Bakker S J, ter Maaten J C, Popp-Snijders C, Slaets J P, Heine R J, Gans R O
Department of Internal Medicine, University Hospital Groningen, 9700 RB Groningen.
J Clin Endocrinol Metab. 2001 Mar;86(3):1206-11. doi: 10.1210/jcem.86.3.7324.
High levels of TSH are associated with an increased cardiovascular risk. Many cardiovascular risk factors cluster within the insulin resistance syndrome. It is not known whether levels of TSH cluster as well. We conducted this research to test the hypothesis that TSH, insulin sensitivity, and levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are interdependent in euthyroid subjects. Levels of TSH, free thyroid hormone, and serum lipids were measured in fasting serum samples taken before performance of a hyperinsulinemic euglycemic clamp to assess insulin sensitivity in 46 healthy euthyroid subjects with a mean TSH of 1.8 +/- 0.7 mU/L. Significant age- and sex-adjusted partial correlations of TSH with LDL-C (r = 0.48; P < 0.01) and HDL-C (r = -0.36; P < 0.05) were observed. TSH was not significantly correlated with insulin sensitivity or fasting triglyceride concentrations. In line with these results, we found the associations of TSH with LDL-C and HDL-C to be independent of insulin sensitivity. However, we observed significant effect-modification of the association of TSH with LDL-C by insulin sensitivity (P = 0.02). This effect-modification implies a range of associations of TSH with LDL-C that varies from absent in insulin-sensitive subjects to strongly positive in insulin-resistant subjects. We conclude that the increased cardiovascular risk associated with subclinical hypothyroidism seems to extend itself into the normal range of thyroid function. Importantly, the effect-modification of the association of TSH with LDL-C by insulin sensitivity suggests that insulin-resistant subjects are most susceptible to this increased risk.
促甲状腺激素（TSH）水平升高与心血管风险增加相关。许多心血管危险因素聚集在胰岛素抵抗综合征中。目前尚不清楚TSH水平是否也会聚集。我们开展这项研究以检验以下假设：在甲状腺功能正常的受试者中，TSH、胰岛素敏感性以及低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平相互依赖。在对46名甲状腺功能正常的健康受试者进行高胰岛素正常血糖钳夹试验以评估胰岛素敏感性之前，采集空腹血清样本，测定TSH、游离甲状腺激素和血脂水平，这些受试者的平均TSH为1.8±0.7 mU/L。观察到经年龄和性别校正后，TSH与LDL-C（r = 0.48；P < 0.01）和HDL-C（r = -0.36；P < 0.05）存在显著的偏相关性。TSH与胰岛素敏感性或空腹甘油三酯浓度无显著相关性。与这些结果一致，我们发现TSH与LDL-C和HDL-C的关联独立于胰岛素敏感性。然而，我们观察到胰岛素敏感性对TSH与LDL-C的关联有显著的效应修正作用（P = 0.02）。这种效应修正意味着TSH与LDL-C的关联范围有所不同，从胰岛素敏感受试者中不存在到胰岛素抵抗受试者中呈强阳性。我们得出结论，与亚临床甲状腺功能减退相关的心血管风险增加似乎延伸至甲状腺功能的正常范围。重要的是，胰岛素敏感性对TSH与LDL-C关联的效应修正表明，胰岛素抵抗受试者最易受这种风险增加的影响。
