An Increasing Triglyceride-Glucose Index Is Associated with a Pro-Inflammatory and Pro-Oxidant Phenotype

Area of Science:

• Biochemistry
• Endocrinology
• Cardiovascular Medicine

Background:

• Insulin resistance is a key factor in metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD).
• The triglyceride-glucose (TyG) index is a validated measure of insulin resistance and a predictor of MetS, T2DM, albuminuria, and ASCVD.
• Mechanistic insights into these associations are limited.

Purpose of the Study:

• To investigate the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acid (FFA) levels, and adipokine dysregulation.
• To explore these associations in a cohort of controls and patients with nascent MetS.

Main Methods:

• A cohort of 102 participants (59 MetS, 43 controls) was studied, excluding individuals with diabetes, ASCVD, smoking, or macro-inflammation.
• Fasting blood samples were collected for plasma analysis and monocyte isolation.
• Receiver Operating Characteristic (ROC) curve analysis was used to assess the predictive value of the TyG index for MetS.

Main Results:

• The TyG index demonstrated excellent prediction of MetS (Area Under Curve = 0.87) and correlated with hepatic and adipose tissue insulin resistance.
• Serum RBP-4 and non-HDL cholesterol levels increased significantly across TyG index tertiles.
• Increased TyG index was significantly associated with elevated markers of inflammation (CRP, IL-6, chemerin, endotoxin), oxidative stress (oxidized LDL, nitrotyrosine), and monocyte TLR-4/TLR-2 signaling.

Conclusions:

• The TyG index is a strong predictor of MetS and associated cardiometabolic risks.
• A pro-inflammatory and pro-oxidant state, along with elevated non-HDL cholesterol, may mechanistically link higher TyG index to increased risk of T2DM and ASCVD.