Association between central thyroid hormone sensitivity and prediabetes: Tehran thyroid study

Front Endocrinol (Lausanne). 2025 Jun 17:16:1534058. doi: 10.3389/fendo.2025.1534058. eCollection 2025.

Abstract

Background: Thyroid hormone sensitivity indices represent a recently proposed clinical entity related to metabolic health outcomes. The link between thyroid hormone sensitivity and prediabetes is not clear. This population-based study investigated the association between thyroid hormone sensitivity indices and prediabetes.

Methods: Among 5,783 participants over 20 years, after excluding those receiving thyroid medications or corticosteroid drugs, having thyroid surgery, having a history of cancer, pregnant women, and those with end-stage renal disease, 4,356 subjects were included in the study. The odds ratio (OR) and 95% confidence interval (95%CI) for prediabetes in the general and euthyroid population per 1-SD increase in thyroid hormone resistance indices (PFTQI, TSHI, and lnTT4RI) were reported with logistic regression models.

Results: One SD increase in PTFQI was significantly associated with lower odds of prediabetes even after total adjustment (OR:0.88; 95%CI: 0.82-0.94). The association was observed in women, non-smokers, and those with negative anti-thyroid peroxidase antibodies. In the euthyroid subgroup, one SD increase in PTFQI, TSHI, and lnTT4RI showed lower odds of prediabetes and [PTFQI: 0.89 (95%CI: 0.83-0.97); TSHI: 0.83 (95%CI: 0.74-0.94); lnTT4RI: 0.83 (95%CI: 0.74-0.93)]. We also found a negative correlation between thyroid hormone sensitivity indices and fasting plasma glucose (PTFQI: r =-0.094, TSHI:-0.1, and lnTT4RI: r =-0.098) and 2-h post-challenge glucose (PTFQI: r =-0.096, TSHI:-0.054, and lnTT4RI: r =-0.031).

Conclusion: Lower central sensitivity to thyroid hormone, as represented by increased TSHI, TT4RI, and PTFQI, is associated with a lower risk of prediabetes, even in euthyroid individuals.

Keywords: parametric thyroid feedback quantile-based index; prediabetes; thyroid function; thyroid hormone resistance; thyroid-stimulating hormone index; thyrotrophic thyroxin resistance index.

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Humans
  • Iran / epidemiology
  • Male
  • Middle Aged
  • Prediabetic State* / blood
  • Prediabetic State* / epidemiology
  • Prediabetic State* / metabolism
  • Thyroid Gland* / metabolism
  • Thyroid Hormone Resistance Syndrome* / blood
  • Thyroid Hormone Resistance Syndrome* / epidemiology
  • Thyroid Hormones* / blood
  • Thyroid Hormones* / metabolism

Substances

  • Thyroid Hormones