TyG-Centered Endocrine-Metabolic Architecture in Patients with Thyroid Dysfunction: A Systems Phenotyping Study

Area of Science:

• Endocrinology
• Metabolic Health
• Systems Biology

Background:

• Metabolic dysfunction involves complex interactions including insulin resistance, dyslipidemia, and inflammation.
• The triglyceride-glucose (TyG) index is a reliable marker for insulin resistance.
• Previous studies often analyzed the TyG index in isolation.

Purpose of the Study:

• To characterize the endocrine-metabolic architecture associated with the TyG index in patients with thyroid dysfunction.
• To utilize a systems-phenotyping approach to understand metabolic health.
• To evaluate the TyG index as a descriptor of metabolic patterns.

Main Methods:

• Retrospective, single-center, cross-sectional study of 387 adults with thyroid dysfunction.
• Unsupervised clustering (PCA, K-means, GMM, Ward) of metabolic variables (glucose, lipids, BMI, liver enzymes).
• Analysis of TyG index, latent profile analysis, and Gaussian graphical models (GGM).

Main Results:

• Three distinct, overlapping metabolic phenotypes identified: metabolically preserved (MP), intermediate hepatic-dominant (IHD), and severe insulin-resistance-dominant (SIRD).
• TyG index values increased monotonically across phenotypes (MP: 8.24, IHD: 8.74, SIRD: 8.87; p < 0.001).
• Metabolic and thyroid variables formed near-orthogonal blocks in the GGM analysis.

Conclusions:

• Systems phenotyping revealed three interpretable metabolic partitions along a continuum in thyroid dysfunction patients.
• The TyG index serves as a pragmatic, single-number summary of the metabolic gradient.
• Hepatic dysregulation may be an early stage of insulin resistance, and thyroid autoimmunity acts as a parallel modulator.