To our knowledge, this study is the first to investigate the relationship between TyG index and all-cause mortality in patients with sepsis. This study found a significant association between elevated TyG index and increased in-hospital mortality in patients with sepsis. This conclusion is consistent with her ICU and her 28-day mortality rates in sepsis patients, which showed a consistent linear relationship. This association remained robust even after adjusting for multiple clinical and laboratory variables. Our results extended the application of the TyG index to the area of cardiovascular disorders and demonstrated its potential value as a decision-making tool for clinicians managing septic patients.
In recent years, the TyG index has been proposed as a potential marker for metabolic disorders, atherosclerosis, cardiovascular diseases, and coronavirus disease (COVID-19). [24,25,26,27]. Numerous clinical studies have investigated the association between elevated TyG index and increased morbidity and mortality associated with critically ill patients and infections in various populations. Yang et al. We found that the TyG index was an independent risk factor for in-hospital and ICU mortality in patients after cardiac arrest. [7]. Lee et al. We observed that the TyG index may be useful in predicting short-term functional outcomes in severe stroke patients undergoing reperfusion therapy. [28]. Furthermore, for individuals with coronary artery disease, the TyG index may contribute to the prediction of adverse cardiovascular events. [29, 30]. In the general population, a high TyG index has been found to be associated with an increased incidence of respiratory symptoms, increased risk of chronic lung disease, and decreased lung function. [31]. Collectively, these studies suggest a possible association between her TyG index and clinical outcomes in critically ill and infection-related patients. Other studies have reported that each unit increase in TyG index increases the risk of in-hospital mortality in critically ill patients by almost 30% or more. [8, 9]. We observed that for each unit increase in the TyG index, the risk of in-hospital death in sepsis patients increased by 44.0%. The conclusions of our study are consistent with previous studies and show that there is an association between elevated TyG index and increased mortality.
Our results suggest an association between high TyG index and sepsis severity and outcome. Sepsis can cause insulin resistance and disruption of lipid metabolism, with uncontrolled hyperglycemia and blood glucose fluctuations during the acute phase of sepsis. The prognosis of sepsis is closely related to the severity of the inflammatory response, and the inflammatory response is significantly correlated with insulin resistance. Our results show that the TyG index is positively correlated with disease severity scores. The TyG index reflects the disease severity in sepsis patients and provides insights that can contribute to the clinical management of sepsis. Clinicians need to be aware of their patients’ glycemic control and monitor changes in insulin resistance indicators.
The exact biological mechanism underlying the relationship between TyG index and sepsis prognosis remains unclear. The TyG index is associated with insulin resistance (IR), and it has been widely proven that insulin resistance is closely associated with endothelial dysfunction, oxidative stress, immune dysregulation, coagulation imbalance, and inflammatory responses . [32,33,34], all of which are also closely related to the occurrence and progression of sepsis. From baseline data, significant differences in SOFA scores were observed between patients in different TyG index groups, indicating a close association between TyG index and disease severity. Changes in insulin resistance during the acute phase of sepsis may reflect the inflammatory state or severity of sepsis. A potential explanation for the role of the TyG index as an indicator of cardiovascular disease could be that the TyG index serves to reflect the patient’s IR. In turn, IR may contribute to the development of cardiovascular diseases by increasing vascular stiffness and reducing the bioavailability of nitric oxide (NO). [35, 36]. Elevated TyG index is associated with cardiovascular disease, and the presence of cardiovascular disease in sepsis is a risk factor contributing to adverse patient outcomes. Although cardiovascular disease was present in groups with different HisTyG index levels in this study, no differences were observed.
In our study, in a sensitivity analysis, the linear relationship between TyG index and in-hospital mortality in patients with sepsis remained consistent in younger age groups, female patients, patients with lower BMI, those without hypertension, and those without congestive heart failure. It turned out to be. . This result may be due to the fact that older age, male gender, high BMI, and hypertension are traditionally recognized as unfavorable risk factors for sepsis prognosis. Additionally, factors such as gender, obesity, and cardiovascular disease may contribute to insulin resistance, potentially underestimating the association between TyG index and sepsis outcome. On the other hand, in the subgroup analysis, we observed that the results were not statistically significant after stratifying by SOFA score and gender for 28-day mortality and her ICU mortality. After stratified analysis, the sample size decreases, leading to a decrease in effect size. This could be one of the reasons for the non-significant results. However, the consistent direction of all results indicates the stability and reliability of the central results. In patients with a perfect SOFA score, the relationship between TyG index group and in-hospital ICU and her 28-day mortality remained stable. In Cox regression analysis, the relationship between her 28-day mortality and his 90-day mortality in the TyG index group was consistent with the primary outcome. Furthermore, we performed feature analysis utilizing SHAP and Brouta plots to assess the importance of TyG index as a feature within the outcome prediction model. Therefore, in the future, a machine learning prognostic model for sepsis may be established by focusing on the TyG index.
However, it is important to recognize the limitations of this study. First, our analysis is retrospective and based on observational data, which precludes the conclusive establishment of causality. Nevertheless, we employ a variety of rigorous statistical methods to produce robust and reliable results. Second, the TyG index is not dynamically monitored, and sepsis itself may affect lipid metabolism and blood glucose fluctuations. The TyG index obtained from your initial glucose and triglyceride measurements may not be a comprehensive representation of your body’s insulin resistance. Third, several confounding factors such as metabolic syndrome parameters, Acute Physiology and Chronic Health Evaluation II (APACHE II), nutritional status parameters, and inflammatory markers were not fully considered. This may affect the results. Fourth, clinicians have followed different guidelines with different definitions of sepsis from 2008 to 2019, and this may have influenced the study results. Fifth, when patients receive enteral or parenteral nutrition, it can affect lipid and blood glucose levels, which can lead to an increase in the TyG index. However, our study includes a large sample size, which may reduce this effect. Further studies are needed to investigate the main mechanisms of insulin resistance in sepsis patients.
