Development and validation of age- and gender-specific reference intervals for the triglyceride-glucose index in a large Chinese healthy adult population

Background: The triglyceride-glucose (TyG) index is a recognized surrogate marker of insulin resistance. However, validated reference intervals (RIs) for the TyG index in large, general healthy populations are currently lacking, limiting its standardized application in clinical practice. Methods: This retrospective study established and validated TyG index RIs using data from adults (≥18 years) undergoing routine health examinations. The derivation cohort included individuals without known diabetes, dyslipidemia, or obesity. The TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. After outlier exclusion, we analyzed the age-TyG relationship using restricted cubic splines and threshold analysis to determine optimal age stratification. Gender- and age-specific RIs were defined as the 2.5th-97.5th percentiles. An independent cohort of 127,143 healthy individuals was used for validation, with success defined as <10% of values falling outside the proposed RIs. Results: A total of 201,623 individuals were initially screened for the derivation cohort. Analysis revealed a significant nonlinear relationship between TyG and age, with an inflection point at 64.21 years, justifying stratification into 18-64 and ≥64-year groups. The overall RI was 7.47-8.90. Stratified RIs were: 7.47-8.91 for males aged 18-64, 7.46-8.90 for females aged 18-64, 7.44-8.90 for males aged ≥64, and 7.50-8.90 for females aged ≥64. In the independent validation cohort, only 4.76% to 5.37% of values fell outside the corresponding RIs, confirming their robustness. Conclusion: This study establishes and validates age- and gender-stratified reference intervals for the TyG index in a large Chinese healthy population. These intervals, benchmarked against a critical age threshold of 64 years, provide a reliable standard for clinical interpretation and enhance the utility of the TyG index in metabolic risk assessment.