Tao et al.

Cardiovascular Diabetology (2022) 21:68

https://doi.org/10.1186/s12933-022-01511-x Cardiovascular Diabetology

REVIEW Open Access

Triglyceride‑glucose index as a marker

in cardiovascular diseases: landscape
and limitations
Li‑Chan Tao1†, Jia‑ni Xu1†, Ting‑ting Wang1, Fei Hua1* and Jian‑Jun Li2*

Abstract
The triglyceride-glucose (TyG) index has been identified as a reliable alternative biomarker of insulin resistance (IR).
Recently, a considerable number of studies have provided robust statistical evidence suggesting that the TyG index
is associated with the development and prognosis of cardiovascular disease (CVD). Nevertheless, the application of
the TyG index as a marker of CVD has not systemically been evaluated, and even less information exists regarding
the underlying mechanisms associated with CVD. To this end, in this review, we summarize the history of the use of
the TyG index as a surrogate marker for IR. We aimed to highlight the application value of the TyG index for a variety
of CVD types and to explore the potential limitations of using this index as a predictor for cardiovascular events to
improve its application value for CVD and provide more extensive and precise supporting evidence.
Keywords: Triglyceride-glucose index, Insulin resistance, Cardiovascular disease

Introduction identifying persons at early risk for CVD will have

Cardiovascular disease (CVD) is a leading cause of mor- remarkable clinical significance for improving risk strati-
bidity and mortality worldwide, posing serious public fication and therapeutic management.
health challenges and placing an economic burden on Insulin resistance (IR) is a state of decreased sensitiv-
patients [1]. Although several risk factors for CVD have ity and responsiveness to the action of insulin and has
been established, including age, male sex, obesity, hyper- bee identified as a hallmark of T2DM, even preceding
tension, hypercholesteraemia, and diabetes, recent stud- diabetes for several years [5]. There has been increas-
ies have demonstrated that some individuals without ing evidence demonstrating that IR and related disor-
these risk factors may also develop CVD [2, 3]. Addition- ders contribute to the development of CVD in diabetic
ally, despite the development of advanced techniques and as well as nondiabetic subjects [6]. It is well known that
the popularization of primary and secondary prevention individuals with IR are predisposed to developing several
measures, patients with CVD remain at increased risk of metabolic disorders, such as hyperglycaemia, dyslipidae-
recurrent adverse cardiovascular events [4]. Therefore, mia, and hypertension, all of which are strongly associ-
ated with poor outcomes of CVD [7]. Thus, IR has been
† regarded not only as a pathogenic cause but also as a pre-
Li-Chan Tao and Jia-ni Xu are contributed equally to this work
dictor of CVD in both general populations and subjects
*Correspondence: [email protected]; [email protected]
with diabetes. Therefore, developing convenient and reli-
1
The Third Affiliated Hospital of Soochow University, Juqian Road, able screening tools to detect IR and predict cardiovascu-
Changzhou 213000, China
2
State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, lar risks is of particular importance.
National Center for Cardiovascular Diseases, Chinese Academy of Medical Currently, there are no specific methods for the accu-
Sciences and Peking Union Medical College, No 167 BeiLiShi Road, rate determination of IR. The gold standards of the
XiCheng District, Beijing 100037, China

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Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 2 of 17

euglycemic insulin clamp and intravenous glucose toler- healthy individuals, the TyG index was found to be a bet-
ance testing are invasive and expensive; although they ter surrogate (sensitivity 84.0% and specificity 45.0%) to
are used in academic studies, they are not applied in identify IR than the HOMA-IR index [9]. However, its
clinical practice [8]. The homeostasis model assessment- low specificity (45.0%) and potentially high proportion
estimated insulin resistance (HOMA-IR) index, a means of false-positive tests has limited the widespread use of
for detecting β-cell function and IR, is widely used at the TyG index in screening for IR. In 2010, a cross-sec-
present, but it has limited value in subjects receiving tional study involving 99 individuals with various degrees
insulin treatment or those who do not have functioning of body weight and glucose tolerance was performed
beta cells [8]. To address this limitation, the triglyceride- by Guerrero-Romero et al., and they identified the TyG
glucose (TyG) index has been developed and was shown index as an optimal tool for the assessment of IR, showing
to be superior to HOMA-IR in assessing IR in individu- high sensitivity (96.5%) and specificity (85.0%) compared
als with and without diabetes [9]. According to previous to the gold standard, the euglycemic-hyperinsulinaemia
studies, this simple, convenient, and low-cost surrogate clamp test [11]. Furthermore, in a cross-sectional study
does not require insulin quantification and may be used of 82 Brazilian subjects with T2DM or normal glucose
in all subjects regardless of their insulin treatment status tolerance conducted in 2011, the TyG index was con-
[10]. Furthermore, recent studies have demonstrated that firmed to be a better marker for estimating IR than the
the TyG index is an independent predictor of prognosis HOMA-IR index (area under the ROC curve (AUC): TyG
in diabetic or nondiabetic patients with CVD, suggesting index: 0.79, HOMA-IR index: 0.77) [12]. However, since
its potential clinical utility in predicting cardiovascular both studies had small sample sizes, the results were not
risk. fully convincing.
In this review, we systemically describe the history of Since then, the TyG index has been proven to be a reli-
the TyG index as a marker for IR. We will also discuss able and accessible index for evaluating IR in high-risk
recently published literature that has helped to shed light individuals by large clinical studies. IR plays a crucial
on the application value of the TyG index in a variety of role in the development of impaired glucose tolerance
CVD settings, as well as its potential underlying mecha- and diabetes mellitus (DM). In 2014, a study by Lee et al.
nisms associated with CVD. Additionally, the limitations enrolled a total of 5,354 middle-aged nondiabetic Kore-
of the TyG index in predicting CVD are also discussed. ans for long-term follow-up to assess diabetes status.
They found that the risk of diabetes onset in the highest
Methods quartile of the TyG index was more than fourfold higher
This systematic review examined the application value of than that in the lowest quartile (relative risk, 4.095; 95%
the TyG index in a variety of CVD types. Study selection CI 2.701–6.207), suggesting that the TyG index might
included cross-sectional, case–control, or retrospective be a useful marker for identifying subjects at high risk
studies involving clinical populations with different CVD of developing diabetes. In addition, this study revealed
phenotypes. There were no language or time restrictions that the predictive power of the TyG index was better
for eligible studies. The electronic databases PubMed and than that of the HOMA-IR index for evaluating IR [13].
Web of Science were used. The search terms used were However, the lack of positive comparisons for diagnos-
“TyG index” OR “triglyceride-glucose index” AND “coro- ing DM limited their conclusions regarding the reliabil-
nary artery disease” OR “acute coronary syndrome” OR ity of the TyG index in predicting the occurrence of DM.
“in-stent restenosis” OR “arterial stiffness” OR “coro- Then, in 2016, a study by David et al. revealed that the
nary artery calcification” OR “heart failure”. Screening TyG index had better predictive power (AUC: 0.75, 95%
of the retrieved titles and/or abstracts was performed CI 0.7–0.81) in diagnosing subjects with DM than fasting
in duplicate using Endnote Software, Version X8, and blood glucose (FBG) measurement (AUC: 0.66, 95% CI
eligible studies were identified. Two authors (Li-chan 0.60–0.72) and TG levels (AUC: 0.71, 95% CI 0.65–0.77)
Tao and Jia-ni Xu) retrieved the full texts of these stud- among 4820 individuals [14]. Thus, the TyG index may
ies and assessed them for eligibility. Disagreements were help to identify individuals at risk of developing DM in
resolved through discussion. the future so that early interventions can be provided.
In addition to DM, IR is also a significant hallmark of
History of the use of the triglyceride‑glucose index obesity, hypertension, dyslipidaemia (hypertriglyceri-
The TyG index, calculated as TyG index = ln [Fasting tri- daemia and decreased high-density lipoprotein (HDL)),
glyceride (mg/dl) × fasting glucose (mg/dl)]/2, is a com- as well as other metabolic syndrome (MetS) symptoms
posite indicator composed of fasting triglyceride (TG) [15, 16]. These metabolism-related components have
and fasting glucose (FG) levels. It was first proposed been proven to be independent risk factors for CVD
in 2008. In a large cross-sectional study of apparently [17–19]. As a useful surrogate of IR, the TyG index has
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 3 of 17

