{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:12:07Z","timestamp":1792501927250,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002402","name":"Sun Yat-sen University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The study aimed to explore the relationship of thyroid function and resistance indices with subsequent risk of gestational diabetes (GDM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>This was a longitudinal study embedded in the Huizhou Birth Cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 2,927 women of singleton pregnancy were recruited from January to October of 2019. Thyroid central resistance indices were evaluated by Thyroid Feedback Quartile-Based index (TFQI), Thyrotrophy T4 Resistance Index (TT4RI), and TSH Index (TSHI) based on plasma-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels during the first half of pregnancy. Thyroid peripheral sensitivity was assessed by free triiodothyronine (FT3) to FT4 ratio (FT3\/FT4), a proxy of deiodinase activity. GDM was diagnosed between 24 and 28 weeks of gestation by a standardized 75 g oral glucose tolerance test. Multivariable linear and logistic regression was applied to examine the associations of thyroid markers with GDM risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FT3 and FT3\/FT4 were positively associated with both fasting and post-load glucose levels, while TSH, TSHI, TT4RI, and TFQI were negatively associated with 1 and 2 h post-load glucose levels. Compared with the lowest quartile, GDM risk in the highest quartile increased by 44% [odds ratio (OR) = 1.44; 95%CI, 1.08\u20131.92; <jats:italic>p<jats:sub>trend<\/jats:sub><\/jats:italic> = 0.027] for FT3 and 81% (OR = 1.81; 95%CI, 1.33\u20132.46; <jats:italic>p<jats:sub>trend<\/jats:sub><\/jats:italic> &amp;lt; 0.001) for FT3\/FT4, while it lowered by 37% (OR = 0.63; 95%CI, 0.47\u20130.86; <jats:italic>p<jats:sub>trend<\/jats:sub><\/jats:italic> = 0.002] for TSHI, 28% for TT4RI (OR = 0.72; 95%CI, 0.54\u20130.97; <jats:italic>p<jats:sub>trend<\/jats:sub><\/jats:italic> = 0.06), and 37% for TFQI (OR = 0.63; 95%CI, 0.46\u20130.85; <jats:italic>p<jats:sub>trend<\/jats:sub><\/jats:italic> &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This longitudinal study indicated that higher FT3 and FT3\/FT4 and lower central thyroid resistance indices were associated with increased risk of GDM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.806256","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T04:54:07Z","timestamp":1646715247000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Increased Central and Peripheral Thyroid Resistance Indices During the First Half of Gestation Were Associated With Lowered Risk of Gestational Diabetes\u2014Analyses Based on Huizhou Birth Cohort in South China"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhao-min","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Tao","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojie","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingtong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0457","article-title":"Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum","volume":"27","author":"Alexander","year":"2017","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2016.1269309","article-title":"Thyroid in Pregnancy: From Physiology to Screening","volume":"54","author":"Springer","year":"2017","journal-title":"Crit Rev Clin Lab Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0920","article-title":"Associations Between Human Chorionic Gonadotropin, Maternal Free Thyroxine, and Gestational Diabetes Mellitus","volume":"31","author":"Liu","year":"2021","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B4","article-title":"Thyroid Disease in Pregnancy","volume":"89","author":"Carney","year":"2014","journal-title":"Am Family Physician"},{"key":"B5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/bf03401381","article-title":"Thyroid Diseases During Pregnancy: A Number of Important Issues","volume":"14","author":"Krassas","year":"2015","journal-title":"Hormones (Athens Greece)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.7739","article-title":"Effects of Thyroid Diseases on Pregnancy Outcomes","volume":"18","author":"Zhou","year":"2019","journal-title":"Exp Ther Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1089\/thy.2005.15.899","article-title":"Peripheral Metabolism of Thyroid Hormone and Glucose Homeostasis","volume":"15","author":"Chidakel","year":"2005","journal-title":"Thyroid"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1315","article-title":"Dayan CM Clinical Review: