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Cited by 92Gestational Diabetes Research and ManagementThyroid Disorders and TreatmentsGrowth Hormone and Insulin-like Growth Factors

A longitudinal study of thyroid markers across pregnancy and the risk of gestational diabetes

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Rawal, Shristi, Tsai, Michael Y, Hinkle, Stefanie N, Zhu, Yeyi, Bao, Wei, Lin, Yuan, Panuganti, Pranati, Albert, Paul S +2 more·2018·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2017-02442PMC PMC6276672
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Abstract

Context: T3 is the biologically active thyroid hormone involved in glucose metabolism. The free T3 (fT3)/free T4 (fT4) ratio, a marker indicating conversion of fT4 to fT3, is also implicated in glucose homeostasis. Objective: To examine associations of fT3 and the fT3/fT4 ratio with gestational diabetes mellitus (GDM). Design: In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and the fT3/fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10 to 14) and second (weeks 15 to 26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk. Setting: Twelve US clinical centers. Participants: One hundred seven GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2802 women. Main Outcome Measures: GDM diagnosis ascertained from medical records. Results: Both fT3 and the fT3/fT4 ratio were positively associated with GDM: adjusted OR (95% CI) comparing the highest vs lowest fT3 quartile was 4.25 (1.67, 10.80) at the first trimester and 3.89 (1.50, 10.10) at the second trimester. Similarly, the corresponding risk estimates for the fT3/fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at the first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Conclusions: Higher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.

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  1. [2]2. Toulis KA, Stagnaro-Green A, Negro R. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta-analysis. Endocr Pract. 2014;20(7):703–714. [DOI] [PubMed] [Google Scholar]
  2. [3]3. Sahu MT, Das V, Mittal S, Agarwal A, Sahu M. Overt and subclinical thyroid dysfunction among Indian pregnant women and its effect on maternal and fetal outcome. Arch Gynecol Obstet. 2010;281(2):215–220. [DOI] [PubMed] [Google Scholar]
  3. [4]4. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol. 2012;119(5):983–988. [DOI] [PubMed] [Google Scholar]
  4. [5]5. Ying H, Tang YP, Bao YR, Su XJ, Cai X, Li YH, Wang DF. Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus. Endocrine. 2016;54(3):742–750. [DOI] [PubMed] [Google Scholar]
  5. [6]6. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, Luthy D, Gross S, Bianchi DW, D’Alton ME. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol. 2008;112(1):85–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. [7]7. Männistö T, Vääräsmäki M, Pouta A, Hartikainen AL, Ruokonen A, Surcel HM, Bloigu A, Järvelin MR, Suvanto E. Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life. J Clin Endocrinol Metab. 2010;95(3):1084–1094. [DOI] [PubMed] [Google Scholar]
  7. [8]8. Chen LM, Du WJ, Dai J, Zhang Q, Si GX, Yang H, Ye EL, Chen QS, Yu LC, Zhang C, Lu XM. Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population. PLoS One. 2014;9(10):e109364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. [9]9. Oguz A, Tuzun D, Sahin M, Usluogullari AC, Usluogullari B, Celik A, Gul K. Frequency of isolated maternal hypothyroxinemia in women with gestational diabetes mellitus in a moderately iodine-deficient area. Gynecol Endocrinol. 2015;31(10):792–795. [DOI] [PubMed] [Google Scholar]
  9. [10]10. Yang S, Shi FT, Leung PC, Huang HF, Fan J. Low thyroid hormone in early pregnancy is associated with an increased risk of gestational diabetes mellitus. J Clin Endocrinol Metab. 2016;101(11):4237–4243. [DOI] [PubMed] [Google Scholar]
  10. [11]11. Agarwal MM, Dhatt GS, Punnose J, Bishawi B, Zayed R. Thyroid function abnormalities and antithyroid antibody prevalence in pregnant women at high risk for gestational diabetes mellitus. Gynecol Endocrinol. 2006;22(5):261–266. [DOI] [PubMed] [Google Scholar]
  11. [12]12. Casey BM, Dashe JS, Spong CY, McIntire DD, Leveno KJ, Cunningham GF. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol. 2007;109(5):1129–1135. [DOI] [PubMed] [Google Scholar]
  12. [13]13. Maia AL, Goemann IM, Meyer EL, Wajner SM. Type 1 iodothyronine deiodinase in human physiology and disease. Deiodinases: the balance of thyroid hormone. J Endocrinol. 2011;209(3):283–297. [DOI] [PubMed] [Google Scholar]
  13. [14]14. Haddow JE, Craig WY, Neveux LM, Palomaki GE, Lambert-Messerlian G, Malone FD, D’Alton ME; First and Second Trimester Risk of Aneuploidy (FaSTER) Research Consortium . Free thyroxine during early pregnancy and risk for gestational diabetes. PLoS One. 2016;11(2):e0149065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. [15]15. Nicoloff JT, Lum SM, Spencer CA, Morris R. Peripheral autoregulation of thyroxine to triiodothyronine conversion in man. Horm Metab Res Suppl. 1984;14:74–79. [PubMed] [Google Scholar]
  15. [16]16. Keck FS, Loos U. Peripheral autoregulation of thyromimetic activity in man. Horm Metab Res. 1988;20(2):110–114. [DOI] [PubMed] [Google Scholar]
  16. [17]17. Bassols J, Prats-Puig A, Soriano-Rodríguez P, García-González MM, Reid J, Martínez-Pascual M, Mateos-Comerón F, de Zegher F, Ibáñez L, López-Bermejo A. Lower free thyroxin associates with a less favorable metabolic phenotype in healthy pregnant women. J Clin Endocrinol Metab. 2011;96(12):3717–3723. [DOI] [PubMed] [Google Scholar]
  17. [18]18. Jing S, Xiaoying D, Ying X, Rui L, Mingyu G, Yuting C, Yanhua Y, Yufan W, Haiyan S, Yongde P. Different levels of thyroid hormones between impaired fasting glucose and impaired glucose tolerance: free T3 affects the prevalence of impaired fasting glucose and impaired glucose tolerance in opposite ways. Clin Endocrinol (Oxf). 2014;80(6):890–898. [DOI] [PubMed] [Google Scholar]
  18. [19]19. Knight BA, Shields BM, Hattersley AT, Vaidya B. Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters. Eur J Endocrinol. 2016;174(1):51–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. [21]21. Committee on Practice Bulletins—Obstetrics Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013;122(2 Pt 1):406–416. [DOI] [PubMed] [Google Scholar]
  20. [23]23. Karakosta P, Alegakis D, Georgiou V, Roumeliotaki T, Fthenou E, Vassilaki M, Boumpas D, Castanas E, Kogevinas M, Chatzi L. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab. 2012;97(12):4464–4472. [DOI] [PubMed] [Google Scholar]
  21. [24]24. Nair R, Mahadevan S, Muralidharan RS, Madhavan S. Does fasting or postprandial state affect thyroid function testing? Indian J Endocrinol Metab. 2014;18(5):705–707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [25]25. Scobbo RR, VonDohlen TW, Hassan M, Islam S. Serum TSH variability in normal individuals: the influence of time of sample collection. W V Med J. 2004;100(4):138–142. [PubMed] [Google Scholar]
  23. [26]26. Kamat V, Hecht WL, Rubin RT. Influence of meal composition on the postprandial response of the pituitary-thyroid axis. Eur J Endocrinol. 1995;133(1):75–79. [DOI] [PubMed] [Google Scholar]
  24. [27]27. Das DK, Bandyopadhyay D, Bandyopadhyay S, Neogi A. Thyroid hormone regulation of β-adrenergic receptors and catecholamine sensitive adenylate cyclase in foetal heart. Acta Endocrinol (Copenh). 1984;106(4):569–576. [DOI] [PubMed] [Google Scholar]
  25. [28]28. Kemp HF, Hundal HS, Taylor PM. Glucose transport correlates with GLUT2 abundance in rat liver during altered thyroid status. Mol Cell Endocrinol. 1997;128(1-2):97–102. [DOI] [PubMed] [Google Scholar]
  26. [29]29. Bakker SJ, ter Maaten JC, Popp-Snijders C, Heine RJ, Gans RO. Triiodothyronine: a link between the insulin resistance syndrome and blood pressure? J Hypertens. 1999;17(12 Pt 1):1725–1729. [DOI] [PubMed] [Google Scholar]
  27. [30]30. Ortega E, Koska J, Pannacciulli N, Bunt JC, Krakoff J. Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals. Eur J Endocrinol. 2008;158(2):217–221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. [32]32. Soldin OP, Tractenberg RE, Hollowell JG, Jonklaas J, Janicic N, Soldin SJ. Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency. Thyroid. 2004;14(12):1084–1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. [33]33. Moncayo R, Zanon B, Heim K, Ortner K, Moncayo H. Thyroid function parameters in normal pregnancies in an iodine sufficient population. BBA Clin. 2015;3:90–95. [DOI] [PMC free article] [PubMed] [Google Scholar] Articles from The Journal of Clinical Endocrinology and Metabolism are provided here courtesy of The Endocrine Society

