In our present study, we retrospectively investigated the predictive significance of IR assessed by TyG index for adverse prognosis in patients with T2DM and NSTE-ACS who were treated with PCI. The major findings are listed as follows: (1) the TyG index was significantly correlated with variety of risk factors for cardiovascular disease; (2) compared to participants with lower TyG index, those with higher TyG index had an apparently higher incidence of primary endpoint.; (3) the increased level of TyG index was a strong indicator of worse prognosis in the study population, even after adjustment of confounding risk factors; (4) the addition of TyG index to the baseline risk model including traditional risk factors significantly promoted the ability of risk stratification.
T2DM has been widely recognized as the most significant risk factors for cardiovascular disease and it is very common for patients with ACS combined with T2DM. Certain studies have demonstrated that T2DM is significantly associated with higher prevalence of CAD, more complex coronary lesions and adverse prognosis [4–6] and the association has been shown to be mediated primarily by IR [26]. It has been proved that IR is significantly related to the development and progression of coronary atherosclerosis [7, 8]. Therefore, for patients with or at high risk of CAD, quantitative assessment of the extent of IR is of great clinical importance for risk stratification and prognosis prediction. The euglycemic-hyperinsulinemic clamp has been acknowledged as the gold standard method for the diagnosis of IR by previous studies [27]. However, this method is relatively time-consuming, expensive and complicated to operate, which makes it comparatively difficult to be applied in real-world clinical practice. Homeostasis model assessment of IR (HOMA-IR), which is calculated by fasting insulin and glucose, has been one of the commonly used method for the assessment of IR in current clinical applications [27]. However, the insulin concentration is not routinely measured in clinical practice, which makes HOMA-IR inappropriate for extensive clinical application. Based on these, a surrogate marker of IR named TyG index derived from commonly used clinical indicators (fasting TGs and glucose) has been proposed and showed to be well related to the euglycemic-hyperinsulinemic clamp and HOMA-IR [10, 28, 29]. And studies even showed that the TyG index may have a better performance on the prediction of IR and atherosclerosis compared with HOMA-IR [30, 31].
Previous studies have demonstrated that IR evaluated by TyG index is strongly related to the incidence of diabetes and prediabetic status, suggesting that TyG index may be a considerable predictor for early identifying individuals at high risk of developing diabetes and prediabetes, even performs better than other risk factors such as FBG and weight gain [13–15, 32, 33]. Studies also showed that elevated level of TyG index is prominently associated with an increased risk of developing cardiovascular disease including CAD and ischemic stroke, which suggests evaluation of TyG index might be helpful for identifying people who is susceptible to cardiovascular disease, despite existence of traditional cardiovascular risk factors or not [16, 17, 34–36]. And for patients with stable CAD, TyG index has been demonstrated to be positively related to future adverse clinical outcomes, indicating that TyG index may play an important role in the prediction of clinical prognosis in patients with stable CAD [37, 38]. The clinical significance of TyG index has been increasing as the adverse effects of it on individuals with or at high risk of cardiovascular disease have been elucidated. Evaluation of TyG index may have great clinical importance on risk stratification and therapeutic individuation for these patients.
Several studies have shown that there is an important correlation between TyG index and clinical prognosis in patients with ACS. Study from Mao et al [39] revealed that the level of TyG index is strongly associated with the complexity of coronary lesions and the incidence of future adverse cardiovascular event during a 12-month of follow-up in patients diagnosed with NSTE-ACS. Another observational study from Luo et al [40] assessing the predictive potential of TyG index for 1-year prognosis suggested that the increased TyG index might be an effective indicator of worse prognosis in patients with ST-segment elevation myocardial infarction (STEMI) who were treated with PCI. However, no adjustment was made for the presence of diabetes or not in multivariate analysis in both of the former studies, and neither of them evaluate whether the prognostic impact of TyG index varied among different glycometabolic status. What’s more, the former studies only confirmed the effect of TyG index on poor prognosis from a 12-month follow-up, which is relatively insufficient to evaluate the long-term prognostic impact of TyG index. Ma et al [41] evaluated the predictive significance of TyG index in participants with T2DM and ACS undergoing PCI and showed that the TyG index was the independent predictor of adverse clinical outcomes. However, whether the addition of TyG index has an incremental effect on predicting adverse cardiovascular prognosis on the basis of traditional risk factors is not confirmed. Our present study revealed the significant prognostic impact of TyG index and its incremental effect on risk stratification in diabetic patients with NSTE-ACS undergoing PCI, which makes the study be great agreement and complement to previous literatures.
