Thyroid Hormones and Type 2 Diabetes Mellitus: A Narrative Review of Findings From 18 Years of Follow-up in the Tehran Thyroid Study

Abstract

Context: Thyroid dysfunction and type 2 diabetes mellitus (T2DM) are common endocrine disorders with substantial public health implications. Increasing evidence suggests that alterations in thyroid function may influence glycemic regulation and the risk of T2DM. However, long-term population-based evidence on this relationship remains limited. Therefore, this study aimed to summarize the association between thyroid function and T2DM using findings from the Tehran Thyroid Study (TTS), a large community-based cohort with nearly 2 decades of follow-up. Evidence Acquisition: A literature search was performed in PubMed, Scopus, Web of Science, and the library of the Research Institute for Endocrine Sciences to identify articles within the TTS framework. The retrieved articles were categorized according to their primary predictors and outcomes, including T2DM, thyroid function, thyroid hormone sensitivity, and insulin resistance. Results: Over 18 years, a longitudinal analysis of 1938 adults showed that each unit increase in log-transformed thyroid-stimulating hormone (TSH) was associated with a 25% lower risk of developing T2DM (HR, 0.75; 95% CI, 0.64 - 0.90), whereas higher free thyroxine (FT4) levels were associated with a slightly increased risk of T2DM. Cross-sectional data indicated that overt and subclinical hyperthyroidism significantly increased the odds of hyperglycemia, with the highest prevalence (31.3%) observed in subclinical hyperthyroidism. In studies of thyroid hormone sensitivity, a 1-SD increase in the thyroid feedback quantile-based index (TFQI) was associated with higher odds of T2DM, whereas higher central sensitivity indices were associated with lower odds of prediabetes. Lower FT4 levels were independently associated with higher insulin resistance in euthyroid men but not in women. Patients with diabetes had a higher prevalence of subclinical hyperthyroidism but a lower incidence of thyroid dysfunction compared with controls. Conclusions: Trends toward lower TSH or relatively higher FT4 levels are associated with an increased incidence of T2DM. Both overt and subclinical hyperthyroidism are associated with hyperglycemia. Current evidence supports targeted metabolic monitoring in individuals with thyroid hormone excess or altered thyroid sensitivity indices but does not justify routine thyroid-directed therapy solely to prevent T2DM.