The Relationship Between Subclinical Hypothyroidism and Gestational Diabetes Mellitus

Abstract

Aim: The most common metabolic disorder during pregnancy is gestational diabetes mellitus (GDM). GDM can occur in anywhere between 1.7 and 11.6 percent of people. In hypothyroidism, the rates of glucose oxidation and glycogen synthesis are reduced, and the peripheral tissues' consumption of glucose is also delayed. Patients with subclinical and overt hypothyroidism develop insulin resistance because insulin is unable to adequately maintain the muscles' use of glucose. According to the literature, hypothyroidism is linked to 6–15 percent of GDM pregnancies. Additionally, the chance of having GDM is 4.3 times higher in pregnant women who have hypothyroidism. This study aimed to reveal the relationship between first-trimester thyroid function tests and GDM. Material and Method: This retrospective cohort study was conducted between May 2021 and May 2022. 100 pregnant patients diagnosed with GDM and 500 healthy controls were included in the study. Using a 75 g glucose challenge test, GDM was identified. The trimester-specific recognized normal limits were used to evaluate the TSH and fT4 readings. Results: There was a statistically significant difference in terms of SCH between patients with and without GDM (p=0.04). TSH's performance in predicting GDM was evaluated using AUC and ROC (AUC=0.586 and p=0.006). To forecast GDM, the TSH level cut-off value was discovered to be 1.58. The AUC was found to be 0.586 (0.521-0.652). Furthermore, the selectivity is 58% and the sensitivity is 41% Conclusion: There are many studies in the literature investigating thyroid functions and the development of gestational diabetes mellitus. Our study also found a correlation between the diagnosis of subclinical hypothyroidism in the first trimester and GDM. The study adds to the literature the importance of being cautious and vigilant in terms of the development of gestational diabetes mellitus based on the results of the thyroid function test in the first trimester.

Keywords

• Gestational Diabetes Mellitus
• Hypothyroidism
• Pregnancy

Subklinik Hipotiroidizm ile Gestasyonel Diabetes Mellitus Arasındaki İlişki

Abstract

Amaç: Gebelikte en sık görülen metabolik bozukluk gestasyonel diyabetes mellitustur (GDM). GDM prevalansı yüzde 1,7 ile yüzde 11,6 arasında değişmektedir. Hipotiroidizmde glukoz oksidasyonu ve glikojen sentezi hızları azalır ve periferik dokularda glukoz kullanımı yavaşlar. Subklinik ve aşikar hipotiroidili hastalarda insülin direnci gelişir çünkü insülin kasların glikoz kullanımını yeterince sürdüremez. Literatüre göre, hipotiroidizm GDM gebeliklerinin yüzde 6-15'i ile bağlantılıdır. Ayrıca hipotiroidisi olan gebelerde GDM olma olasılığı 4,3 kat daha fazladır. Bu çalışma birinci trimester tiroid fonksiyon testleri ile GDM arasındaki ilişkiyi ortaya koymayı amaçlamıştır. Gereç ve Yöntem: Bu retrospektif kohort çalışma Mayıs 2021 ile Mayıs 2022 tarihleri ​​arasında yapıldı. Çalışmaya GDM tanısı konan 100 gebe hasta ve 500 sağlıklı kontrol dahil edildi. GDM, 75 g glikoz yükleme testi kullanılarak teşhis edildi. TSH ve sT4 değerleri trimestere göre kabul edilen normal sınırlara göre değerlendirildi. Bulgular: GDM olan ve olmayan hastalar arasında SKH açısından istatistiksel olarak anlamlı fark vardı (p=0.04). AUC ve ROC, TSH'nin GDM'yi öngörme performansını değerlendirmek için kullanıldı (AUC=0.586 ve p=0.006). GDM'yi öngörmek için TSH düzeyi cut-off değeri 1.58 olarak belirlendi. AUC'nin 0,586 (0,521-0,652) olduğu bulundu. Ayrıca seçicilik %58 ve duyarlılık %41'dir. Sonuç: Literatürde tiroid fonksiyonlarını ve gestasyonel diabetes mellitus gelişimini araştıran birçok çalışma bulunmaktadır. Bizim çalışmamızda da birinci trimesterde subklinik hipotiroidi tanısı ile GDM arasında ilişki bulundu. Çalışma, birinci trimester tiroid fonksiyon testi sonuçlarına dayanarak, gestasyonel diyabetes mellitus gelişimi açısından dikkatli ve uyanık olmanın önemini literatüre katmaktadır.