been gradually linked to the development of CVD and

poor outcomes. Using a large sample from the Vascular
Metabolic CUN cohort (VMCUN cohort) with a median
period of 10 years of follow-up, Laura et al. first suggested
a positive association between the TyG index (AUC:
0.708, 95% CI 0.68–0.73) and CVD events, including cor-
onary heart failure (CHD), cerebrovascular disease, and
peripheral arterial disease, independent of confounding
factors[20]. Since then, the relationship between the TyG
index and different types of CVD has been consecutively
revealed (Fig. 1).

TyG index in cardiovascular diseases (Fig. 2,

Table 1)
Stable coronary artery disease Fig. 2 The application of triglyceride-glucose (TyG) index in
Coronary artery disease (CAD) is one of the main causes cardiovascular diseases. TyG: triglyceride-glucose index
of cardiovascular-related death. Although advanced ther-
apeutics, including optimal drug strategies and revas-
cularization, have effectively decreased the incidence lesions. Particularly, the improvement in the AUC value
of chest pain, patients with CAD still have an increased for the evaluation of less developed collateralization was
risk of experiencing major adverse cardiovascular events most significant after adding the TyG index to the base-
(MACEs) [21]. Consistent clinical data have suggested line model [24], providing novel information regarding
that an elevated TyG index is positively associated with the relation of TyG to clinical outcomes in patients with
poor outcomes in patients with CAD. A nested case– CAD (see Table 1).
control study enrolled 1282 T2DM patients with new- In addition to the association with prognosis in patients
onset stable CAD and revealed that an increased TyG with established CAD, the TyG index has also been used
index was associated with an increased risk of major to identify asymptomatic patients with a high risk of
adverse cardiovascular and cerebral events (MACCEs) atherosclerosis. Lee et al. enrolled a total of 888 asymp-
after adjusting for confounding risk factors (HR: 1.693, tomatic adults with T2DM but without previous CAD
95% CI 1.238–2.316). Moreover, the addition of the TyG to evaluate coronary artery stenosis (CAS) by coronary
index to a Cox model containing glycated haemoglobin computed tomographic (CT) angiography and found
(HbA1c) was found to increase the predictive value for that a higher TyG index was associated with an increased
MACCEs [22]. A study by Jin et al. further confirmed the risk of CAS, similar to old age, male sex, poor glycaemic
prognostic value of the TyG index in patients with sta- control, a longer duration of diabetes, and no statin use.
ble CAD [23]. In addition, a single-centre observational Moreover, a higher TyG index was identified as an inde-
study conducted by Gao et al. with a relatively large num- pendent risk factor for CAD (OR: 3.19, 95% CI 1.371–
ber of patients revealed the value of determining the TyG 7.424) [25]. A study by Thai et al. confirmed the role of
index (ORs: 1.59 and 5.72 in the T2 and T3 groups com- the TyG index in identifying diabetic subjects at high
pared with the first tertile group) in patients with totally risk of CAD in Vietnam. They found that the number of
occluded coronary vessels over 3 months, namely, CTO narrowed coronary arteries and the degree of coronary

Fig. 1 The useful history of triglyceride-glucose index (TyG). TyG: triglyceride-glucose index; IR: insulin resistance; DM: diabetic mellitus; FBG: fasting
blood glucose; CVD: cardiovascular disease
Table 1 Characteristics and results of studies regarding TyG index in cardiovascular diseases
Author, year, and country Study design and population Outcomes evaluated and Adjusted variables Key findings
evaluation methods

Stable Coronary artery disease

Jin, 2018, China [22] Case–control, 1282 T2DM with new- Incidence of MACCEs during follow up Age, sex, body mass index, hyperten‑ TyG index was associated with
onset, stable CAD sion, family history of CAD, smoke, increased risk of MACCEs (HR: 1.693,
HDL-C, non-HDL-C, creatinine, UA, 95% CI: 1.238–2.316)
hsCRP, Gensini score
Tao et al. Cardiovascular Diabetology

Jin, 2018, China [23] Case–control, 3745 patients with Incidence of CVEs BMI, LVEF, hypertension, DM, UA, TyG index was positively associ‑
stable CAD smoke, hsCRP, HDL-C, LDL-C ated with CVES (HR: 1.364, 95% CI:
1.100–1.691)
Gao, 2021, China [24] Observational study, 1093 CAD Coronary collateralization grading Age, sex, BMI, hypertension, hypercho‑ TyG index was correlated with the
patients with CTO lesion evaluated by Rentrop score lesterolemia, T2DM, smoke, stroke, UA, occurrence of impaired collateralization
monocyte count, hsCRP (OR: 1.59–5.72) in the T2 and T3 group
(2022) 21:68

