Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2024; 15(10): 2081-2092
Published online Oct 15, 2024. doi: 10.4239/wjd.v15.i10.2081
Association between sensitivity to thyroid hormones and non-high-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus
Xiao-Ye Duan, Jun-Ling Fu, Li-Na Sun, Zhi-Jing Mu, Shuang-Ling Xiu
Xiao-Ye Duan, Jun-Ling Fu, Li-Na Sun, Zhi-Jing Mu, Shuang-Ling Xiu, Department of Endocrinology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
Author contributions: Duan XY analyzed the data and wrote the manuscript; Fu JL, Sun LN and Mu ZJ contributed to the data collection; Xiu SL contributed to the data interpretation and reviewed the manuscript; all the authors read and approved the submitted version of the manuscript.
Supported by the Xuanwu Hospital Capital Medical University Science Program for Fostering Young Scholars, No. YC20220113; and the Pilot Project for Public, No. Beijing Medical Research 2021-8.
Institutional review board statement: The study was reviewed and approved by the Research Ethics Boards at Xuanwu Hospital (CTR-2020075).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shuang-Ling Xiu, PhD, Doctor, Department of Endocrinology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Changchun Street, Beijing 100053, China. xiushuangling@126.com
Received: May 6, 2024
Revised: August 6, 2024
Accepted: August 30, 2024
Published online: October 15, 2024
Processing time: 143 Days and 2.8 Hours
Abstract
BACKGROUND

Dyslipidemia and type 2 diabetes mellitus (T2DM) are chronic conditions with substantial public health implications. Effective management of lipid metabolism in patients with T2DM is critical. However, there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population, particularly concerning non-high-density lipoprotein cholesterol (non-HDL-C).

AIM

To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.

METHODS

In this cross-sectional study, thyroid hormone sensitivity indices, the thyroid feedback quantile-based index (TFQI), the thyroid-stimulating hormone index (TSHI), the thyrotrophic T4 resistance index (TT4RI), and the free triiodothyronine (FT3)/free thyroxine (FT4) ratio were calculated. Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels. Random forest variable importance and Shapley Additive Explanations (SHAP) summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.

RESULTS

Among the 994 participants, 389 (39.13%) had high non-HDL-C levels. Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI (OR: 1.584; 95%CI: 1.088-2.304; P = 0.016), TSHI (OR: 1.238; 95%CI: 1.034-1.482; P = 0.02), and TT4RI (OR: 1.075; 95%CI: 1.006-1.149; P = 0.032) but was not significantly correlated with the FT3/FT4 ratio. The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex. An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men (OR: 1.331; 95%CI: 1.003-1.766; P = 0.048) but elevated TFQI levels in women (OR: 2.337; 95%CI: 1.4-3.901; P = 0.001). Among the analyzed variables, the average SHAP values were highest for TSHI, followed by TT4RI.

CONCLUSION

Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Keywords: Non-high-density lipoprotein cholesterol; Sensitivity to thyroid hormones; Type 2 diabetes mellitus; Thyroid feedback quantile-based index; Free triiodothyronine/free thyroxine ratio

Core Tip: Reduced central thyroid hormone sensitivity was an independent risk factor of high non-high-density lipoprotein cholesterol (non-HDL-C), even after adjusting for multiple confounding factors. The patients with hyper-non-HDL-C were more susceptible to metabolic disorders and impaired sensitivity to thyroid hormones. Meanwhile, the relationships between thyroid hormone sensitivity and non-HDL-C levels were different in male and female, indicating a gender-related regulation of thyroid hormones on serum non-HDL-C levels. This study may provide new evidence for the role of reduced thyroid hormone sensitivity for non-HDL-C levels and lie the groundwork for future therapeutic strategies for diabetes-related cardiovascular disease risk.