Contrast-induced acute kidney injury (CI-AKI) refers to acute kidney complications after intravenous administration of contrast agents during angiography, such as those used for enhanced CT, enhanced MRI, or vascular interventional treatment (1, 2). The new diagnostic criterion proposed by the “Kidney Disease: Improving Global Outcomes (KDIGO)” research team indicates postoperative increased serum creatinine (Scr) by ≥26.5 μmol/l (0.3 mg/dl) or by at least 50% compared to preoperative Scr (3). Despite increased awareness of CI-AKI prevention over the past decade, the incidence of CI-AKI remains relatively high. Amin (4) reported that, in 2008, the incidence of AKI, using the KDIGO definition, was 19.7% of 31,532 patients with acute myocardial infarction (AMI). The National Cardiovascular Data Registry Cath-PCI registry enrolled 985,737 patients who underwent percutaneous coronary intervention (PCI) between June 2009 and June 2011 and reported that 7.1% of these patients experienced CI-AKI with 3,005 (0.3%) requiring new dialysis (5). CI-AKI is the third leading cause of hospital-associated acute kidney injury after low perfusion-related kidney injury and drug-induced kidney injury (6). There is no effective treatment for CI-AKI because the exact pathogenesis of CI-AKI has not been fully elucidated. Therefore, screening patients with high risk factors and adopting prompt preventive strategies are very important for reducing the incidence of CI-AKI.

Diabetes mellitus (DM) is one of the primary risk factors for CI-AKI and is an essential factor in risk stratification (7). Insulin resistance (IR) is an important pathophysiological process and risk factor for T2DM (8). IR is closely related to the prevalence of chronic kidney dysfunction (9). Li et al. discovered that the incidence of CI-AKI in patients with insulin resistance was comparable to that of diabetic patients, and a logistic regression analysis showed that the insulin resistance index HOMA-IR was an independent risk factor for CI-AKI (OR = 1.39) (10). The emerging triglyceride-glucose (TyG) index demonstrated a close relationship with insulin resistance (11). As a new index for evaluating insulin sensitivity, TyG is highly correlated with the HOMA-IR assessment model and the euglycemic-hyperinsulinemic clamp gold standard experiment (12, 13). It has been reported that TyG is associated with many cardiovascular diseases, such as acute myocardial infarction (14), cardiovascular events (15), arterial stiffness (16), and coronary artery calcification (17). The TyG index is becoming a promising alternative indicator of insulin resistance due to its efficacy, simplicity and low cost. The purpose of this study was to investigate the predictive value of the TyG index for the occurrence of CI-AKI in patients with T2DM undergoing coronary angiography and to provide new insights for optimizing the CI-AKI risk assessment model.

In this study, we investigated the predictive value of the TyG index for the occurrence of CI-AKI in T2DM patients after coronary angiography. Patients in groups 2, 3, and 4 exhibited a markedly increased incidence of CI-AKI compared to those in group 1. We demonstrated, for the first time, that TyG, a biomarker of insulin resistance, is an independent risk factor for CI-AKI and has good predictive value for the diagnosis of CI-AKI. The AUC of the TyG index predicting CI-AKI reached 0.728 (95% CI = 0.691–0.761, P = 0.019), and the corresponding sensitivity was 94.7%. We provide a risk assessment model, including age, sex, hypertension, SBP, DBP, CKD, hydration, eGFR, FBG, TG, TC, and LDL-c levels and the TyG index, the AUC of which was as high as 0.820. There were no significant differences in the AUC for conventional risk models 1 and 2 (with the TyG index added) (P=0.405). The reason that the AUC was not significantly different between the 2 models is because we included 2 variables, FBG and TG levels, in conventional model 1. The TyG index is calculated using the formula ln [fasting TG (mg/dL)×FPG (mg/dL)/2]. Therefore, it is understandable that the 2 models have similar predictive value for CI-AKI. Models 1 and 2 exhibited good predictive value, and both emphasized the significance of TyG index (FBG and TG) or insulin resistance. Furthermore, the slight difference might be distinguished in larger sample sizes. The AUC for the TyG index used for predicting CI-AKI was aberrantly higher than that for the TG level (0.570), while it was statistically similar with that for the FPG level. Both the TyG index and FPG level showed fine predictive value, but model 2, which combines additional independent risk factors with a larger AUC is recommended over a model based on a single variable.

CI-AKI is a serious complication of cardiac intervention and the third leading cause of acute kidney injury in the hospital, contributing to severe short-term and long-term adverse prognosis (21). CI-AKI is an incurable disease, but adequate intravenous hydration, avoiding the use of nephrotoxic drugs, choosing low osmotic or isotonic contrast agents and reducing the amount of contrast agents are all effective preventive measures to reduce the incidence of CI-AKI (22). Therefore, prompt risk assessment and timely prevention for high-risk patients are effective ways to reduce the incidence of CI-AKI.

