Download PDF
Horm Metab Res 2023; 55(04): 245-250
DOI: 10.1055/a-2003-0211
Original Article: Endocrine Care

Isolated Maternal Hypothyroxinemia May be Associated with Insulin Requirement in Gestational Diabetes Mellitus

Ömercan Topaloğlu 
1   Endocrinology, Zonguldak Bülent Ecevit University Faculty of Medicine, Zonguldak, Turkey
,
Mehmet Uzun
2   Oncology, Dokuz Eylül Üniversitesi Tıp Fakültesi, Izmir, Turkey
,
Seda Nur Topaloğlu
3   Internal Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Turkey
,
Ibrahim Sahin
4   Endocrinology, İnönü Üniversitesi Tıp Fakültesi, Malatya, Turkey
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

An insulin regimen may be necessary for about 30% of the patients with gestational diabetes mellitus (GDM). We aimed to investigate the association of free T4(fT4) levels with insulin requirement in pregnant women with GDM. We included pregnant women whose TSH levels were within the normal range and who were diagnosed with GDM, and excluded patients with thyroid dysfunction, chronic illnesses, or any previous history of antithyroid medication, levothyroxine, or antidiabetic medication use. The diagnosis and treatment of GDM were based on American Diabetes Association guidelines. Demographic features, previous history of GDM and gestational hypertension were recorded. Baseline (at diagnosis of GDM) fasting blood glucose, HbA1c, TSH, fT4, and fT3 levels were analyzed. We grouped the patients according to their baseline fT4 levels: isolated maternal hypothyroxinemia (IMH) (group A) vs. in the normal range (group B). We grouped those also based on insulin requirement in 3rd trimester. Of the patients (n=223), insulin requirement was present in 56, and IMH in 11. Insulin requirement was more frequent in group A than in group B (p=0,003). HbA1c (≥47,5 mmol/mol) and fT4 level (lower than normal range) were positive predictors for insulin requirement (OR:35,35, p=0,001; and OR:6,05, p=0,008; respectively). We showed that IMH was closely associated with insulin requirement in GDM. Pregnant women with IMH and GDM should be closely observed as regards to glycemic control. If supported by future large studies, levothyroxine treatment might be questioned as an indication for patients with GDM and IMH.