compared with the first tertile group

Lee, 2016, Korea [25] observational Study, 888 asympto‑ CAS evaluated by coronary CT angiog‑ Age, sex, glycemic control, blood pres‑ TyG index was an independent
matic adults with T2DM raphy sure, LDL-C, medication risk factor for CAS (OR:3.19, 95% CI:
1.371–7.424)
Si, 2021, China [79] Observational study, 697 asympto‑ CACS evaluated by coronary CT Age, smoke, hypertension, DM, LDL-C TyG index was an independent risk
matic patients angiography factor for CAD (OR:2.007, 95% CI:
1.066–3.780)
Thai, 2020, Vietnam [26] Cross-sectional observational study, CAS evaluated by coronary CT angiog‑ Duration of diabetes, BMI, eGFR, TyG index threshold at 10 resulted in
166 patients with T2DM raphy physical activity, smoke, HbA1c, blood 57% sensitivity and 75% specificity for
pressure predicting the presence of CS ≥ 70%
Park, 2020, Korea [29] Retrospective, observational study, CAS evaluated by coronary CT angiog‑ Age, sex, blood pressure, BMI, LDL-C, TyG index had an incremental impact
1250 asymptomatic individuals with‑ raphy HDL-C, UA on CAD (OR: 1.473, 95%CI: 1.026–2.166)
out traditional CVRFs
Silva, 2019, Brazil [80] Observational study, Evaluation of risk factors for CAD Sex, age, medication, presence of TyG index was positively associated
2330 at least had one CVD in the last disease history with a higher prevalence of sympto‑
10 years matic CAD
Yang, 2021, China [81] Prospective observational study, 5489 Incidence of MACCEs during follow up Age, sex, previous PCI/CABG, LVEF, TyG index was not independently
nondiabetic patients after PCI HbA1c, TG, hsCRP related to MACE for nondiabetic
patients who underwent PCI (HR: 0.77,
95%CI 0.56–1.16)
Si, 2021, china [82] Observational study, 680 CAD with Identification of risk factors for CAD BMI, smoke, blood pressure, DM, TyG index was an independent risk fac‑
T2DM, 985 non-CAD without T2DM with T2DM ischemic stroke tor for CAD with T2DM (OR:2.641, 95%
CI: 1.154–6.045)
Chen, 2022, China [83] Observational study, Incidence of MACCEs during follow up CKD, preoperative LVEF, insulin TyG index was significantly and
1578 diabetic patients with OPCABG dependence, LDL-C, HDL-C, extent of positively associated with MACCEs
CAD, left main disease, use of arterial after OPCABG in patients with T2DM
graft, complete revascularization, use (OR:2.133, 95% CI: 1.347–3.377)
of IABP
Page 4 of 17
Table 1 (continued)
Author, year, and country Study design and population Outcomes evaluated and Adjusted variables Key findings
evaluation methods

Acute coronary syndrome

Wang, 2020, China [32] Retrospective, observational study, New-onset MACEs during 3-year Age, sex, smoke, previous MI and TyG index was an independent
2531 ACS patients with diabetes follow up CABG, BMI, LVEF, multi-vessel disease, predictor of MACEs (HR:1.455, 95% CI:
left main disease, HbA1c, hsCRP, statin 1.208–1.753)
and insulin use
Tao et al. Cardiovascular Diabetology

Luo, 2019, China [33] Retrospective, observational study, Incidence of MACCEs during follow up Age, blood pressure, smoke, platelet TyG index was positively associated
1092 STEMI patients counts, albumin, HbA1c, UA, eGFR, with an increased risk of MACCEs
three-vessel disease, number of stents (HR:1.529, 95% CI: 1.001–2.061)
Mao, 2019, China [34] Observational study, Incidence of MACEs during follow up Age, Mets, LDL-C, HDL-C, eGFR, Killip TyG index was an independent predic‑
438 patients with NSTE-ACS class, GRACE score, CRP tor of the occurrence of the MACEs
(HR:1.878, 95% CI: 1.130–3.121)
(2022) 21:68

Zhang, 2022, China [35] Observational study, Incidence of MACEs during follow up Multi-vessel disease, PCI/CABG TyG index was positively associated
1655 nondiabetic patients with ACS with revascularization (HR: 1.67, 95% CI:
with LDL-C < 1.8 mmol/l 1.02–2.75)
Drwita, 2021, Poland [84] Observational study, 1340 nondiabetic Incidence of MACEs during1-yaer CAD, eGFR, LDL-C, TC TyG index was not independently
patients with AMI follow up related to MACE for nondiabetic
patients who underwent PCI
Gao, 2021, China [36] Prospective, observational study 1179 Incidence of MACEs during follow up Age, sex, MI type, hypertension, diabe‑ TyG index was significantly associated
MINOCA patients tes, dyslipidemia with an increased risk of MACE (HR:
1.33, 95% CI: 1.04–1.69)
Guo, 2022, China [85] Retrospective, observational study Incidence of MACCEs during follow up Age, sex, BMI, blood pressure, smoke, TyG index was significantly associated
2030 prediabetic patients with ACS LDL-C, HDL-C, Cr, UA, eGFR, BNP, CRP, with an increased risk of MACCE (HR:
DM, hypertension 3.256, 95% CI: 2.618–4.749)
Jiao, 2022, China [86] Observational study Incidence of all cause of death and Age, gender, BMI, blood pressure, LVEF, TyG index is an independent predictor
662 ACS patients over 80 years old MACEs during follow up Gensini score, hypertension, diabetes, of long-term all-cause mortality (HR:
DM, previous MI, previous stroke, CKD, 1.64, 95% CI: 1.06–2.54) and MACE (HR:
current smoking, TC, LDL-C, HDL-C, 1.36, 95% CI: 1.05–1.95)
eGFR, UA, medication, LM lesion,
multivessel lesion and treatment
Zhao, 2021, China [87] Observational study Incidence of MACEs during follow up Age, gender, BMI, smokie, hyperten‑ TyG index is an independent predictor
1510 NSTE-ACS patients received elec‑ sion, dyslipidemia, previous history of MACE (HR: 2.433, 95% CI 1.853–3.196)
tive PCI without diabetes of MI, PCI, stroke, PAD, LM disease,
three-vessel disease, chronic total
occlusion, diffuse lesion, in-stent
restenosis, SYNTAX score, treatment of
LM, LCX, RCA, DES implantation, DCB
application, complete revasculariza‑
tion, number of stents
Page 5 of 17
Table 1 (continued)
Author, year, and country Study design and population Outcomes evaluated and Adjusted variables Key findings
evaluation methods

Ma, 2020, China [88] Observational study Incidence of MACEs during follow up Age, BMI, cblood pressure, HDL-Cl, TyG index is an independent predictor
776 ACS with T2DM patients received HbA1c, sex, smoke, drinking, pres‑ of MACE (HR:2.17, 95% CI: 1.45–3.24)
PCI ence of peripheral artery disease,
chronic kidney disease, cardiac failure,
previous myocardial infarction, past
Tao et al. Cardiovascular Diabetology

percutaneous coronary intervention,

medication, coronary artery disease
severity, presence of lesions > 20 mm
long, use of drug-coated balloon,
complete revascularization
Yang, 2022, China [89] Retrospective, observational study Incidence of MACEs during hospitali‑ Age, hypertension, DM, BMI, Hb, TyG index is an independent predictor
(2022) 21:68

