Beyond Insulin Resistance: Why Diabetes Status Dictates the Cardiovascular Risk of the Triglyceride-Glucose Index

Highlights

The TyG Index as a Marker

The Triglyceride-Glucose (TyG) index, a reliable surrogate for insulin resistance, shows a complex, non-linear relationship with subclinical myocardial injury (SCMI) in the general population.

Diabetes as a Critical Modifier

The association between TyG and myocardial injury is not universal; it is significantly modified by the presence of diabetes, which transforms the risk trajectory from L-shaped to J-shaped.

Clinical Stratification

Clinicians should interpret TyG levels differently based on a patient’s glycemic status to improve the accuracy of cardiovascular risk stratification and early detection of myocardial damage.

Background: The Challenge of Subclinical Myocardial Injury

Subclinical myocardial injury (SCMI), often identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT) in the absence of overt symptoms, is a potent predictor of heart failure, atrial fibrillation, and cardiovascular mortality. Identifying modifiable risk factors for SCMI is essential for primary prevention. While insulin resistance is a known driver of metabolic and cardiac dysfunction, its direct assessment via the hyperinsulinemic-euglycemic clamp is clinically impractical.

The Triglyceride-Glucose (TyG) index has emerged as a cost-effective, easily accessible alternative indicator of insulin resistance. While previous studies have linked high TyG levels to coronary artery calcification and arterial stiffness, its prospective association with chronic, low-grade myocardial damage—and how this relationship might be altered by a diagnosis of diabetes—remained largely unexplored until now.

Study Design and Methodology

To address this gap, researchers analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, a large-scale prospective cohort. The investigation was divided into two phases:

The cross-sectional study included 11,478 participants (mean age 56.78 years) to assess the baseline correlation between the TyG index and hs-cTnT levels. The prospective cohort study followed 8,801 participants (mean age 56.57 years) over a six-year period to observe the incidence of new-onset SCMI, defined as an hs-cTnT level of 14 ng/L or higher.

The TyG index was calculated using the standardized formula: ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL) / 2]. Researchers adjusted for a wide range of confounders, including age, sex, race, body mass index (BMI), blood pressure, smoking status, and medication use, to ensure the robustness of the findings.

Key Findings: The U-Shaped Paradox and Diabetes Modification

The study yielded several groundbreaking insights into the metabolic-cardiac axis:

1. Baseline Associations

In the cross-sectional analysis, a positive linear association was observed between the TyG index and baseline hs-cTnT levels (r = 0.13, p < 0.001). However, when stratified by diabetes status, this association remained significant only in diabetic participants (adjusted Odds Ratio [aOR] = 1.64, p = 0.020). In non-diabetic participants, the association was not statistically significant (aOR = 0.89, p = 0.374).

2. Longitudinal Risk and the U-Shaped Curve

Over the six-year follow-up, the overall population exhibited a U-shaped association between the TyG index and the incidence of hs-cTnT elevation. This suggests that both very low and very high TyG levels may be associated with increased risk, though the underlying drivers likely differ.

3. The Shift: L-Shaped vs. J-Shaped

The most striking finding was the divergence based on diabetes status. In participants without diabetes, the relationship was L-shaped (aOR = 0.72, p = 0.006), suggesting that higher TyG levels within a certain range did not necessarily escalate injury risk. Conversely, in participants with diabetes, the relationship was J-shaped (aOR = 2.09, p < 0.001), indicating a sharp increase in the risk of myocardial injury as the TyG index rose.

Expert Commentary: Mechanistic Insights and Clinical Utility

The modification of the TyG-SCMI association by diabetes highlights a critical biological intersection. In diabetic patients, a high TyG index likely reflects a state of severe insulin resistance coupled with glucotoxicity and lipotoxicity. These metabolic stressors promote oxidative stress, systemic inflammation, and mitochondrial dysfunction within cardiomyocytes, leading to the chronic leakage of troponin T.

The observed L-shaped association in non-diabetic individuals is more complex. It suggests that in the absence of chronic hyperglycemia, the heart may possess different compensatory mechanisms for handling lipid fluctuations. However, the J-shaped curve in the diabetic group underscores that once the glucose metabolism is disordered, the synergistic effect of hypertriglyceridemia and hyperglycemia becomes significantly more toxic to the myocardium.

From a clinical perspective, these findings suggest that the TyG index is not a “one-size-fits-all” biomarker. For patients with diabetes, monitoring and lowering the TyG index through lifestyle interventions or pharmacotherapy (such as statins, fibrates, or SGLT2 inhibitors) may be particularly beneficial for preserving myocardial integrity.

Limitations and Future Directions

While the study benefits from the rigorous ARIC data and prospective design, certain limitations exist. The TyG index was measured at a single time point, which may not reflect long-term metabolic fluctuations. Additionally, while hs-cTnT is a sensitive marker of injury, it does not specify the exact etiology of the damage (e.g., ischemic vs. non-ischemic). Future research should investigate whether aggressive lowering of the TyG index in diabetic populations directly translates to a reduction in clinical heart failure events.

Conclusion

This study provides the first evidence of a U-shaped association between the TyG index and subclinical myocardial injury, while identifying diabetes as a definitive modifier of this risk. By recognizing that the cardiovascular implications of the TyG index shift from L-shaped to J-shaped in the presence of diabetes, clinicians can better stratify patients and tailor metabolic management to protect the heart before overt disease manifests.

References

Abudukeremu A, Lv J, Liu W, et al. Diabetes modifies the association between the triglyceride-glucose index and subclinical myocardial injury: A prospective cohort study. Cardiovasc Diabetol. 2025;24(1):443. doi:10.1186/s12933-025-02979-z.