Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Department of Preventive Medicine, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
Thyroid. 2022 Jun;32(6):694-704. doi: 10.1089/thy.2021.0533. Epub 2022 May 24.
There are conflicting data regarding the association of thyroid function with incident diabetes. We prospectively investigated thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and its conversion ratio (fT3:fT4) with the risk of developing diabetes in euthyroid subjects and those with subclinical thyroid dysfunction. Our hypothesis is that this relationship is a U-shaped curve since both subclinical thyroid diseases may be associated with diabetes. ELSA-Brasil is a highly admixed cohort study of 35-74 years old at baseline (2008-2010). Levels of TSH, fT4, fT3, and fT3:fT4 ratio were evaluated at baseline and incident diabetes was estimated over an 8.2-year follow-up (2017-2019). Diabetes was identified based on medical diagnosis, prescriptions, and laboratory tests. The risk of diabetes was evaluated according to quintiles of TSH, fT4, fT3, and fT3:fT4 ratio using Poisson regression with robust variance presented as relative risk (RR) with confidence interval [CI] of 95% after multivariable adjustment for sociodemographic and cardiovascular risk factors (reference third quintile), and as continuous variables. We included 7948 participants (mean age, 50.2 [standard deviation 8.6] years; 54.4% female): 7177 euthyroid, 726 with subclinical hypothyroidism, and 45 with subclinical hyperthyroidism. Incidence of diabetes was 14.8%. No association was found for TSH, fT4, fT3, and fT3:fT4 ratio quintiles with incident diabetes. Using continuous variables, the increase of 1-unit (1-U) of fT4 decreased the risk of diabetes (RR 0.94 [CI 0.91-0.99]), while the increase of 1-U of the fT3:fT4 ratio increased the diabetes risk (RR 1.37 [CI 1.15-1.63]). The increase of 1-U of fT3 was associated with an increased risk of diabetes, but without significance after multivariable adjustment. In body mass index-stratified analysis, people with overweight or obesity presented a modest significantly higher risk of diabetes in the lowest quintile of fT4 (RR 1.04 [CI 1.01-1.07]) and an inverse association with incident diabetes in the first quintile of fT3:fT4 ratio (RR, 0.95 [CI 0.93-0.98]). The analyses using continuous variables presented similar findings. These findings suggest that fT4 and fT3 levels and the conversion rate might be additional risk factors associated with incident diabetes, especially in the presence of overweight or obesity. However, they need to be confirmed in future studies. (ClinicalTrials.gov Identifier: NCT02320461).
关于甲状腺功能与糖尿病发病之间的关联，存在相互矛盾的数据。我们前瞻性地研究了促甲状腺激素（TSH）、游离甲状腺素（fT4）、游离三碘甲状腺原氨酸（fT3）及其转化率（fT3：fT4）与甲状腺功能正常者和亚临床甲状腺功能减退症患者发生糖尿病的风险。我们的假设是，这种关系呈 U 型曲线，因为这两种亚临床甲状腺疾病都可能与糖尿病有关。ELSA-Brasil 是一项针对 35-74 岁人群的高度混合队列研究，基线（2008-2010 年）。在基线和 8.2 年随访（2017-2019 年）期间评估了 TSH、fT4、fT3 和 fT3：fT4 比值。根据医学诊断、处方和实验室检查来确定糖尿病。根据 TSH、fT4、fT3 和 fT3：fT4 比值的五分位数，使用泊松回归评估糖尿病的风险，采用稳健方差表示相对风险（RR），置信区间 [CI] 为 95%，经多变量调整后，将社会人口统计学和心血管危险因素（参考第三五分位数）作为连续变量。我们纳入了 7948 名参与者（平均年龄 50.2[8.6]岁；54.4%为女性）：7177 名甲状腺功能正常，726 名亚临床甲状腺功能减退，45 名亚临床甲状腺功能亢进。糖尿病的发病率为 14.8%。TSH、fT4、fT3 和 fT3：fT4 比值五分位数与糖尿病发病无关。使用连续变量，fT4 增加 1 个单位（1-U）可降低糖尿病风险（RR 0.94[CI 0.91-0.99]），而 fT3：fT4 比值增加 1-U 会增加糖尿病风险（RR 1.37[CI 1.15-1.63]）。fT3 增加与糖尿病风险增加相关，但多变量调整后无统计学意义。在体重指数分层分析中，超重或肥胖人群的 fT4 最低五分位数的糖尿病风险显著升高（RR 1.04[CI 1.01-1.07]），而 fT3：fT4 比值的第一个五分位数与糖尿病发病呈负相关（RR，0.95[CI 0.93-0.98]）。使用连续变量的分析得出了类似的发现。这些发现表明，fT4 和 fT3 水平和转化率可能是与糖尿病发病相关的其他危险因素，尤其是在超重或肥胖的情况下。然而，它们需要在未来的研究中得到证实。（临床试验.gov 标识符：NCT02320461）。
