Association Between Changes in Thyroid Hormones and Incident Type 2 Diabetes: A Seven-Year Longitudinal Study

Background: Thyroid hormones are important regulators of glucose homeostasis. However, the association between thyroid hormones within the reference range and type 2 diabetes mellitus (T2DM) remains unclear. The aim of this study was to clarify the incidence of T2DM according to the baseline levels and changes of thyrotropin (TSH) and thyroid hormones (free thyroxine and triiodothyronine) in euthyroid subjects. Methods: Among the participants who consecutively underwent thyroid function tests between 2006 and 2012 through a yearly health checkup program, 6235 euthyroid subjects (3619 men and 2616 women) without T2DM were enrolled in the study. The change in each hormone was calculated by subtracting the baseline value from the level at the end of follow-up or one year before the diagnosis of diabetes. Results: During 25,692 person-years of follow-up, there were 229 new cases of T2DM. After full adjustment for potential confounders including HbA1c and fasting glucose in Cox proportional hazards models, the individuals in the highest tertile of TSH change (2.5-4.2 mu IU/mL) had a greater risk of incident T2DM (hazard ratio [HR] = 1.44 [confidence interval (CI) 1.04-1.98], p = 0.027) in comparison with individuals in the lowest tertile (-4.1 to -0.5 mu IU/mL). Simultaneously, the highest tertile of triiodothyronine change (16.3-104.7 ng/dL) and free thyroxine change (0.2-1.6 ng/dL) conferred protective effects against diabetes (HR = 0.60 [CI 0.43-0.85], p = 0.002, and HR=0.34 [CI 0.24-0.48], p < 0.001, respectively) compared with those in the lowest tertile (-76.5 to -1.8 ng/dL and -0.6 to 0.0 ng/dL, respectively). These associations remained significant when each of the hormones was analyzed as a continuous variable. However, baseline levels or tertiles of TSH and thyroid hormones were not associated with the risk of diabetes. Conclusions: Individual changes in TSH and thyroid hormones, even within the normal reference range, were an additional risk factor of incident T2DM.