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Authors
Rawal, S., Tsai, M. Y., Hinkle, S. N., Zhu, Y., Bao, W., Lin, Y., Panuganti, P., Albert, P. S., Ma, R. C. W., & Zhang, C.
Affiliations
  • Rutgers, The State University of New Jersey (US)
  • University of Minnesota (US)
  • National Institutes of Health (US)
  • Kaiser Permanente (US)
  • University of Iowa (US)
  • Division of Cancer Epidemiology and Genetics (US)
  • Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
Corresponding author
Zhang, Cuilin
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2018-06-07
Volume
103
Issue
7
Pages
2447-2456
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2017-02442
PMC
PMC6276672
OpenAlex
W2807234533
Cited by
92
References
4
Citations by year
2026: 10 · 2025: 16 · 2024: 10 · 2023: 10 · 2022: 19 · 2021: 12 · 2020: 12 · 2019: 3
FWCI
7.58
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Environmental Health Sciences (P30ES005605)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275200800012C, HHSN275200800002C, HHSN275200800014C, R21HD091458, HHSN275200800003C, HHSN275201000009C, HHSN275200800003I, HHSN275200800013C, HHSN275 200800028C, HHSN275200800002I, HHSN275201000001G, HHSN275201000001Z)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
gestational diabetes mellitus, free T3, thyroid hormones, thyroid autoimmunity, thyroid-stimulating hormone, free thyroxine, glucose metabolism, pregnancy, first and second trimester, GDM risk factors
MeSH terms
Adult, Female, Humans, Longitudinal Studies, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Second, Risk Factors, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine, Biomarkers, Logistic Models, Case-Control Studies, Diabetes, Gestational

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