549 STEMI with NOAF patients zation and follow up WBC, neutrophil, platelet, glucose, TG, of NOAF during hospitalization (OR:
TC, HDL-c, LDL-c, eGFR, Left atrium 8.884, 95% CI: 1.570–50.265)
diameter, LVEF, SS, Stent length, Killip
class ≥ II
Zhao, 2021, China [90] Observational study Incidence of MACEs during follow up Age, sex, LVEF, smoke, hypertension, The middle tertile of TyG was associated
274 STEMI patients over 18 years old hyperlipidemia, DM; Cr, heart rate, CRP with greater rates of MACEs in patients
received OCT with PR but not in those with PE (HR:
6.01; 95% CI: 1.25–28.88)
Zhang, 2021, China [91] Observational study Incidence of MACCEs during follow up Age, sex, BMI, blood pressure, medical TyG index is an independent predictor
1932 ACS patients with T2DM history, smoke, duration of diabetes of MACCES in patients with T2DM and
ACS (OR: 2.32, 95% CI: 1.92–2.80)
Zhang, 2020, China [92] Observational study Incidence of MACEs during follow up Age, gender, DM, hypertension, TyG index was positively associated
3181 ACS patients previous AMI, hemoglobin, albumin, with MACEs (HR:1.19, 95% CI: 1.01–1.41)
eGFR, TGs, LVEF, multi-vessel/ left main in patients with AMI
coronary artery
Hu, 2020, China [93] Observational study Incidence of MACEs during follow up Age, sex, smoke, hypertension, previ‑ High TyG index had a significantly
9285 ACS patients received PCI ous MI, previous stroke, previous PCI, greater risk of cardiovascular events
previous CABG, ACS status, medica‑ regardless of diabetes status (HR:1.92,
tion 95% CI: 1.33–2.77)
Zhao, 2020, China [94] Observational study Incidence of MACEs during follow up Age, sex, BMI, blood pressure, smoke, TyG index was independently associ‑
798 NSTE-ACS patients with diabetes drinking, duration of diabetes, dyslipi‑ ated with higher risk of MACEs in NSTE-
received PCI demia, prior MI, PCI, stroke, PVD, TC, ACS patients with diabetes
HDL-C, eGFR, HbA1c, LVEF, SYNTAX
score, LM treatment, DCB use, com‑
plete revascularization and number of
stents, medication
Page 6 of 17
Table 1 (continued)
Author, year, and country Study design and population Outcomes evaluated and Adjusted variables Key findings
evaluation methods
In-stent restenosis
Zhu, 2021, China [39] Retrospective study, 1574 ACS Incidence of ISR evaluated by follow- Age, sex, BMI, LVEF, hsCRP, hyper‑ TyG index was positively associ‑
patients with DES-based PCI up angiography tension, DM, previous PCI, SYNTAX ated with DES-ISR (OR: 1.424, 95% CI:
score, target vessel in LAD or RCA, 1.116–1.818)
application of intracoronary imagine;
DES-sirolimus; total length of stents,
Tao et al. Cardiovascular Diabetology

and minimal stent diameter

Arterial stiffness
Lambrinoudaki, 2018, Greece [44] Cross-sectional study, Carotid IMT, flow-mediated dilation of Mets, age, BMI, LDL-C, smoke, hyper‑ TyG index was associated with carotid
473 non-diabetic postmenopausal the brachial artery, PWV evaluated by tension atherosclerosis and AS in lean post‑
women, without overt CVD ultrasound image menopausal women (OR: 3.119, 95% CI:
(2022) 21:68

1.187–8.194)
Lee, 2018, Korea [45] Observational study, 3587 healthy AS evaluated by baPWV Age, blood pressure, BMI, LDL-C, HDL- TyG index was significantly associated
subjects C, DM, menopause with increased baPWV (OR: 2.92, 95%
CI: 1.92–4.44 in men, OR: 1.84, 95% CI:
1.15–2.96 in women)
Won, 2018, Korea [46] Cross-sectional study, AS evaluated by baPWV Age, sex, blood pressure, abdominal TyG index was independently related to
2560 subjects without CAD, stroke, obesity, HDL, smoke, DM the baPWV (β = 0.158)
and malignancies
Su, 2021, China [47] Cross-sectional study, AS evaluated by baPWV Age, sex, BMI, waist circumference, TyG index was positively associ‑
2035 subjects over 60 years old SBP, DBP, TC, HDL-C, LDL-C, UA, eGFR, ated with baPWV (OR: 1.32, 95% CI:
smoke, drinking status, CAD, hyper‑ 1.09–1.60)
tension, DM, anti-platelet agents, anti-
hypertensive agents, hypoglycemic
therapy, lipid-lowering therapy
Li, 2020, China [50] Observational study, AS evaluated by baPWV Age, sex, education, BMI, waist cir‑ TyG index was positively associ‑
4718 patients with hypertension cumference, physical activity, smoke, ated with baPWV (OR: 2.12, 95% CI:
current drinking, blood pressure, UA, 1.80–2.50)
serum homocysteine, HDL-C, LDL-C,
eGFR, DM, antihypertensive drugs,
antiplatelet drugs
Nakagomi, 2020, Japan [51] Observational study, AS evaluated by baPWV Age, BMI, blood pressure, HbA1c, FBG, TyG index was positively associated
1720 healthy men and 1098 healthy LDL-C, HDL-C, UA, smoke, alcohol with baPWV (95% CI: 0.11–0.14)
women aged between 25 and drinking
55 years
Wu, 2021, China [52] Cross-sectional study, 1895 prehyper‑ AS evaluated by baPWV Age, sex, BMI, smoke, drinking, physi‑ TyG index was positively associated
tensive patients cal activity, DM, dyslipidaemia, FBG, with baPWV (95% CI: 58.7–200.0)
TG, PBG, LDL-C, eGFR, UA, homocyst‑
eine, medications
Wang, 2021, China [53] Observational study, AS evaluated by baPWV BMI, waist circumference, blood TyG index was positively associ‑
3185 patients with T2DM pressure, LDL-C, HDL-C, WBC counts, ated with baPWV (OR: 1.40, 95% CI:
smoke, drinking, medication 1.16–1.70)
Page 7 of 17
Table 1 (continued)
Author, year, and country Study design and population Outcomes evaluated and Adjusted variables Key findings
evaluation methods

Guo, 2021, China [54] Observational study AS evaluated by baPWV, 10-year CVD age, smoke, BMI, pulse pressure, TyG index was independently associ‑
13,706 healthy subjects risk was evaluated using the Framing‑ HbA1c, TC, LDL-C, HDL-C, UA, medica‑ ated with AS (OR: 1.514, 95% CI:
ham risk score tion 1.371–1.671) and 10-year CVD risk (OR:
1.420, 95% CI: 1.147–1.756)
Yan, 2022, China [95] Cross-sectional AS evaluated by baPWV Age, sex, smoke, alcohol drinking, Higher long-term trajectory of TyG
Tao et al. Cardiovascular Diabetology

study regular exercise, BMI, blood pressure, index were independently associated
2480 individuals from Hanzhong Ado‑ hs-CRP, diabetes with increased arterial stiffness (OR:
lescent Hypertension Cohort study 2.760, 95% CI: 1.40–7.54)
Wu, 2021, China [96] Prospective study AS evaluated by baPWV Age, se, smoke, alcohol drinking, TyG index was independently
6028 individuals from Kailuan study physical activity, MAP, diabetes, hs-CRP, associated with AS (HR: 1.58, 95% CI:
and BMI at baseline 1.25–2.01)
(2022) 21:68

