS: The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.

Nonlinear relationship between triglyceride-glucose index and the risk of prediabetes and diabetes: a secondary retrospective cohort study.

Background: The triglyceride-glucose (TyG) index, recognized for its cost-efficiency and simplicity, serves as an accessible indicator of insulin resistance. Yet, its correlation with the risk of prediabetes and diabetes (Pre-DM/DM) in the Chinese demographic remains uncertain. Consequently, our study explored the association between the TyG index and the development of Pre-DM/DM within the Chinese population. Methods: The retrospective cohort study was carried out utilizing data from a health screening initiative. The study included 179541 adults over 20 who underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. The correlation between the TyG index and Pre-DM/DM risk was investigated using Cox regression analysis. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore their non-linear connection. Results: The mean age of study participants was 41.18 ± 12.20 years old, and 95255 (53.05%) were male. During a median follow-up of 3.01 years, 21281 (11.85%) participants were diagnosed with Pre-DM/DM. After adjusting the potential confounding factors, the results showed that the TyG index was positively correlated with incident Pre-DM/DM (HR: 1.67, 95%CI: 1.62-1.71, P< 0.001). Additionally, a non-linear association was observed between the TyG index and the onset of Pre-DM/DM, with an inflection point identified at 8.73. Hazard ratios (HR) to the left and right of this inflection point were 1.95 (95%CI: 1.86-2.04) and 1.34 (95%CI: 1.27-1.42), respectively. Furthermore, sensitivity analyses confirmed the stability of these findings. Conclusion: The TyG index exhibited a non-linear positive relationship with the risk of Pre-DM/DM. These findings imply that maintaining the TyG index at a lower, specified threshold may be beneficial in mitigating the onset of Pre-DM/DM.

Higher triglyceride glucose-waist height ratio index is associated with higher prevalence of gallstone: a population-based study.

Background: The aim of this study is to evaluate the association between triglyceride glucose-waist height ratio (TyG-WHtR) index and the prevalence of gallstone disease (GSD), alongside the age at first gallstone surgery among adult populations within the United States. Methods: We screened participants using the National Health and Nutrition Examination Survey (NHANES). Logistic regression analysis, generalized additive modeling, smoothed curve fitting, and subgroup analysis were employed to assess the association between the TyG-WHtR index, prevalence of GSD, and the age at initial gallstone surgical intervention. Results: In this study, 3,728 participants were enrolled, among whom 395 individuals reported a prior history of GSD. The association between the TyG-WHtR index and the prevalence of GSD demonstrated a non-linear, positive association. After adjusting for all potential confounders, for each incremental unit rise in the TyG-WHtR index, there was a 47% escalation in the prevalence of GSD (OR = 1.47, 95% CI: 1.29, 1.68). Subgroup analyses indicated a more pronounced association between the TyG-WHtR index and the prevalence of GSD among individuals aged 20-80 years, females, non-Hispanic white population, non-Hispanic black population, other racial groups, and non-diabetic cohorts. Additionally, this study identified that the TyG-WHtR index may be negatively correlated with age at first surgical treatment of gallstones. Conclusion: An elevated TyG-WHtR index demonstrates a positive association with the prevalence of GSD. However, more prospective studies are needed to validate our findings.

Association Between Triglyceride Glucose Index and Chronic Kidney Disease in Normal-Weight Chinese Adults With Hypertension.