The potential mechanism inducing the association of IR presented by TyG index with development and progression of cardiovascular disease remains uncertain, several speculations summarize as follows. (1) It has been demonstrated that TyG index is closely related to traditional risk factors for cardiovascular disease such as hypertension [42] and renal insufficiency [43]. In the present study, participants with higher TyG index exactly tended to combine with more severe and complex clinical conditions in terms of BMI, blood pressure, lipid profiles and coronary lesions, and correlation analysis also showed that TyG index is positively related to multiple risk factors for cardiovascular disease. (2) Study have shown that FBG mainly reflects IR from liver, whereas fasting TGs mainly reflects IR from adipose cell [44]. Therefore, it can be concluded that TyG index may reflect IR from two aspects and thus be closely related to IR, which has been widely demonstrated to have significant relationship with endothelial dysfunction, oxidative stress, cardio-vascular remodeling, coagulation imbalance and inflammation response [45, 46]. Indeed, a positive association between TyG index and hs-CRP levels was confirmed in the present study. (3) Certain studies have also identified an important correlation between TyG index and coronary artery calcification [47], which may be another potential mechanism.
Since adverse prognostic impacts of IR on individuals with CAD have been elucidated by previous studies, taking assessment and intervention of IR into long-term management strategies may be beneficial for patients with CAD. However, the relative lack of research about intervention on IR in patients with CAD makes it uncertain whether intervention of IR is necessary for the management of such patients. Former studies have shown that whole-grain consumption plays a significant protective role on IR and inflammatory markers [48, 49]. However, a recent systematic review of 9 RCTs indicated that there is insufficient evidence on the effect of whole-grain diets on cardiovascular outcomes or major cardiovascular disease risk factors [50]. This may be partly attributed to the fact that the association between whole-grain consumption and IR is partially mediated by adiposity[49]. Our present study also revealed that the predictive value of IR presented by TyG index seemed to be more prominent in patients BMI > 28 kg/m2 [HR (95% CI): BMI > 28 kg/m2 4.625 (2.863–7.471) vs. BMI ≤ 28 kg/m2 2.355 (1.749–3.170), P for interaction = 0.044]. Further specific-designed studies are required to determine whether interventions of IR assessed by TyG index have a positive impact on improving clinical prognosis in this population.
This study confirmed the predictive value of IR presented by TyG index for adverse prognosis in a cohort including patients with T2DM and NSTE-ACS who were treated with PCI, which indicates that TyG index can be an available predictor in clinical practice and has a positive effect on more comprehensive risk evaluation and stratification on the basis of traditional risk factors in this selected population. Meanwhile, some limitations of the study should be recognized. (1) This study is a single-center, retrospective, observational study, which may weaken the power of the results. (2) The TyG index was assessed only once at admission. The changes of TyG index during the follow-up period, which may have better prediction value for adverse prognosis, were not assessed in our study. (3) A large proportion of participants received lipid-lowering therapy, which may have potential impact on the TyG index and the study results. (4) Nearly all of the study population is Chinese patients. The results should be cautiously interpreted and expanded to Western population as differences in metabolic levels exist among different races. (5) It is hard to rule out that some patients may be complicated with undiagnosed systemic diseases, such as occult malignancies, which may have impact on the assessment of prognosis. (6) The HOMA-IR was not calculated in the present study, so the comparison between TyG index and HOMA-IR is lacking.