Coronary artery calcification

Kim, 2017, Korea [57] Observational study 4319 healthy CAC evaluated by multidetector CT Age, sex, blood pressure, BMI, LDL-C, TyG index was independently associ‑
subjects scanner HDL-C, smoke, alcohol, exercise habits ated with CAC (OR: 1.950, 95% CI:
1.23–3.11)
Won, 2020, Korea [58] Observational study 12,326 asympto‑ CAC evaluated by multidetector CT Age, male sex, BMI, blood pressure, TyG index was significantly associ‑
matic subjects scanner TC, TG, HDL-C, LDL-C, glucose, and ated with CAC progression in baseline
creatinine, smoke CACS ≤ 100
Park, 2019, Korea [97] Retrospective study 1175 individuals CAC evaluated by multidetector CT Age, sex, BMI, blood pressure, LDL-C, TyG index is an independent predictor
scanner HDL-C, exercise, alcohol, smoking, of CAC progression (OR: 1.82, 95% CI:
presence of diabetes and hyperten‑ 1.20–2.77)
sion, medication
Heart failure
Guo, 2021, China [61] Retrospective study, Cardiovascular death or rehospitaliza‑ Age, sex, BMI, blood pressure, HR, CRP, TyG index was positively associated
546 patients with CHF and T2DM tion due to HF during follow up eGFR, NT-proBNP, HbA1c, LVEF, AF, with cardiovascular death (HR: 4.42,
NYHA 95% CI: 1.49–13.15) and rehospitaliza‑
tion (HR: 1.84, 95% CI: 1.16–2.91)
Yang, 2021, China [63] Retrospective study, ECV fraction calculated by CMR meas‑ age, DM, HbA1c, NT-proBNP TyG index was the significant factor
103 hospitalized HF patients urements and T1 mapping, all-cause determined for ECV fraction (r par‑
death or HF rehospitalization during tial = 0.36) and primary outcome events
follow up (HR = 2.01, 95% CI = 1.03–4.01)

CAD coronary artery disease, T2DM type II diabetes mellitus, MACCE major adverse cardiac and cerebrovascular events, HDL-C high density lipoprotein cholesterol, UA uric acid, HR hazard ratio, CI confidence interval, CVE
cardiovascular events, BMI body mass index, hsCRP hypersensitive C-reactive protein, LVEF left ventricular ejection fraction, OR odds ratio, LDL-C low density lipoprotein cholesterol, HbA1c hemoglobin A1c, CAS coronary
artery stenosis, CACS Coronary artery calcification score, CT computed tomographic, Cr creatinine, CS coronary stenoses, CVRF cardiovascular risk factor, ACS acute coronary syndrome, MACE major adverse cardiovascular
events, MI myocardial infarction, STEMI ST-elevated myocardial infarction, OCT optical coherence tomography, PR plaque rupture, PE plaque erosion, CABG coronary artery bypass graft, OPCABG off-pump coronary
artery bypass graft, CKD chronic kidney disease, IABP intra-aortic balloon pump, eGFR estimated glomerular filtration rate, NSTE non-ST-segment elevation, GRACE Global Registry of Acute Coronary Events, MINOCA MI
patients with nonobstructive coronary arteries, Mets metabolic syndrome, DES drug-eluting stent, ISR in-stent restenosis, SYNTAX Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery,
LAD left anterior descending artery, RCA​ right coronary artery, CVD cardiovascular disease, IMT intima-mediated thickness, baPWV brachial ankle pulse wave velocity, AS arterial stiffness, FBG fasting blood glucose, PBG
postprandial blood glucose, TG triglyceride, TC total cholesterol, CAC​coronary artery calcification, TC total cholesterol, CHF chronic heart failure, HR heart rate, NT_proBNP N-terminal B-type natriuretic peptide, AF atrial
fibrillation, NYHA New York Heart Association functional classification, PCI percutaneous coronary intervention, NOAF new-onset atrial fibrillation, Hb hemoglobin, WBC white blood cell, PVD Peripheral vascular disease,
MAP mean arterial blood pressure
Page 8 of 17
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 9 of 17

stenosis were also associated with a higher TyG index STEMI patients who underwent PCI and found that the
[26]. Nevertheless, the current guidelines for the primary TyG index was positively associated with an increased
prevention of CVD indicate that asymptomatic individu- risk of MACCEs in STEMI patients within 1 year fol-
als without cardiovascular risk factors (CVRFs) are not lowing PCI after adjusting for confounding factors (HR:
considered candidates for preventive treatments [27]. 1.529, 95% CI 1.001–2.061) [33]. Additionally, Mao et al.
Recently, a study by the Progression of Early Subclinical evaluated 438 patients with NSTE-ACS and followed
Atherosclerosis (PESA) indicated that in middle-aged them for 12 months after admission to assess the risk of
populations without CVRF, the prevalence of subclini- MACEs. The results indicated that the TyG index pre-
cal atherosclerosis is approximately 50% [28]; therefore, sented strong diagnostic power for CVRFs, including glu-
identifying patients in this population who are at early cose metabolism disorder and metabolic syndrome [34].
risk for subclinical atherosclerosis is of great impor- Furthermore, the TyG index was found to be an inde-
tance. In a retrospective observational study, Park et al. pendent predictor of a high SYNTAX score (OR: 6.055,
included 1250 asymptomatic Korean individuals without 95% CI 2.915–12.579) and the occurrence of MACEs
traditional CVRFs to evaluate coronary stenosis by coro- (HR: 1.878, 95% CI 1.130–3.121). These two studies sup-
nary CT angiography. They found that the TyG index was ported the potential value of using the TyG index for
associated with an increased risk of CAD (OR: 1.473, 95% predicting clinical outcomes in patients with different
CI 1.026–2.166), especially in patients with noncalcified groups of ACS. However, these previous studies were
and mixed plaques [29]. These studies support the notion carried out only with patients who had an established
that the TyG index is an independent marker that can be DM diagnosis or impaired glucose tolerance. Is the TyG
used to predict subclinical CAD both in general popula- index also useful for predicting the prognosis of patients
tions and individuals with established risk factors. without glucose metabolic disorders? As discussed
above, the TyG index has been reported to be useful for
Acute coronary syndrome (ACS) the early identification of apparently healthy individu-
ACS is the most severe type of ischaemic heart disease als at high risk of developing CVD. Therefore, whether
and describes a range of myocardial ischaemic condi- the TyG index can predict the clinical outcome of ACS
tions, including unstable angina (UA), non-ST elevated patients without established risk factors may be of clini-
myocardial infarction (NSTEMI), and ST-elevated myo- cal interest. In an analysis of 1655 ACS patients without
cardial infarction (STEMI) [30]. Despite the use of cur- diabetes and low-density lipoprotein cholesterol (LDL-C)
rent guideline-recommended therapeutics, including levels less than 1.8 mmol/L, Zhang et al. found that a high
coronary artery revascularization techniques such as per- TyG index level was associated with a higher incidence
cutaneous coronary intervention (PCI) or coronary artery of AMI (21.2% vs. 15.2%), larger infarct size and higher
bypass grafting (CABG) and optimal drug treatments, incidence of revascularization (8.9% vs. 5.0%) compared
some patients with ACS remain at high risk for recur- with ACS patients with LDL-C levels below 1.8 mmol/L.
rent cardiovascular events (CVEs) [31]. Thus, it is critical Interestingly, patients with a high TyG index were prone
to identify ACS patients who are at a high risk of CVEs to develop DM during follow-up, indicating that they
so that intense strategies can be provided. Studies have might be more likely to develop multivessel CAD, which
suggested that the TyG index might be a useful marker would be a potential contributor to the increased inci-
for risk stratification and for predicting the prognosis of dence of revascularization [35]. The results of this study
ACS patients with or without diabetes. A retrospective suggested that a high TyG index level might be a valid
cohort study enrolled a total of 2531 consecutive patients predictor for early stratification in ACS patients with rel-
with established diabetes. These patients received coro- atively low risk.
nary angiography (CAG) due to ACS and completed In addition to obstructive ACS, an elevated TyG index
3 years of clinical follow-up. The authors found that the is also independently associated with a poor progno-
incidence of MACEs increased along with the TyG index sis in MI patients with nonobstructive coronary arteries
tertiles and that the TyG index was an independent pre- (MINOCA). MINOCA is a distinct clinical entity and
dictor of MACEs (HR: 1.455, 95% CI 1.208–1.753) after presents a heterogenous diagnosis of multiple causes,
adjusting for traditional CVRFs, irrespective of whether including plaque rupture or erosion, coronary spasm,
non-invasive or invasive treatments were administered thromboembolism, spontaneous dissection, microvascu-
[32]. However, in this study, subgroup analysis showed lar dysfunction and supply/demand mismatch, account-
that the prognostic value of the TyG index was only sig- ing for 5–10% of all MI cases. Gao et al. recruited a total
nificant in patients with UAP (adjusted HR: 1.604, 95% CI of 1179 MINOCA patients who completed a median fol-
1.270–2.027). One explanation for this result may be the low-up of 41.7 months and found that the patients in the
small sample size. Subsequently, Luo et al. included 1092 higher TyG index tertiles had an increased risk of MACEs
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 10 of 17