A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range","volume":"98","author":"Taylor","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112183","article-title":"Gestational Diabetes Mellitus - A Metabolic and Reproductive Disorder","volume":"143","author":"Choudhury","year":"2021","journal-title":"Biomed Pharmacother = Biomed Pharmacother"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13008","article-title":"Influence of Different Diagnostic Criteria on Gestational Diabetes Mellitus Incidence and Medical Expenditures in China","volume":"10","author":"He","year":"2019","journal-title":"J Diabetes Invest"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.12751","article-title":"Meta-Analysis of the Association Between Maternal Subclinical Hypothyroidism and Gestational Diabetes Mellitus","volume":"144","author":"Jia","year":"2019","journal-title":"Int J Gynaecol Obstet: Off Organ Int Fed Gynaecol Obstet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4158\/ep13440.ra","article-title":"Maternal Subclinical Hypothyroidsm and Gestational Diabetes Mellitus: A Meta-Analysis","volume":"20","author":"Toulis","year":"2014","journal-title":"Endocrine Pract: Off J Am Coll Endocrinol Am Assoc Clin Endocrinologists"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02442","article-title":"Longitudinal Study of Thyroid Markers Across Pregnancy and the Risk of Gestational Diabetes","volume":"103","author":"Rawal","year":"2018","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1410","article-title":"Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome","volume":"42","author":"Laclaustra","year":"2019","journal-title":"Diabetes Care"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jcm9020359","article-title":"Central Resistance to Thyroid Hormones in Morbidly Obese Subjects Is Reversed After Bariatric Surgery-Induced Weight Loss","volume":"9","author":"Juiz-Vali\u00f1a","year":"2020","journal-title":"J Clin Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0215372","DOI":"10.1371\/journal.pone.0215372","article-title":"Risk Factors for Gestational Diabetes: An Umbrella Review of Meta-Analyses of Observational Studies","volume":"14","author":"Giannakou","year":"2019","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.657114","article-title":"Sensitivity to Thyroid Hormones and Risk of Prediabetes: A Cross-Sectional Study","volume":"12","author":"Liu","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1912185","article-title":"Vitamin D Supplementation and Prevention of Type 2 Diabetes","volume":"381","author":"Hassan-Smith","year":"2019","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03534.x","article-title":"The Use of Thyroid Function Tests in the Diagnosis of Hypopituitarism: Definition and Evaluation of the TSH Index","volume":"71","author":"Jostel","year":"2009","journal-title":"Clin Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2011.0087","article-title":"Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum","volume":"21","author":"Stagnaro-Green","year":"2011","journal-title":"Thyroid"},{"key":"B21","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1210\/er.2018-00163","article-title":"Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders","volume":"40","author":"Biondi","year":"2019","journal-title":"Endocrine Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1245","article-title":"And Obesity: An Intriguing Relationship","volume":"95","author":"Biondi. Thyroid","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114514002657","article-title":"Optimal Cut-Off Values of BMI, Waist Circumference and Waist:Height Ratio for Defining Obesity in Chinese Adults","volume":"112","author":"Zeng","year":"2014","journal-title":"Br J Nutr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0149065","DOI":"10.1371\/journal.pone.0149065","article-title":"First and C. Second Trimester Risk of Aneuploidy Research. Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes","volume":"11","author":"Haddow","year":"2016","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1530\/ec-21-0088","article-title":"The Role of Triiodothyronine (T3) and T3\/free Thyroxine (Ft4) in Glucose Metabolism During Pregnancy: The Ma\u2019anshan Birth Cohort Study","volume":"10","author":"Zhu","year":"2021","journal-title":"Endocrine Connect"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1530\/eje-15-0866","article-title":"Maternal Hypothyroxinaemia in Pregnancy is Associated With Obesity and Adverse Maternal Metabolic Parameters","volume":"174","author":"Knight","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02328","article-title":"Maternal BMI, Peripheral Deiodinase Activity, and Plasma Glucose: Relationships Between White Women in the HAPO