Key words

diabetes - gestational - thyroid - hypothyroxinemia - insulin - isolated


Publication History

Received: 02 November 2022

Accepted after revision: 21 December 2022

Accepted Manuscript online:
21 December 2022

Article published online:
10 February 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, Bakris G et al. 15. Management of diabetes in pregnancy: standards of medical care in diabetes-2022. Diabetes Care 2022; 45 : S232–S243
    PubMed
  • 2 Mayo K, Melamed N, Vandenberghe H. et al. The impact of adoption of the international association of diabetes in pregnancy study group criteria for the screening and diagnosis of gestational diabetes. Am J Obstet Gynecol 2015; 212: e1-e9
    CrossrefPubMedGoogle Scholar
  • 3 Dash P, Tiwari R, Nayak S. et al. Prevalence of subclinical hypothyroidism in pregnancy and its association with anti-thyroperoxidase antibody and the occurrence of gestational diabetes mellitus. Cureus 2022; 14: e21087
    PubMedGoogle Scholar
  • 4 Wang J, Gong XH, Peng T. et al. Association of thyroid function during pregnancy with the risk of pre-eclampsia and gestational diabetes mellitus. Endocr Pract 2021; 27: 819-825
    CrossrefPubMedGoogle Scholar
  • 5 Li P, Lin S, Cui J. et al. Impact of early pregnancy subclinical hypothyroidism on gestational diabetes mellitus: a retrospective study of 7,536 Cases. J Womens Health (Larchmt) 2022; 31: 293-298
    CrossrefPubMedGoogle Scholar
  • 6 Luo J, Wang X, Yuan L. et al. Association of thyroid disorders with gestational diabetes mellitus: a meta-analysis. Endocrine 2021; 73: 550-560
    CrossrefPubMedGoogle Scholar
  • 7 Zhu P, Chu R, Pan S. et al. Impact of TPOAb-negative maternal subclinical hypothyroidism in early pregnancy on adverse pregnancy outcomes. Ther Adv Endocrinol Metab 2021; 12 20420188211054690
    PubMedGoogle Scholar
  • 8 Ramezani Tehrani F, Nazarpour S, Behboudi-Gandevani S. Isolated maternal hypothyroxinemia and adverse pregnancy outcomes: a systematic review. J Gynecol Obstet Hum Reprod 2021; 50: 102057
    CrossrefPubMedGoogle Scholar
  • 9 Li G, Liu Y, Su X. et al. Effect of levothyroxine on pregnancy outcomes in pregnant women with hypothyroxinemia: an interventional study. Front Endocrinol (Lausanne) 2022; 13: 874975
    CrossrefPubMedGoogle Scholar
  • 10 American Diabetes Association Professional Practice Committee 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care 2022; 45: S17-S38
    CrossrefPubMedGoogle Scholar
  • 11 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. Erratum in: Thyroid 2017; 27: 1212
    PubMedGoogle Scholar
  • 12 Chen L, Yang H, Ye E. et al. Insignificant effect of isolated hypothyroxinemia on pregnancy outcomes during the first and second trimester of pregnancy. Front Endocrinol (Lausanne) 2020; 11: 528146
    CrossrefPubMedGoogle Scholar
  • 13 Morreale de Escobar G, Obregón MJ, Escobar del Rey F. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia?. J Clin Endocrinol Metab 2000; 85: 3975-3987
    PubMedGoogle Scholar
  • 14 Casey BM, Dashe JS, Spong CY. et al. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol 2007; 109: 1129-1135
    CrossrefPubMedGoogle Scholar
  • 15 Pop VJ, Brouwers EP, Vader HL. et al. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol (Oxf) 2003; 59: 282-288
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 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 Endocrinol Metab 2016; 101: 4237-4243
    CrossrefPubMedGoogle Scholar
  • 18 Gong X, Liu A, Li Y. et al. The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China. J Endocrinol Invest 2019; 42: 599-607
    CrossrefPubMedGoogle Scholar
  • 19 Su X, Zhao Y, Cao Z. et al. Association between isolated hypothyroxinaemia in early pregnancy and perinatal outcomes. Endocr Connect 2019; 8: 435-441
    CrossrefPubMedGoogle Scholar
  • 20 Rosario PW, Oliveira LFF, Calsolari MR. Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study. Arch Endocrinol Metab 2018; 62: 332-336
    PubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Eom YS, Wilson JR, Bernet VJ. Links between thyroid disorders and glucose homeostasis. Diabetes Metab J 2022; 46: 239-256
    CrossrefPubMedGoogle Scholar
  • 23 Aguayo-Mazzucato C, Zavacki AM, Marinelarena A. et al. Thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through MAFA. Diabetes 2013; 62: 1569-1580
    CrossrefPubMedGoogle Scholar
  • 24 Verga Falzacappa C, Mangialardo C, Madaro L. et al. Thyroid hormone T3 counteracts STZ induced diabetes in mouse. PLoS One 2011; 6: e19839
    CrossrefPubMedGoogle Scholar
  • 25 Nishi M. Diabetes mellitus and thyroid diseases. Diabetol Int 2018; 9: 108-112
    CrossrefPubMedGoogle Scholar
  • 26 Klieverik LP, Janssen SF, van Riel A. et al. Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. Proc Natl Acad Sci U S A 2009; 106: 5966-5971
    CrossrefPubMedGoogle Scholar
  • 27 Rawal S, Tsai MY, Hinkle SN. et al. A longitudinal study of thyroid markers across pregnancy and the risk of gestational diabetes. J Clin Endocrinol Metab 2018; 103: 2447-2456
    CrossrefPubMedGoogle Scholar
  • 28 Toulis KA, Stagnaro-Green A, Negro R. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta-analysis. Endocr Pract 2014; 20: 703-714
    CrossrefPubMedGoogle Scholar
  • 29 Al-Attas OS, Al-Daghri NM, Alkharfy KM. et al. Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes 2012; 120: 618-622
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 Silva de Morais N, Ayres Saraiva D, Corcino C. et al. Consequences of iodine deficiency and excess in pregnancy and neonatal outcomes: a prospective cohort study in Rio de Janeiro, Brazil. Thyroid 2020; 30: 1792-1801
    CrossrefPubMedGoogle Scholar
  • 32 Ford HL, Champion I, Wan A. et al. Predictors for insulin use in gestational diabetes mellitus. Eur J Obstet Gynecol Reprod Biol 2022; 272: 177-1781
    CrossrefPubMedGoogle Scholar
  • 33 Alvarez-Silvares E, Bermúdez-González M, Vilouta-Romero M. et al. Prediction of insulin therapy in women with gestational diabetes: a systematic review and meta-analysis of observational studies. J Perinat Med 2022; 50: 608-619
    CrossrefPubMedGoogle Scholar
  • 34 Wang T, Yin W, Huang Y. et al. Identification of significant predictors for the need of insulin therapy and onset of postpartum impaired glucose tolerance in gestational diabetes mellitus patients. Diabetes Metab Syndr Obes 2021; 14: 2609-2617
    CrossrefPubMedGoogle Scholar
  • 35 Akgöl S, Budak MŞ, Oğlak SC. et al. Can maternal abdominal fat thickness predict antenatal insulin therapy in patients with gestational diabetes mellitus?. J Obstet Gynaecol Res 2022; 48: 634-639
    CrossrefPubMedGoogle Scholar
  • 36 Hijikata M, Higa M, Ichijo T. et al. A comparison of meal tolerance test and oral glucose tolerance test for predicting insulin therapy in patients with gestational diabetes. Food Nutr Res 2021; 65 10.29219
    PubMedGoogle Scholar
  • 37 Ying H, Tang YP, Bao YR. et al. Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus. Endocrine 2016; 54: 742-750
    CrossrefPubMedGoogle Scholar
  • 38 Chen LM, Zhang Q, Si GX. et al. Associations between thyroid autoantibody status and abnormal pregnancy outcomes in euthyroid women. Endocrine 2015; 48: 924-928
    CrossrefPubMedGoogle Scholar
  • 39 Chen GD, Gou XY, Pang TT. et al. Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study. BMC Endocr Disord 2022; 22: 44
    CrossrefPubMedGoogle Scholar
  • 40 Demiral Sezer S, Topaloglu O. Effects of thyroid hormones in women with gestational diabetes. Gynecol Endocrinol 2022; 38: 588-591
    CrossrefPubMedGoogle Scholar