(HR: 1.33, 95% CI 1.04–1.69) after adjusting for multi- mounting evidence has revealed that elevated baPWV
variate risk factors. Of note, the TyG index remained a is associated with an increased risk of hypertension
robust risk factor in overall MINOCA patients or sub- [48] and diabetes [49], which are major risk factors for
groups, including DM or non-DM patients and those AS. Thus, it is of great importance to focus on the link
with LDL-C levels higher or lower than 1.8 mmol/l, sug- between the TyG index and AS in different populations.
gesting that the TyG was a reliable marker for predicting Li et al. performed a study involving a large number of
outcomes independent of glucose-lipid metabolic status hypertensive adults and revealed that there was a sig-
in patients with MINOCA [36]. nificant positive association between the TyG index and
baPWV (OR: 1.02, 95% CI 0.83–1.20), especially in men
In‑stent restenosis [50]. In contrast, Nakagomi et al. found that the asso-
PCI is currently the most common revascularization ciation between the TyG index and increased levels of
strategy in Chinese patients with CAD, even those with baPWV was stronger in women [51]. This discrepancy
diabetes. However, despite considerable improvements might be due to differences in the age distribution
in outcomes due to the widespread use of drug-eluting between these two studies; the mean age of individuals
stents, in-stent restenosis (ISR) remains one of the major in Nakagomi et al. was 38.8 years old, while it was 64.41
challenges after PCI, occurring in 3–20% of patients [37, in the study by Li et al. Therefore, further studies are
38]. Therefore, the early identification of patients with a needed to examine the relationship among IR, AS, sex
high risk of ISR may have great clinical importance. Zhu and age. Recently, Wu et al. added more data to support
et al. retrospectively recruited 1574 patients who were the association of the TyG index with the progression
admitted for ACS and underwent successful drug-eluting of AS in hypertensive individuals. In their study, 1895
stent (DES)-based PCI. They found that an elevated TyG prehypertensive and hypertensive patients were fol-
index was independently and positively associated with lowed up for a median of 4.71 years, and their results
the occurrence of DES-ISR [39]. However, the incremen- indicated that there was a linear and positive associa-
tal predictive value of the TyG index for DES-ISR was tion between the TyG index and three baPWV param-
slight; thus, multicentre, large-scale clinical studies are eters (baPWV change, baPWV change rate and baPWV
necessary to clarify the relationship between the TyG slope) in hypertensive populations rather than in prehy-
index and ISR. pertensive populations [52]. These results suggest that
the interaction between IR and hypertensive status may
Arterial stiffness contribute to AS development and progression; there-
Atrial stiffness (AS) is one of the earliest types of func- fore, more attention should be given to IR indexes in
tional damage that occurs during the vascular ageing patients with hypertension. In addition to hypertension,
process, during which the arterial elasticity decreases patients with diabetes can also develop AS. In a study
and pulse pressure increases [40, 41]. Mounting evi- involving 3185 patients with T2DM, Wang et al. showed
dence has suggested that AS is a powerful predictor a positive and dose–response relationship between the
for the future risk of CVDs such as ACS, heart failure TyG index and AS, assessed by baPWV after adjusting
(HF), and ischaemic or haemorrhagic stroke [42, 43]. for confounding factors (OR: 1.40, 95% CI 1.16–1.70).
Considering that patients with AS suffer from long- Moreover, compared to the HOMA-IR index, the TyG
term pathological progression, there is an urgent need index was better at predicting an increased incidence of
for reliable biomarkers to identify patients in the early AS in T2DM patients [53], providing evidence to sup-
stage and to develop preventive therapeutics. In an port that the TyG index can serve as a simple but reli-
analysis of 473 postmenopausal women without diabe- able biomarker to evaluate AS in diabetic patients.
tes, Lambrinoudaki et al. showed a positive association Additionally, Guo et al. further demonstrated a positive
between the TyG index and AS by measuring brachial association between the TyG index and 10-year CVD
ankle pulse wave velocity (baPWV). Nonetheless, this risk among a large number of patients with AS in China
study was limited by its small size, and it included only [54]. The results of all these studies reflect the potential
postmenopausal women [44]. Subsequently, a Korean value of the TyG index in predicting AS and in provid-
study enrolling 3587 healthy adults found that com- ing guidance to clinicians regarding appropriate treat-
pared to the HOMA-IR index, the TyG index was inde- ment strategies.
pendently associated with increased baPWV [45]. Won
et al. [46] and Su et al. [47] provided further evidence to Coronary artery calcification
support the predictive value of the TyG index in iden- Coronary artery calcification (CAC), defined as an
tifying AS among healthy Korean adults and Chinese Agatston score > 0 by a multidetector CT scanner, is a
community-dwelling elderly individuals. Furthermore, sensitive marker for detecting the existence of early
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 11 of 17

