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



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.



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 μIU/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 μIU/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.



Individual changes in TSH and thyroid hormones, even within the normal reference range, were an additional risk factor of incident T2DM.
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Ji Eun
JE
Jun
2 Department of Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Jae Hwan
JH
Jee
3 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon, Republic of Korea.
Ji Cheol
JC
Bae
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Sang-Man
SM
Jin
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Kyu Yeon
KY
Hur
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Moon-Kyu
MK
Lee
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Tae Hyuk
TH
Kim
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Sun Wook
SW
Kim
1 Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.
Jae Hyeon
JH
Kim
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
euthyroid; free thyroxine; thyrotropin; triiodothyronine; type 2 diabetes mellitus