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). 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.