atherosclerosis. Additionally, CAC plays an important Potential explanations of the TyG index as a marker
role in predicting adverse CVEs [55, 56]. Therefore, the for predicting cardiovascular disease
identification of patients who have a high risk of CAC The exact mechanism underlying the relationship
may have significant clinical relevance. A Korean study between the TyG index and CVD remains unknown. It
performed in 2016 was the first to explore the relation- is very clear that TyG is an index consisting of two risk
ship between the TyG index and CAC in 4319 appar- factors for CVD, lipid-related and glucose-related fac-
ently healthy adults. The data showed that the TyG tors, which are reflective of IR in the human body. Recent
index was independently associated with the presence of studies have identified the TyG index as a reliable marker
CAC after adjusting for multiple risk factors (OR: 1.95, of IR, which may be one of the explanations for this asso-
95% CI: 1.23–3.11) [57]. In addition, Won et al. [58] ciation [15]. IR is a risk factor for CVD, which not only
enrolled a large number of asymptomatic healthy adults leads to the development of CVD in both the general
without severe CAC at baseline and demonstrated that population and patients with diabetes but also predicts
a high TyG index was significantly associated with CAC the cardiovascular prognosis of patients with CVD [7].
progression, which was defined as a difference ≥ 2.5 The potential mechanisms underlying IR and CVD are
between the square roots of the baseline and follow- described as follows (Fig. 3).
up CAC scores (Δ√ transformed CACS) [58]. Notably, First, IR can induce glucose metabolism imbalance,
these two studies on the relationship between the TyG contributing to hyperglycaemia, which in turn triggers
index and CAC were based on Korean healthy popula- inflammation and oxidative stress. Additionally, systemic
tions, which does not represent the characteristics of lipid disturbances have also been reported, including
all patients with CAC. Thus, the significance of the TyG elevated TG, small dense LDL, and postprandial lipae-
index for predicting CAC progression in individuals mia levels and reduced high-density lipoprotein (HDL)
who have CAD still needs to be clarified. levels, which may cause the initiation of atherosclerosis
[64]. Moreover, in established ischaemic myocardium,
Heart failure reduced insulin activity limits glucose bioavailability and
Epidemiological studies have demonstrated that heart causes a shift to fatty acid metabolism, ultimately lead-
failure (HF) is a growing health burden, with a preva- ing to increased myocardial oxygen consumption and a
lence of up to 1–2% in adult populations [59]. Recent reduction in the compensatory capacity of non-infarcted
studies have indicated that IR was the main cause for myocardium [65]. These pathological metabolic disorders
the poor prognosis of patients with HF [60]. Thus, the further aggravate CAD progression.
identification of IR surrogate markers would play a vital Second, studies have shown that IR can induce an
role in the prevention and treatment of HF. Guo et al. increased production of glycosylated products and free
showed that the TyG index was positively related to the radicals, leading to nitric oxide (NO) inactivation. The
prognosis of patients with chronic HF and DM. They abnormal secretion of NO related to IR damages the
revealed that the higher the TyG index is, the higher the vascular endothelium and causes endothelium-depend-
risk of cardiovascular death or rehospitalization caused ent vasodilation [66]. Furthermore, IR also activates the
by HF [61]. In addition to predicting the prognosis of mitochondrial electron-transport chain and induces
patients with HF, the TyG index was also identified as overproduction of reactive oxidative stress (ROS), which
a novel biomarker of cardiac fibrosis in these patients. is another cause of impaired endothelial function [67].
The myocardial fibrosis estimated by cardiovascu- The abnormal endothelial function observed in patients
lar magnetic resonance (CMR) can provide important with diabetes extends to the coronary microcirculation
prognostic information on the cardiovascular risk of HF and myocardial energy metabolism. In patients with car-
[62]. Yang et al. analysed 103 hospitalized HF patients diac ischaemia, IR is inversely associated with median
and found that myocardial fibrosis could quantified by colony forming unit endothelial cells, contributing to
the extracellular volume (ECV) fraction using CMR. a reduced density of collaterals in response to cardiac
Multivariate regression linear analysis showed that the ischaemia [68].
TyG index was a significant determinator for the ECV Moreover, many experimental studies have clearly
fraction (rpartial = 0.36) in patients with HF. Addition- established that the insulin receptor can mediate related
ally, during a median follow-up of 12.3 months, the TyG signalling to sensitize platelets to the antiaggregating
index was identified as an independent risk factor for actions of prostaglandin I2 (PGI2) and NO. On the one
all-cause mortality and HF hospitalization (HR: 2.01, hand, IR may contribute to platelet hyperactivity. On the
95% CI 1.03–4.01), supporting the utility of the TyG other hand, it can increase adhesion-induced and throm-
index in stratification metrics during the management boxane A2 (TxA2)-dependent tissue factor expression
of HF [63]. in platelets. These events have been implicated in both
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 12 of 17

Fig. 3 Potential molecular mechanisms that contribute to the predictive role of the triglyceride-glucose (TyG) index in cardiovascular diseases
(CVD). Insulin resistance (IR) is a hallmark of metabolic syndrome and has been evidenced as a risk factor for CVD. The TyG index has been identified
as a reliable alternative marker of IR, which may explain the association between the TyG index and CVD. The molecular mechanisms underlying IR
and CVD include metabolic flexibility, endothelial dysfunction, coagulation disorders and smooth muscle cell dysfunction. TyG: triglyceride-glucose;
CVD: cardiovascular diseases; IR: insulin resistance; NO: nitric oxide; ROS: reactive oxidative stress; TxA2: thromboxane A2; TF: tissue factor; PGI2:
prostaglandin I2

thrombosis and inflammation [69], which may partly Limitations of the TyG index as a marker
explain the obstructive ACS or nonobstructive coronary in cardiovascular diseases
thromboembolism observed in some patients. The TyG index is a composite indicator composed of fast-
In addition, previous studies have demonstrated that ing TG and FG, which could be used as an alternative test
IR, which is usually accompanied by hyperglycaemia, for recognizing IR in large-scale studies or for evaluating
induces excessive glycosylation, which can promote populations at high risk of developing diabetes. Notably,
smooth muscle cell proliferation, collagen crosslinking, several studies have suggested that the TyG index was
and collagen deposition. These pathological events then better than the HOMA-IR index in predicting the devel-
contribute to increased diastolic left ventricular stiffness, opment of atherosclerosis and poor outcomes such as the
cardiac fibrosis and, ultimately, heart failure [7]. increased occurrence of carotid atherosclerosis [74] and
Finally, in addition to its role in hyperglycaemia, IR CAC progression as evaluated by the CAC score [75].
plays an important role in hyperlipidaemia. Studies have Moreover, according to previous studies, the direct quali-
suggested that increased TG levels can induce elevated fication of serum insulin levels is expensive and is not
free fatty acid (FFA) levels and promote the increased available in most cities in developing counties; an alter-
flux of FFAs from adipose tissue to non-adipose tissue, native test derived from fasting TG and FBG is less costly
which may accompany IR [70]. More importantly, the and universally available. In addition, due to the need
retention of cholesterol-rich and TG-rich ApoB-contain- for quantitation, exogenous insulin may interfere with
ing remnants within the coronary wall may be considered the value of the HOMA-IR index. Therefore, the cur-
related to the pathogenesis of atherosclerosis [71]. Thus, rent evaluation of IR by the HOMA-IR index may not be
lowering TG levels appears to be an additional target applicable to diabetic patients who are treated with insu-
in patients with a high CVD risk. Additionally, activa- lin. Since the TyG index is a formula composed of fasting
tion of the renin-angiotensin system [72] and impaired TG and FG, it does require the quantification of insulin
cardiac calcium processing capacity [73] may also be and thus may be widely applicable in all diabetic patients
contributors. treated with insulin. In summary, TyG is regarded as an
accessible and reliable index for IR in individuals with a
high risk of CVD, especially in developing counties.
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 13 of 17

