What is the association between the Triglyceride and Glucose Index (TyG) and Non-Alcoholic Fatty Liver Disease (NAFLD)?

The Triglyceride and Glucose Index (TyG) as a Strong Predictor of NAFLD

The Triglyceride and Glucose Index (TyG) is a reliable and significant predictor of nonalcoholic fatty liver disease (NAFLD), with higher TyG values strongly associated with both the development and presence of NAFLD. Multiple studies demonstrate that TyG serves as an effective surrogate marker for insulin resistance, which is a key pathogenic factor in NAFLD development.

What is the TyG Index?

The TyG index is calculated using the formula:

• TyG = Ln [Triglycerides (mg/dL) × Fasting Plasma Glucose (mg/dL)/2]

This simple calculation combines two key metabolic parameters that are routinely measured in clinical practice:

• Serum triglyceride levels
• Fasting plasma glucose levels

Evidence Supporting TyG-NAFLD Association

Predictive Value for Incident NAFLD

• A large cohort study of 16,093 Japanese individuals demonstrated that higher TyG index values significantly predicted the development of new NAFLD cases 1
• Individuals in the highest TyG tertile had 1.67 times higher risk (men) and 2.06 times higher risk (women) of developing NAFLD compared to those in the lowest tertile 1
• Another study with 52,575 participants showed that over a median 5.1-year follow-up, the TyG index was significantly associated with NAFLD development with a hazard ratio of 1.246 2

Diagnostic Performance

• The TyG index has been shown to be superior to the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in predicting NAFLD in Korean adults 3
• A TyG index threshold of 8.24 appears to be the level at which NAFLD risk significantly increases 2

TyG-Related Parameters

Recent research has explored enhanced versions of the TyG index that incorporate obesity markers:

1. TyG-BMI (TyG × BMI)

   • Particularly effective for predicting liver fibrosis in NAFLD patients
   • A TyG-BMI value of 259 provides optimal sensitivity (78.3%) and specificity (51.3%) for predicting liver fibrosis 4
   • Recent evidence shows TyG-BMI is independently associated with both NAFLD and significant liver fibrosis, with superior predictive ability compared to the TyG index alone 5

2. TyG-WC (TyG × Waist Circumference)

   • Better indicator for NAFLD detection than TyG alone
   • A TyG-WC value of 876 provides optimal sensitivity (81.3%) and specificity (52.3%) for predicting NAFLD 4

Pathophysiological Basis for the Association

The strong association between TyG and NAFLD is explained by the underlying metabolic abnormalities in NAFLD:

1. Dyslipidemia in NAFLD:

   • NAFLD is characterized by proatherogenic dyslipidemia with high triglycerides, increased VLDL, higher concentration of small dense LDL, and low HDL 6
   • In NAFLD, there is increased secretion of triglycerides in the form of VLDL and delayed triglyceride clearance 6

2. Glucose Metabolism:

   • NAFLD has a bidirectional association with Type 2 diabetes 6
   • Around one-third to two-thirds of diabetic patients have NAFLD 6

3. Insulin Resistance:

   • TyG serves as a surrogate marker for insulin resistance, which is a central pathogenic factor in NAFLD
   • De novo lipogenesis (synthesis of fatty acids) is 5-fold greater in NAFLD compared to normal individuals 6

Clinical Applications

The TyG index offers several advantages for clinical use:

• Simplicity: Requires only triglyceride and fasting glucose measurements, which are routinely available
• Cost-effectiveness: Uses standard laboratory tests without need for specialized equipment
• Non-invasive: Avoids the need for liver biopsy
• Early detection: Helps identify individuals at risk for NAFLD before clinical manifestation
• Risk stratification: Higher TyG values correlate with increased NAFLD risk

Important Caveats

• While TyG is a valuable tool for NAFLD risk assessment, diagnosis still requires imaging confirmation (ultrasonography, CT, or MRI)

• The TyG index should be interpreted alongside other clinical factors including:

  • Obesity (BMI and waist circumference)
  • Presence of metabolic syndrome components
  • Alcohol consumption history (to rule out alcoholic fatty liver disease)
  • Other causes of liver disease

• Sex-specific differences exist in TyG thresholds, with women typically having lower cutoff values than men 1

In conclusion, the TyG index represents a valuable clinical tool for identifying individuals at risk for NAFLD, with strong evidence supporting its use as a predictor of both incident NAFLD and the presence of existing disease. The enhanced versions (TyG-BMI and TyG-WC) offer additional predictive value, particularly for assessing liver fibrosis risk.