Study","volume":"104","author":"Haddow","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318250aeeb","article-title":"Relationship of Subclinical Thyroid Disease to the Incidence of Gestational Diabetes","volume":"119","author":"Tudela","year":"2012","journal-title":"Obstet Gynecol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2540","article-title":"Thyroid Dysfunction and Autoantibodies in Early Pregnancy Are Associated With Increased Risk of Gestational Diabetes and Adverse Birth Outcomes","volume":"97","author":"Karakosta","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1530\/eje-07-0592","article-title":"Free Triiodothyronine Plasma Concentrations Are Positively Associated With Insulin Secretion in Euthyroid Individuals","volume":"158","author":"Ortega","year":"2008","journal-title":"Eur J Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02442","article-title":"A Longitudinal Study of Thyroid Markers Across Pregnancy and the Risk of Gestational Diabetes","volume":"103","author":"Rawal","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-1506","article-title":"Low Thyroid Hormone in Early Pregnancy Is Associated With an Increased Risk of Gestational Diabetes Mellitus","volume":"101","author":"Yang","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00136","article-title":"Is a Low Level of Free Thyroxine in the Maternal Circulation Associated With Altered Endothelial Function in Gestational Diabetes","volume":"5","author":"Guzm\u00e1n-Guti\u00e9rrez","year":"2014","journal-title":"Front Pharmacol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0011","article-title":"Increased Serum Adipocyte Fatty Acid-Binding Protein Levels Are Associated With Decreased Sensitivity to Thyroid Hormones in the Euthyroid Population","volume":"30","author":"Nie","year":"2020","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.S236698","article-title":"Associations Between Thyroid Hormones and Glycated Albumin in Euthyroid and Subclinical Hypothyroid Individuals: Results of an Observational Study","volume":"13","author":"Nie","year":"2020","journal-title":"Diabetes Metab Syndrome Obes: Targets Ther"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6663553","article-title":"Correlation Between Thyroid Homeostasis and Obesity in Subclinical Hypothyroidism: Community-Based Cross-Sectional Research","volume":"2021","author":"Zhou","year":"2021","journal-title":"Int J Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.931866","article-title":"Modulation of Type I Iodothyronine 5\u2019-Deiodinase Activity in White Adipose Tissue by Nutrition: Possible Involvement of Leptin","volume":"59","author":"Macek J\u00edlkov\u00e1","year":"2010","journal-title":"Physiol Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-121421","article-title":"Thyroid Function in Human Obesity: Underlying Mechanisms","volume":"48","author":"Fontenelle","year":"2016","journal-title":"Hormone Metab Res = Hormon- und Stoffwechselforschung = Hormones Metabolisme"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.12.056","article-title":"On Commonness and Rarity of Thyroid Hormone Resistance: A Discussion Based on Mechanisms of Reduced Sensitivity in Peripheral Tissues","volume":"69","author":"Tj\u00f8rve","year":"2007","journal-title":"Med Hypotheses"},{"key":"B40","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3109\/07435800.2012.699987","article-title":"Relationship of Thyroid Function With Obesity and Type 2 Diabetes in Euthyroid Tunisian Subjects","volume":"38","author":"Kouidhi","year":"2013","journal-title":"Endocrine Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0180","article-title":"Relationships Between Thyroid Function and Lipid Status or Insulin Resistance in a Pediatric Population","volume":"20","author":"Nader","year":"2010","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0557","article-title":"Variations in Serum Free Thyroxine Concentration Within the Reference Range Predicts the Incidence of Metabolic Syndrome in Non-Obese Adults: A Cohort Study","volume":"27","author":"Mehran","year":"2017","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2013.10.003","article-title":"Pitfalls in the Measurement and Interpretation of Thyroid Function Tests","volume":"27","author":"Koulouri","year":"2013","journal-title":"Best Pract Res Clin Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.806256\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T04:54:11Z","timestamp":1646715251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.806256\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":43,"alternative-id":["10.3389\/fendo.2022.806256"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.806256","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]},"article-number":"806256"}}