However, there are still several observations that of average TyG index for each pair of consecutive evalu-
have failed to support the association between the TyG ations multiplied by the time between these two con-
index and CVEs. First, the rationale for the first use of secutive visits in years), showing a multivariate-adjusted
the TyG index in 2008 was that IR is a common cause HR of 1.39 (95% CI 1.21–1.61) [77]. These authors found
of the increase in TG and glucose levels in healthy indi- that the cumulative effect of the TyG index seemed to be
viduals [9]. Therefore, the application of the TyG index independent and better than the TyG index at baseline in
in CVD patients can be affected by hyperlipidaemia and predicting CVD. Therefore, the use of the TyG index at
diabetes. To justify the value of the TyG index as a bio- baseline as a biomarker to predict outcomes of CVD may
marker, hypertriglyceridaemia and glucose metabolic be less robust. Evaluating the mean changes in the TyG
disorder should be well controlled. Nevertheless, sev- index in CVD progression and follow-up is warranted in
eral patients with extremely high TGs or FBSs were still future studies.
enrolled in previous clinical studies, which could not Moreover, most studies regarding the use of TyG in
explore reverse causality in the application of the TyG CVD have been performed in middle-aged or elderly
index in these CVD patients. For example, Laura et al. individuals, and no data are currently available concern-
did not find an association between the TyG index and ing the value of TyG in young subjects. Dikaiakou et al.
CVD in subjects with T2DM or hypertension at baseline. found that the TyG index showed a positive correla-
Their outcomes could be explained by the hypothesis that tion with IR among both children and adolescents [78];
patients previously diagnosed with diabetes or hyper- however, data regarding the predictive ability of the
tension were under treatment or had adopted healthier TyG index in identifying the presence of future CVD in
habits, so their analytical parameters might be well con- these younger individuals are limited. In addition to the
trolled [20]. Cho et al. also failed to find an independent lack of information on different age groups, differences
association between the TyG index and the presence of in the TyG index between the sexes are also still uncer-
CAD or obstructive CAD in 996 patients with estab- tain. Compared to women, men have more risk fac-
lished diabetes after adjusting for traditional CVRFs [76]. tors for metabolic diseases. For example, men are more
Unfortunately, in this study, detailed information regard- likely to smoke and drink and have higher serum uric
ing the doses used, classes of patients enrolled and even- acid and serum homocysteine levels and a lower esti-
tual changes in related drugs was unavailable. Hence, the mated glomerular filtration rate (eGFR) [51]. Therefore,
potential influence of medications taken for hyperlipi- further sex-related studies are warranted to explore the
daemia, diabetes and hypertension could not be excluded relationship between the TyG index and CVD. Finally,
in these studies. Finally, other important information, dietary habits can dramatically affect TG levels. However,
including physical activity, alcohol consumption, and nutrition data are missing from most studies, so we were
family history of diseases, was also lacking in many clini- unable to adjust for dietary habits when evaluating the
cal studies. diagnostic or predictive value of the TyG index in CVD.
Second, medical doctors involved in clinical work
usually first pay attention to FBG and TG levels when Conclusions
screening patients with a high risk of CVD. However, the Overall, IR, a well-established hallmark of metabolic
question of how the TyG index can add to the predictive disorders and systemic inflammation, is not only a sub-
value of TG and FBG levels remains. The comparison stantial risk factor for CVD but also contributes to a
of the predictive values between the TyG index and TG worse prognosis. Current studies have confirmed that
and FBG (and may be the combination) is also missing in the TyG index can be used as a reliable and conveni-
some studies. In addition, CVD is a series of dynamic and ent surrogate for IR, which may be optimized for risk
progressive disturbances, and the development of acute stratification as well as outcome prediction for CVD.
diseases such as MI may lead to stress hyperglycaemia, Nevertheless, based on current studies, there are some
which may affect the diagnostic or predictive value of the knowledge gaps that need to be addressed. First, some
TyG index based on the TyG formula. In most studies, investigators have proposed that it would be interest-
TG and FBG were examined only at baseline, regardless ing to explore whether a postprandial TyG index might
of their changes over time, which may lead to potential have clinical significance. Because increased postpran-
regression dilution bias. Therefore, the measurement of dial levels of TG and glucose are metabolically abnor-
the TyG index at baseline alone does not reflect the lon- mal responses to IR, an elevated postprandial TyG
gitudinal association between the TyG index and CVD index may be associated with a higher risk of diabetes
risk over time. Recently, Cui et al. showed that the risk or CVEs, which remains to be clarified. Second, regard-
of CVD development increased along with the quartile ing the predictive power of the TyG index in CVD,
of the cumulative TyG index (defined as the summation
Tao et al. Cardiovascular Diabetology (2022) 21:68 Page 14 of 17

especially in CAD, accumulating studies have shown 4. Zhao D, Liu J, Wang M, Zhang X, Zhou M. Epidemiology of cardiovascu‑
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when introducing the TyG index into an established Howard BV, Devereux RB. Myocardial mechano-energetic efficiency and
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Not applicable. tions. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub.
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Author contributions 11. Guerrero-Romero F, Simental-Mendía LE, González-Ortiz M, Martínez-
FH and JJL designed the work; LCT and JNX wrote the first draft of manu‑ Abundis E, Ramos-Zavala MG, Hernández-González SO, Jacques-Cama‑
script; TtW provided critical analysis. All authors read and approved the final rena O, Rodríguez-Morán M. The product of triglycerides and glucose, a
manuscript. simple measure of insulin sensitivity. Comparison with the euglycemic-
hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95(7):3347–51.
Funding 12. Vasques AC, Novaes FS, de Oliveira MS, Souza JR, Yamanaka A, Pareja JC,
This research was funded by the National Natural Science Foundation of Tambascia MA, Saad MJ, Geloneze B. TyG index performs better than
China (NSFC) Grants 82170356, China Postdoctoral Science Foundation HOMA in a Brazilian population: a hyperglycemic clamp validated study.
grant 2018M642317, Post-Doctoral Foundation of Jiangsu Province Grant Diabetes Res Clin Pract. 2011;93(3):e98–100.
2018K095B, Six Talent Peaks Project of Jiangsu Province grants WSN-202 and 13. Lee SH, Kwon HS, Park YM, Ha HS, Jeong SH, Yang HK, Lee JH, Yim HW,
WSW-183, Changzhou Sci&Tech Program Grant CJ20210091, Maternal and Kang MI, Lee WC, et al. Predicting the development of diabetes using
Child Health Research Project of Jiangsu Province Grant F201803. the product of triglycerides and glucose: the Chungju Metabolic Disease
Cohort (CMC) study. PLoS ONE. 2014;9(2): e90430.
Availability of data and materials 14. Navarro-González D, Sánchez-Íñigo L, Pastrana-Delgado J, Fernández-
Not applicable. Montero A, Martinez JA. Triglyceride-glucose index (TyG index) in
comparison with fasting plasma glucose improved diabetes prediction in
patients with normal fasting glucose: the Vascular-Metabolic CUN cohort.
Declarations Prev Med. 2016;86:99–105.
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