Free Triiodothyronine Concentrations and Gestational Diabetes Mellitus: Unveiling the Correlation and Implications

Abstract

Thyroid disease and gestational diabetes mellitus (GDM) are frequent complications during pregnancy. We observed the relationship between thyroid indicators and blood glucose to analyze whether thyroid function is associated with the development of GDM. We enrolled a total of 575 pregnant women diagnosed with GDM and 573 pregnant women without GDM. The correlation between thyroid indicators and blood glucose levels was established through correlation analysis. In addition, stratified analysis and restricted cubic spline curves were employed to describe the association between thyroid indicators and the incidence of GDM. We found no significant difference in urine iodine levels between the GDM and non-GDM groups throughout the second trimester. The levels of free triiodothyronine (FT3) and both fasting blood glucose and post-load blood glucose showed a robust positive connection. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4), on the other hand, showed a weakly positive connection with these glucose values. A nonlinear correlation between FT3 and the risk of GDM was also found (pNonlinear=0.0007, p<0.0001). Particularly, those in the top quartile of FT3 had a 6.99-fold greater risk than those in the lowest. Notably, FT3 levels below 4.04 pmol/l were linked to a decreased chance of developing GDM, but levels over 4.04 pmol/l were linked to a greater risk. Our study successfully established the correlation between thyroid indicators and the risk of GDM. Notably, we discovered a non-linear association between FT3 levels and GDM. The study suggests that ensuring optimal thyroid function during pregnancy may decrease the likelihood of developing GDM.

Keywords

gestational diabetes mellitus - thyroid function - free triiodothyronine

Publication History

Received: 15 September 2023

Accepted after revision: 07 December 2024

Article published online:
10 February 2025

• References

• 1 McIntyre HD, Catalano P, Zhang C. et al. Gestational diabetes mellitus. Nat Rev Dis Primers 2019; 5: 47
• 2 Gao C, Sun X, Lu L. et al. Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis. J Diabetes Invest 2019; 10: 154-162
• 3 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27: 315-389
• 4 Rawal S, Tsai MY, Hinkle SN. et al. A longitudinal study of thyroid markers across pregnancy and the risk of gestational diabetes. J Clin Endocr Metab 2018; 103: 2447-2456
• 5 Tudela CM, Casey BM, McIntire DD. et al. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012; 119: 983-988
• 6 Maleki N, Tavosi Z. Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis. Diabetic Med 2015; 32: 206-212
• 7 Männistö T, Mendola P, Grewal J. et al. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endcor Metab 2013; 98: 2725-2733
• 8 Chen LM, Du WJ, Dai J. et al. Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population. Plos One 2014; 9: e109364
• 9 Neven KY, Cox B, Cosemans C. et al. Lower iodine storage in the placenta is associated with gestational diabetes mellitus. BMC Med 2021; 19: 47
• 10 Bell GA, Männistö T, Liu A. et al. The joint role of thyroid function and iodine concentration on gestational diabetes risk in a population-based study. Acta Obstet Gyn Scan 2019; 98: 500-506
• 11 Chidakel A, Mentuccia D, Celi FS. Peripheral metabolism of thyroid hormone and glucose homeostasis. Thyroid 2005; 15: 899-903
• 12 Raets L, Minschart C, Van den Bruel A. et al. Higher thyroid fT3-to-fT4 ratio is associated with gestational diabetes mellitus and adverse pregnancy outcomes. J Clin Med 2022; 11: 5016
• 13 Wu JN, Pérez-López FR, Peng T. et al. Association of early pregnancy free and total triiodothyronine with the subsequent risk of gestational diabetes mellitus. Endcor Pract 2023; 29: 40-47
• 14 Liu ZM, Li G, Wu Y. et al. Increased central and peripheral thyroid resistance indices during the first half of gestation were associated with lowered risk of gestational diabetes-analyses based on Huizhou birth cohort in south China. Front Endocrinol 2022; 13: 806256
• 15 Agarwal MM, Dhatt GS, Punnose J. et al. Thyroid function abnormalities and antithyroid antibody prevalence in pregnant women at high risk for gestational diabetes mellitus. Gynecol Endocrinol 2006; 22: 261-266
• 16 Karakosta P, Alegakis D, Georgiou V. et al. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocr Metab 2012; 97: 4464-4472
• 17 Taylor PN, Razvi S, Pearce SH. et al. Clinical review: a review of the clinical consequences of variation in thyroid function within the reference range. J Clin Endocr Metab 2013; 98: 3562-3571
• 18 Haddow JE, Craig WY, Palomaki GE. et al. Impact of adjusting for the reciprocal relationship between maternal weight and free thyroxine during early pregnancy. Thyroid 2013; 23: 225-230
• 19 Haddow JE, Neveux LM, Palomaki GE. et al. An inverse relationship between weight and free thyroxine during early gestation among women treated for hypothyroidism. Thyroid 2015; 25: 949-953
• 20 Knight BA, Shields BM, Hattersley AT. et al. Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters. Eur J Endocrinol 2016; 174: 51-57
• 21 Leng J, Li W, Wang L. et al. Higher thyroid-stimulating hormone levels in the first trimester are associated with gestational diabetes in a Chinese population. Diabetic Med 2019; 36: 1679-1685
• 22 Yang S, Shi FT, Leung PC. et al. Low Thyroid hormone in early pregnancy is associated with an increased risk of gestational diabetes mellitus. J Clin Endocr Metab 2016; 101: 4237-4243
• 23 Plowden TC, Schisterman EF, Sjaarda LA. et al. Thyroid-stimulating hormone, anti-thyroid antibodies, and pregnancy outcomes. Am J Obstet Gunecol 2017; 217: 691-697
• 24 Zhang Y, Sun W, Zhu S. et al. The impact of thyroid function and TPOAb in the first trimester on pregnancy outcomes: A retrospective study in Peking. J Clin Endocr Metab 2020; 105: dgz167
• 25 Beumer W, Effraimidis G, Drexhage RC. et al. Changes in serum adhesion molecules, chemokines, cytokines, and tissue remodeling factors in euthyroid women without thyroid antibodies who are at risk for autoimmune thyroid disease: a hypothesis on the early phases of the endocrine autoimmune reaction. J Clin Endocr Metab 2013; 98: 2460-2468
• 26 Jia M, Wu Y, Lin B. et al. Meta-analysis of the association between maternal subclinical hypothyroidism and gestational diabetes mellitus. Int J Gynecol Obstet 2019; 144: 239-247
• 27 Tang L, Li P, Zhou H. et al. A longitudinal study of thyroid markers during pregnancy and the risk of gestational diabetes mellitus and post-partum glucose metabolism. Diabetes Metab Res 2021; 37: e3441
• 28 Huang K, Xu Y, Yan S. et al. Isolated effect of maternal thyroid-stimulating hormone, free thyroxine and antithyroid peroxidase antibodies in early pregnancy on gestational diabetes mellitus: a birth cohort study in China. Endocr J 2019; 66: 223-231
• 29 Zha H, Yu L, Tang Y. et al. Effect of iodine nutrition status on thyroid function and pregnancy outcomes. Biol Trace Elem Res 2023; 201: 5143-5151