Supplementary Material for: Higher Sensitivity to Thyroid Hormones may be Linked to Maintaining the Healthy Metabolic Condition in Population with Obesity: New Insight from NHANES

Introduction: Obesity contributes to the pathogenesis of diverse metabolic diseases, and yet the mechanism underlying metabolically healthy obesity (MHO) remains elusive. Thyroid hormones and sensitivity to them have a major impact on human metabolism. Our study investigated whether MHO is associated with thyroid hormone sensitivity. Methods: Thyroid hormone indices, including the thyroid stimulating hormone (TSH) index (TSHI), the thyrotroph thyroxine sensitivity index (TTSI), the thyroid feedback quantile-based index (TFQI), and the parametric thyroid feedback quantile-based Index (PTFQI), were calculated based on a non-institutionalized U.S. sample in the National Health and Nutrition Examination Survey (NHANES, 2007–2012). Participants were divided into four groups (metabolically healthy non-obesity [MHNO], metabolically unhealthy non-obesity [MUNO], MHO, and metabolically unhealthy obesity [MUO]) according to their body mass index and metabolic profiles. Linear regression, logistic regression, and restricted cubic splines were used to study the association between thyroid hormone indices and metabolic phenotypes. Results: A total of 4,857 participants (49.6% men; mean age, 42.6 years) were included. Of these, 1,539 had obesity and 235 were identified as having MHO. Compared with the MHNO group, participants with MHO had a lower level of TSH, TSHI, TTSI, TFQI, and PTFQI (all P < 0.05), but the differences among MHNO, MUNO, and MUO were not significant (all P > 0.05). Among the participants with obesity, TSH, TSHI, TTSI, TFQI, and PTFQI were positively associated with metabolic abnormality (all P < 0.05). Discussion/Conclusion: The MHO population exhibited higher thyroid hormone sensitivity among various obesity phenotypes, even when compared to those with MHNO. A positive association was observed between metabolic abnormality and thyroid hormone sensitivity, while the trend of TSH was observed to be consistent with sensitivity to thyroid hormone indices in discriminating metabolic abnormality. Hence, TSH has potential as a convenient index for detecting sensitivity to thyroid hormone and further metabolic conditions.

引言：肥胖是多种代谢性疾病的发病机制之一，但代谢健康型肥胖（metabolically healthy obesity, MHO）的潜在发病机制仍不明确。甲状腺激素及其敏感性对人体代谢具有重要调控作用。本研究旨在探讨代谢健康型肥胖与甲状腺激素敏感性是否存在关联。
方法：基于2007-2012年美国国家健康与营养检查调查（National Health and Nutrition Examination Survey, NHANES）的非机构化社区人群样本，计算多项甲状腺激素相关指标，包括促甲状腺激素（thyroid stimulating hormone, TSH）指数（TSHI）、垂体促甲状腺细胞甲状腺素敏感性指数（thyrotroph thyroxine sensitivity index, TTSI）、基于分位数的甲状腺反馈指数（thyroid feedback quantile-based index, TFQI）以及参数化基于分位数的甲状腺反馈指数（parametric thyroid feedback quantile-based index, PTFQI）。根据体质量指数与代谢特征，将受试者分为四组：代谢健康非肥胖组（metabolically healthy non-obesity, MHNO）、代谢异常非肥胖组（metabolically unhealthy non-obesity, MUNO）、代谢健康型肥胖组（MHO）以及代谢异常肥胖组（metabolically unhealthy obesity, MUO）。采用线性回归、logistic回归及限制性立方样条分析，探究甲状腺激素指标与代谢表型之间的关联。
结果：最终纳入4857名受试者，其中男性占比49.6%，平均年龄42.6岁。1539名受试者符合肥胖标准，235名被判定为代谢健康型肥胖。与代谢健康非肥胖组相比，代谢健康型肥胖组受试者的TSH、TSHI、TTSI、TFQI及PTFQI水平均更低（所有P<0.05）；而代谢健康非肥胖组、代谢异常非肥胖组与代谢异常肥胖组之间的上述指标差异均无统计学意义（所有P>0.05）。在肥胖受试者中，TSH、TSHI、TTSI、TFQI及PTFQI水平与代谢异常呈正相关（所有P<0.05）。
讨论/结论：在各类肥胖表型中，代谢健康型肥胖人群的甲状腺激素敏感性更高，甚至高于代谢健康非肥胖人群。代谢异常与甲状腺激素敏感性呈正相关；在区分代谢异常方面，促甲状腺激素的变化趋势与各类甲状腺激素敏感性指标的变化趋势一致。因此，促甲状腺激素有望成为便捷的甲状腺激素敏感性检测指标，进而用于评估后续代谢状态。