This study aimed to examine the association between the triglyceride-glucose (TyG) index and chronic kidney disease (CKD) in normotensive adults with hypertension and further investigate potential effect modifiers of this association. A total of 7975 normoweight hypertensive participants were enrolled from the Chinese H-type hypertension registry (CHHRS) cohort. The TyG index was calculated using the formula: ln (fasting triglyceride [mg/dL] × fasting plasma glucose [mg/dL])/2. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 of body surface area. Multivariate logistic regression analysis revealed a 50% increased risk of CKD (OR: 1.50, 95% CI: 1.26-1.79) for each unit increase in the TyG index. A linear dose-response relationship between the TyG index and CKD risk was observed using restricted cubic spline analysis. Compared to the first quartile of the TyG index, the fourth quartile showed a significantly higher risk of CKD (OR: 1.88; 95% CI: 1.41-2.50). Subgroup analysis identified a stronger association between the TyG index and CKD risk in males and individuals with a history of alcohol consumption (all p values for interaction < 0.05). In conclusions, the TyG index was significantly associated with an increased risk of CKD in normoweight adults with hypertension, particularly in males and those with a history of alcohol consumption.

A retrospective study utilized MIMIC-IV database to explore the potential association between triglyceride-glucose index and mortality in critically ill patients with sepsis.

Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index's prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P < 0.01) and a 79% higher risk of ICU mortality (HR 1.79 [95% CI 1.28 to 2.51], P < 0.001). Model 3 showed that ICU mortality risks for Q4, Q3, and Q2 were 240%, 75%, and 33% higher, respectively (HR 3.40 [95% CI 2.24 to 5.16], P < 0.001; HR 1.75 [95% CI 1.16 to 2.63], P = 0.007; HR 1.33 [95% CI 1.20 to 1.53], P < 0.001). RCS regression analysis identified a nonlinear association between the TyG index and mortality (overall P < 0.001; P for nonlinearity < 0.001, with an inflection point at 8.9). Subgroup analysis showed that the effect size and direction were consistent across different subgroups, suggesting the stability of the results. This study demonstrates that a higher TyG index is significantly associated with increased in-hospital and ICU mortality risk in critically ill sepsis patients, with evidence of non-linear correlation. Therefore, the TyG index helps identify the mortality prognosis of sepsis patients in the ICU.

Assessing and predicting type 2 diabetes risk with triglyceride glucose-body mass index in the Chinese nondiabetic population-Data from long-term follow-up of Da Qing IGT and Diabetes Study.

AIMS: We intended to characterize the superiority of triglyceride glucose-body mass index (TyG-BMI) in predicting type 2 diabetes mellitus (T2DM) compared with triglyceride glucose (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR). METHODS: A total of 699 nondiabetic participants in the Da Qing IGT and Diabetes Study were involved in the present analysis and classified according to the median of baseline TyG-BMI, namely the G1 (low TyG-BMI) and G2 (high TyG-BMI) groups. Information on developing diabetes was assessed from 1986 to 2020. RESULTS: During the 34-year follow-up, after adjustment for confounders, the G2 group had a higher risk of developing type 2 diabetes than the G1 group (hazard ratio [HR]: 1.92, 95% confidence interval [CI]: 1.51-2.45, p < 0.0001). Restricted cubic spline analyses showed that increased TyG-BMI was linearly related to higher risks of type 2 diabetes (p for non-linearity>0.05). Time-dependent receiver operator characteristics curves suggested that TyG-BMI exhibited higher predictive ability than TyG (6-year: area under the curve [AUC]TyG-BMI vs. AUCTyG, 0.78 vs. 0.70, p = 0.03; 34-year: AUCTyG-BMI vs. AUCTyG, 0.79 vs. 0.73, p = 0.04) and HOMA-IR (6-year: AUCTyG-BMI vs. AUCHOMA-IR, 0.78 vs. 0.70, p = 0.07; 34-year: AUCTyG-BMI vs. AUCHOMA-IR, 0.79 vs. 0.71, p = 0.04) in both short and long terms, and the thresholds of TyG-BMI to predict type 2 diabetes were relatively stable (195.24-208.41) over the 34-year follow-up. CONCLUSIONS: In this post hoc study, higher TyG-BMI was associated with an increased risk of type 2 diabetes and demonstrated better predictability than TyG and HOMA-IR, favoring the application of TyG-BMI as a potential tool for evaluating the risk of type 2 diabetes in clinical practice.