In Tsai’s research, eGFR >60 ml/min/1.73 m² was indicated to be normal if it was not in the setting of a unilateral kidney or in a patient with structural kidney disease (5). Referring to Tsai’s research and the CKD definition, the eGFR of the CKD patients in our research ranged from 30–60 ml/min/1.73 m². There were a total of 19 CKD (11 stage 3A and 8 stage 3B) patients in our study. As shown in Table 2 , no significant differences were found in the incidence of CKD between the 4 groups with different TyG levels, indicating preoperative eGFR level of the CKD patients did not influence the outcome in the current research. Furthermore, the incidence of CI-AKI increase was relatively flat between eGFR>60 ml/min/1.73 m² and 30<eGFR<45 ml/min/1.73 m² after coronary angiography with PCI, according to baseline serum creatinine (3). In conclusion, 19 (2.05%) patients with 30<eGFR<60 ml/min/1.73 m² did not skew the research results.

Diabetes is a clear independent risk factor for CI-AKI. Diabetic kidneys are more susceptible to the effects of hypoxia and oxidative stress that aggravates the renal damage caused by contrast agents (23). Diabetic patients with CI-AKI have a worse prognosis compared to CI-AKI patients with normal blood glucose (24). Type 2 diabetes primarily occurs because of defects in insulin secretion and insulin resistance (25). Insulin resistance is a systemic disorder affecting several insulin-regulated pathways and many organs. It is characterized by reduced insulin effects, despite increased insulin concentrations in the blood. Insulin resistance is a hallmark of metabolic syndrome and a crucial characteristic for T2DM and increases the risk of cardiovascular events (26).

A series of epidemiological investigations demonstrated the role of insulin resistance in renal insufficiency, and insulin resistance plays a role in increasing vascular permeability (27). Insulin resistance is also associated with the occurrence of early glomerular hyperfiltration and contributes to late glomerular damage in the early stages of diabetic nephropathy (28, 29). Insulin signaling exerts crucial roles in renal hemodynamics, podocyte viability, and tubular function through the insulin receptor located on renal tubular cells and podocytes. Insulin resistance-associated hyperinsulinemia is related to metabolic syndrome, inflammation, and adipocytokine disorders, which can cause glomerular damage (9). The actions of insulin on renal sodium handling are preserved during hyperinsulinemia and contribute to increasing sodium reabsorption and increasing glomerular filtration rate, eventually leading to kidney damage (30). Glomerular endothelial cell injury, mesangial cell proliferation, and thickened basement membranes associated with insulin resistance related to oxidative stress ultimately cause glomerular sclerosis and renal tubular interstitial injury, leading to renal insufficiency (31).

As an emerging hematological indicator of insulin resistance, the products of triglycerides and fasting plasma glucose produced during fasting provide promising results that can be used to assess IR (13). TyG is a simple and convenient biomarker with high stability, and research has shown that the TyG index performs better than HOMA for the estimation of IR (12, 32). TyG has been shown to increase the risk of diabetes and various cardiovascular diseases. Low S and colleagues recruited 4,109 subjects without T2DM and discovered that patients in TyG quartiles 2, 3, and 4 exhibited significantly increased risk of developing T2DM compared to those in quartile 1 (33). Kahui Park et al. demonstrated in a study involving 1,175 Korean adults that the TyG index is associated with coronary artery calcification (CAC), and the TyG index is an independent risk factor for CAC (OR = 1.82, 95% CI=1.20-2.77, P<0.01) (17). An increased TyG index was significantly associated with an increased risk of developing cardiovascular disease and is thus useful for the early identification of CVD events in high-risk individuals (34).

Hyperglycemia also increases the risk of CI-AKI (35). Yin Wenjun et al. constructed a risk prediction model of CI-AKI with an AUC of 0.907 based on 8,800 patients who underwent angiography, and for the first time, preoperative blood glucose level was included in the predictive model (36). Barbieri L first demonstrated that elevated HbA1c is associated with an increased risk for CI-AKI among patients without prediabetes undergoing coronary angiography/PCI (37). However, in this study, the TyG index was independently correlated with CI-AKI, while neither HbA1c nor FPG was an independent risk factor for CI-AKI in the patients with T2DM who underwent coronary angiology. The TyG index is expected to become a novel predictive indicator for CI-AKI, providing new insight for CI-AKI risk stratification.

The current study demonstrates that a high TyG index is closely correlated with a higher incidence of CI-AKI in patients with T2DM undergoing coronary angiology, representing an independent risk factor for CI-AKI. The TyG index has enhanced predictive value, and furthermore, it attracted our attention because of its simplicity, convenience and low cost and because it might provide new insights into risk stratification in clinical practice.

The datasets generated for this study are available upon request sent to the corresponding author.

The studies involving human participants were reviewed and approved by the Research Ethics Committee of the Affiliated Zhongda Hospital of Southeast University. The patients/participants provided their written informed consent to participate in this study.

CT, GY, and YQ contributed to the conception and design of the study. YHQ and HT collected the data, and YHQ, DW, YQ, EL, and JH participated in the data analysis and interpretation. YHQ wrote the manuscript with contributions from all authors. All authors contributed to the article and approved the submitted version.

This work was supported by the National Natural Science Foundation of China (grant no. 81970237, 81600227).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.