Keywords

• Gestasyonel Diabetes Mellitus
• Hipotiroidizm
• Gebelik

References

1. World Health Organization. Laboratory diagnosis and monitoring of diabetes mellitus. 2003
2. Schneider S, Bock C, Wetzel M, Maul H, Loerbrock A. The prevalence of gestational diabetes in advanced economies. J Perinatal Med 2012. http://dx.doi.org/10.1515/jpm-2012-0015
3. Poston L. Developmental programming and diabetes – the human experience and insight from animal models. Best Pract Res Clin Endocrinol Metab 2010;24:541-52.
4. Negrato CA, Montenegro Junior RM, Von Kostrisch LM, Guedes MF, Mattar R, Gomes MB. Insulin analogues in the treatment of diabetes in pregnancy. Arq Bras Endocrinol Metabol 2012;56(7):405-414.
5. Velkoska Nakova V, Krstevska B, Dimitrovski Ch, Simeonova S, Hadzi-Lega M, Serafimoski V. Prevalence of thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes and diabetes type 1. Prilozi. 2010;31(2):51-59.
6. Olivieri A, Valensise H, Magnani F, et al. High frequency of antithyroid autoantibodies in pregnant women at increased risk of gestational diabetes mellitus. Eur J Endocrinol. 2000;143(6):741-7.
7. Okajima F, Ui M. Metabolism of glucose in hyperand hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3 H-labelled glucose. Biochem J. 1979;182(2): 565–75.
8. Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. New Engl J Med 1999;341:549–55.

9. Liu X, Andersen SL, Olsen J, Agerbo E, et al. Maternal hypothyroidism in the perinatal period and childhood asthma in the offspring. Allergy 2018;73:932–9.
10. Derakhshan A, Korevaar TIM, Taylor PN, et al. The Association of Maternal Thyroid Autoimmunity during pregnancy with child IQ. J Clin Endocrinol Metab 2018;103:3729–36.
11. Thorpe-Beeston JG, Nicolaides KH, Felton CV, Butler J, McGregor AM. Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus. New Engl J Med 1991;324:532–6.
12. Obregon MJ, Calvo RM, Del Rey FE, de Escobar GM. Ontogenesis of thyroid function and interactions with maternal function. Endocr Develop 2007;10:86–98.
13. Gutiérrez-Vega S, Armella A, Mennickent D, et al. High levels of maternal total tri-iodothyronine, and low levels of fetal free L-thyroxine and total tri-iodothyronine, are associated with altered deiodinase expression and activity in placenta with gestational diabetes mellitus. Plos One. 2020;15(11):e0242743.
14. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012;119(5):983-8.
15. Stohl HE, Ouzounian J, Rick AM, Hueppchen NA, Bienstock JL. Thyroid disease and gestational diabetes mellitus (GDM): is there a connection?. J Matern Fetal Neonatal Med 2013;26(11):1139-42.
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 Endocrinol Metab. 2012;97(12):4464-72.
17. Hage M, Zantout MS, Azar ST. Thyroid disorders and diabetes mellitus. J Thyroid Res. 2011;2011:439463.
18. Ashoor G, Kametas NA, Akolekar R, Guisado J, Nicolaides KH. Maternal thyroid function at 11–13 weeks of gestation. Fetal Diagn Ther. 2010; 27(3):156–63.
19. Mannisto T, Surcel HM, Ruokonen A, et al. Early pregnancy refer ence intervals of thyroid hormone concentrations in a thyroid antibody-negative pregnant population.Thyroid. 2011; 21(3):291–8.
20. Bestwick JP, John R, Maina A, et al. Thyroid stimulating hormone and free thyroxine in pregnancy: expressing concentrations as multiples of the median (MoMs). Clin Chim Acta. 2014; 430:33–7.
21. Haddow JE, Craig WY, Neveux LM, et al. Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes. PLoS One. 2016;11(2):e0149065.
22. Biondi B, Kahaly GJ, Robertson RP. Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders. Endocr Rev. 2019;40(3):789-824.
23. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol. 2012;119(5):983–8.
24. Zhang Y, Dai X, Yang S, Zhang C, Han M, Huang HF, Fan J. Maternal low thyroxin levels are associated with adverse pregnancy outcomes in a Chinese population. PLoS One. 2017;12(5):e0178100.
25. 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):4237–43.
26. Safian S, Esna-Ashari F, Borzouei S. Thyroid dysfunction in pregnant women with gestational diabetes mellitus. Curr Diabetes Rev 2020;16(8):895-9.
27. Wang J, Gong XH, Peng T, Wu JN. Association of Thyroid Function During Pregnancy With the Risk of Pre-eclampsia and Gestational Diabetes Mellitus. Endocr Pract. 2021;27(8):819-25.
28. Luo J, Wang X, Yuan L, Guo L. Association of thyroid disorders with gestational diabetes mellitus: a meta-analysis. Endocrine 2021;73(3):550-60.
29. 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):261-6.
30. 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(1):44.