In this study we included patients with type 2 diabetes and no symptom or history of cardiovascular disease but with rather poor control of hypertension and lipid disorders. TyG index correlated with HOMA-IR. Patients with higher TyG index had more metabolic disorders. More than one third of our patients had coronary stenoses on CCTA and 19% had severe CS (≥ 70%). Patients with severe CS had higher TyG index and HOMA-IR. The prevalence of CS ≥ 50% and ≥ 70% was higher in the high tertile of TyG index but did not differ across the tertiles of HOMA-IR. TyG index significantly predicted the presence of CS ≥ 70%. In addition, we showed for the first time in an asymptomatic population that the number of stenosed coronary arteries and the degree of coronary stenosis were associated with high TyG index levels. TyG index ≥ 10 was significantly associated with a 3- to 5-fold greater risk of higher number of stenosed coronary arteries and of more severe coronary stenoses, and these risks remained mostly significant after adjustment for confounding factors. Our results suggest that in patients with type 2 diabetes TyG index may be considered as a marker of insulin resistance and could identify patients with high coronary risk.
TyG index as a marker of insulin resistance and metabolic syndrome
TyG index, a composite indicator based on triglyceride level and fasting plasma glucose value, was shown to correlate with insulin resistance as assessed by hyperinsulinemic euglycemic clamp or HOMA-IR (13-15) and may thus be used as a surrogate marker of insulin resistance. When compared to clamp, TyG index could even perform better than HOMA-IR (25). TyG index was also reported to be a marker of metabolic disorders (7,14,26) and a good predictor of incident type 2 diabetes (27-29). In our population of patients with type 2 diabetes, higher TyG index was strongly associated with higher HOMA-IR and more pronounced metabolic disorders including higher BMI, increased waist circumference, total cholesterol, triglycerides, LDL-cholesterol, non-HDL cholesterol, plasma glucose and HbA1c levels, lower HDL-cholesterol levels and also less physical activity. This index was not associated with current glucose-lowering treatments except for α-glucosidase inhibitors (only 30 patients on this treatment) nor with lipid lowering treatment, noting that none of our patients was on fibrate, which might have altered TyG index. Interestingly, TyG index calculation effectively led to metabolic syndrome diagnosis with rather good performances when using a threshold at 9.145.
TyG index as a marker of atherosclerosis and cardiovascular complications
Several studies suggest that TyG index might be recognized as a risk factor for cardiovascular complications and a marker of atherosclerosis. TyG index was shown to be an independent predictor of cardiovascular events in a healthy population (16) and to be associated with a higher incidence of cardiovascular outcomes in patients with stable coronary artery disease (30) including those with type 2 diabetes (31), in patients with non-ST elevation acute coronary syndrome (32) and in those with acute ST-elevation myocardial infarction after percutaneous coronary intervention (33). This index was reported to be a better marker than HOMA-IR for subclinical carotid atherosclerosis and arterial stiffness in the general population (34-36) and in lean postmenopausal women (17). In a healthy population TyG index was more independently associated with coronary artery calcifications than was HOMA-IR (26). Elevated TyG index was also shown to be an independent predictor of progression of coronary calcifications (37).
Cardiovascular risk in contemporary South-Asian countries
Cardiovascular disease is becoming a major cause of deaths in Vietnam like in other low-middle income countries. In the setting of acute myocardial infarction, the incidence of in-hospital death rates is higher in patients with multiple cardiac comorbidities (38) with a need to improve guideline adherence (39). The proportion of patients with diabetes and silent coronary artery disease is expected to be greater than in higher income countries. In the present study, CCTA detected coronary stenoses ≥ 50% in 36% and ≥ 70% in 19% of the patients. In two previous studies which similarly performed CCTA in asymptomatic individuals, the proportion of patients with CS ≥ 70% was found lower: 6.3% in a US population of patients with type 1 or type 2 diabetes considered to be at high cardiovascular risk (6) and 12.3% in a Korean population of patients with type 2 diabetes (7). Compared to the latter study, our population had some similarities but the risk was greater because blood pressure, triglycerides and LDL-cholesterol levels were higher, and TyG index was also higher. The levels of these risk factors were clearly above target values according to the recent guidelines (1).
TyG index is an independent marker of the severity of silent coronary disease
In our study, TyG index was associated with an increased risk of CS on CCTA, consistently with previous reports (7). Additionnally, since diabetes is associated with an increase in the extension and severity of coronary artery disease, we evaluated for the first time the severity of CS and found that TyG index ≥ 10 was associated with an increased number of stenosed vessels and more severe stenosis. This risk was independent of diabetes duration, BMI, systolic blood pressure, HbA1c, eGFR, physical activity and smoking. This result is consistent with a previous study in patients with non-ST elevation acute coronary syndrome observing an independent association of TyG index with the number of stenosed coronary arteries and the SYNTAX score (32). This suggests that insulin resistance as expressed by TyG index may contribute to atherosclerosis in addition to cardiovascular risk factors.
However the association of TyG index with more severe coronary disease remained significant after further adjustment on logHOMA-IR, suggesting that both metabolic disorders expressed by TyG index may play a role in coronary atherosclerosis. Improved glycemic control is expected to reduce TyG index level and may contribute to reduce cardiovascular outcomes in patients with type 2 diabetes (40). Whether or not triglycerides are involved in the atherosclerotic process is still debated. Some data strongly suggest a relation between elevated triglyceride levels and cardiovascular disease (41-42) with a residual cardiovascular risk associated with triglycerides in patients with type 2 diabetes who have reached their LDL-cholesterol target (43,44). A major role of the retention of cholesterol-rich and triglyceride-rich apoB-containing remnants within the arterial wall is to be considered in the pathogenesis of atherosclerosis (45).
In subgroup analyses we observed that TyG index was associated with an increased risk of CS ≥ 70% in patients on statin or antiplatelet therapy. This suggests that TyG index might account at least partly for the residual risk that remains despite these treatments. Thus, triglyceride level lowering appears as an additional target in patients at high cardiovascular risk (1,43, 46-49).