Impaired sensitivity to thyroid hormones is associated with high lipoprotein(a) level in euthyroid patients with type 2 diabetes mellitus

Abstract

Background: The relationship between thyroid hormone sensitivity and lipoprotein(a) (Lp(a)) is unclear. The purpose of this study is to illuminate the correlation between thyroid hormone sensitivity and Lp(a) in euthyroid patients with type 2 diabetes mellitus (T2DM).

Method: A cross-sectional study was conducted on 1097 patients with T2DM. The 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. Linear and binary logistic regression analysis were performed to assess the relationship between thyroid hormone sensitivity indices and Lp(a). Restricted cubic splines were also used to evaluate the association between thyroid hormone sensitivity indices and Lp(a).

Result: Among the 1097 participants, the percentage of Lp(a)≥30 mg/dL was 20.3%. Linear regression analysis revealed that TFQI displayed a positive correlation with Lp(a) levels, whereas the FT3/FT4 ratio exhibited a negative correlation. The adjusted odds ratio (aOR)(95% confidence interval(CI)) for high Lp(a) level was increased with rising TFQI quartiles(Q3: aOR 1.49,95% CI 1.09-2.06; Q4: aOR 1.74, 95% CI 1.36-2.23) (P<0.05),with Q1 as the reference. By contrast,the aOR(95% CI) for high Lp(a) level was decreased with rising FT3/FT4 ratio quartiles (P<0.05). The robustness of these findings was further confirmed by restricted cubic spline analysis.

Conclusion: In euthyroid T2DM patients, decreased sensitivity to thyroid hormones was found to be linked with high Lp(a) level. Screening for thyroid hormone insensitivity and serum Lp(a) levels should be emphasized in euthyroid T2DM patients for early intervention and improved outcomes.

Keywords: free triiodothyronine/free thyroxine ratio; lipoprotein(a); sensitivity to thyroid hormones; thyroid feedback quantile-based index; type 2 diabetes mellitus.

Figure 1

The flow of participants through the trial.

Figure 2

The levels of Lp(a) and the prevalence of T2DM patients with high Lp(a) level across the quartiles of thyroid parameters. (A) The levels of Lp(a) across the FT3/FT4 ratio quartiles. (B) The levels of Lp(a) across the TFQI quartiles. (C) The prevalence of T2DM patients with high Lp(a) level across the FT3/FT4 ratio quartiles. (D) The prevalence of T2DM patients with high Lp(a) level across the TFQI quartiles. Q1, the 1^st quartiles; Q2, the 2^nd quartiles; Q3, the 3^rd quartiles; Q4, the 4^th quartiles; Lp(a), lipoprotein(a); NS, P>0.05; FT3, Free Triiodothyronine; FT4, Free Thyroxine; TFQI, Thyroid feedback quantile-based index; T2DM, type 2 diabetes mellitus.

Figure 3

The forest maps of logistic regression analysis for the association between high Lp(a) level and quartiles of FT3/FT4 ratio and TFQI, with the 1^st quartile as the reference. (A) The ORs for high Lp(a) level across FT3/FT4 ratio quartiles. (B) The ORs for high Lp(a) level across TFQI quartiles. Model was adjusted for age, sex, BMI, DR, AST, eGFR, TG and HDL-C. Q1, the 1^st quartiles; Q2, the 2^nd quartiles;Q3, the 3^rd quartiles;Q4, the 4^th quartiles; Lp(a), lipoprotein(a); BMI, body mass index; DR, diabetic retinopathy; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; FT3, Free Triiodothyronine; FT4, Free Thyroxine; TFQI, Thyroid feedback quantile-based index.

Figure 4

Restricted spline curve of the FT3/FT4 ratio and TFQI odds ratio of high Lp(a) level after adjusting for the covariates including Age, gender, BMI, TG,HDL-C,DR,AST and eGFR. (A) The restricted spline curve of the FT3/FT4 ratio odds ratio of high Lp(a) level. (B) The restricted spline curve of the TFQI odds ratio of high Lp(a) level. Abbreviations: Lp(a), lipoprotein(a); BMI, body mass index; DR, diabetic retinopathy; AST,aspartate aminotransferase; eGFR, estimated glomerular filtration rate; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; FT3, Free Triiodothyronine; FT4, Free Thyroxine; TFQI, Thyroid feedback quantile-based index.