بررسی مقایسه‌ای دیابت بارداری در زنان مبتلا به هیپوتیروئیدی تحت بالینی تیروئید با زنان یوتیروئید

نوع مقاله : اصیل پژوهشی

نویسندگان

1 استادیار گروه مامایی، دانشکده پزشکی، دانشگاه آزاد اسلامی، واحد ورامین- پیشوا، تهران، ایران. محقق پسادکترای مرکز تحقیقات اندوکرینولوژی تولید مثل، پژوهشکده علوم غدد درون‌ریز و متابولیسم‌، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

2 استاد مرکز تحقیقات اندوکرینولوژی تولید مثل، پژوهشکده علوم غدد درون‌ریز و متابولیسم، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

3 دکترای آمار زیستی، مرکز تحقیقات اندوکرینولوژی تولید مثل، پژوهشکده علوم غدد درون‌ریز و متابولیسم، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

4 استاد مرکز تحقیقات غدد درون‌ریز، پژوهشکده علوم غدد درون‌ریز و متابولیسم، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

چکیده

مقدمه: ارتباط بین هیپوتیروئیدی تحت بالینی (SCH) و دیابت بارداری (GDM) موضوع بحث‌برانگیزی است. مطالعه حاضر با هدف مقایسه دیابت بارداری در زنان مبتلا به هیپوتیروئیدی تحت بالینی با زنان یوتیروئید انجام شد.
روشکار: در این مطالعه آینده‌نگر، از داده‌های به‌دست آمده از ۱۰۲۶ زن باردار (شامل ۶۸۳ یوتیروئید و ۳۴۳ زن مبتلا به SCH) در مطالعه کوهورت تیروئید و بارداری تهران استفاده شد. سطح سرمی تیروتروپین (TSH)، تیروکسین (T4)، T3-uptake و آنتی‌بادی پراکسیداز تیروئید (TPOAb) در اولین ویزیت سه ماهه اول بارداری مورد بررسی قرار گرفت و بر این اساس، زنان یوتیروئید و مبتلا به هیپوتیروئیدی تحت بالینی مشخص گردیدند. این دو گروه از نظر دیابت بارداری مورد مطالعه قرار گرفتند. تجزیه و تحلیل داده‌ها با استفاده از نرم‌افزار STATA (نسخه 13) انجام شد. متغیرهای پیوسته با استفاده از آزمون تی مستقل و من‌ویتنی و متغیرهای رسته‌ای  با استفاده از آزمون کی‌ دو یا آزمون دقیق فیشر بین دو گروه مقایسه شدند. به‌منظور شناسایی اثر SCH و مصرف لووتیروکسین بر GDM از مدل لگ باینومیال استفاده گردید میزان p کمتر از 05/0 معنی‌دار در نظر گرفته شد.
یافته‌ها: تفاوت معنی‌داری در دیابت بارداری در افراد مبتلا به هیپوتیروئیدی تحت بالینی در مقایسه با گروه کنترل چه در مدل تعدیل نشده و چه بعد از تعدیل اثر ریسک فاکتورها مشاهده نشد. همچنین تفاوت معنی‌داری در دیابت بارداری بین گروه هیپوتیروئیدی تحت بالینی باTPOAb+ ، گروه هیپوتیروئیدی تحت بالینی با TPOAb- و افراد یوتیروئید وجود نداشت. ریسک دیابت بارداری در گروه TPOAb+ تفاوت معنی‌داری با ریسک دیابت بارداری در گروه TPOAb+ منفی نداشت. سطح سرمی TSH (9/0=p)، T4 (8/0=p)، T3-uptake (7/0=p) و TPOAb (4/0=p) نیز در دو گروه مبتلا و غیرمبتلا به دیابت بارداری تفاوت معنی‌داری نداشتند.
نتیجه‌گیری: اگرچه در این مطالعه ارتباط معنی‌داری بین دیابت بارداری و هیپوتیروئیدی تحت بالینی مشاهده نشد، اما به‌نظر می‌رسد با توجه به عوامل مختلف مؤثر بر بروز هیپوتیروئیدی تحت بالینی و دیابت بارداری از جمله معیارهای تشخیصی و مقادیر مرجع مختلف، اثبات این موضوع نیازمند مطالعات بیشتری است.

کلیدواژه‌ها


عنوان مقاله [English]

Gestational diabetes incidence in women with subclinical hypothyroidism and euthyroid women

نویسندگان [English]

  • Sima Nazarpour 1
  • Fahimeh Ramezani Tehrani 2
  • Maryam Rahmati 3
  • Fereidoun Azizi 4
1 Assistant Professor, Department of Midwifery, Faculty of Medicine, Varamin-Pishva Branch, Islamic Azad University, Tehran, Iran. Postdoctorate Researcher, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2 Professor, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 Ph.D. of Biostatistics, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Professor, Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
چکیده [English]

Introduction: The association between subclinical hypothyroidism (SCH) and gestational diabetes (GDM) is controversial. This study was performed with aim to compare the incidence of GDM in women with SCH and euthyroid women.
Methods: In this prospective study, data obtained from 1026 pregnant women (including 683 cases of euthyroid and 343 women with SCH) participating in the cohort study of Tehran thyroid and pregnancy (TTP) was used. Serum levels of thyrotropin (TSH), thyroxine (T4), T3-uptake, and thyroid peroxidase antibody (TPOAb) were measured at first visit of the first trimester of pregnancy; based on this, euthyroid and SCH women were identified. These two groups were evaluated for gestational diabetes. Data were analyzed using STATA software (version 13). The continuous variables were compared between the two groups using independent t-test and Mann-Whitney test, and categorical variables using chi-square test or Fisher's exact test. Log-binomial model was used to identify the effect of SCH and levothyroxine on GDM. P< 0.05 was considered statistically significant
Results: There was no significant difference in the incidence of GDM in SCH women compared to the control group either in the unadjusted model or after adjusting for the effective risk factors. Also, there was no significant difference in the incidence of GDM between SCH with TPOAb+, SCH with TPOAb-, and euthyroid groups. The risk of GDM in the TPOAb positive group was not significantly different from TPOAb negative group. Serum TSH (p=0.9), T4 (p=0.8), T3-uptake (p=0.7), and TPOAb (p=0.4) levels were not significantly different between the GDM and non-GDM groups.
Conclusion: Although no significant association was found between GDM and SCH in this study, however, it seems that due to various factors affecting the incidence of SCH and GDM, such as different diagnostic criteria and reference values, proving this issue requires further studies.

کلیدواژه‌ها [English]

  • Gestational diabetes
  • Hypothyroidism
  • Insulin resistance
  • Pregnancy
  • Thyroid
  1. Nazarpour S, Ramezani Tehrani F, Simbar M, Azizi F. Pregnancy outcomes in pregnant women with hypothyroidism (A review Article). Iran J Obstet Gynecol Infertil 2014; 17(126):17-26.
  2. Lotfalizadeh M, Ghomian N, Mohammad Nezhad M. Prevalence and complications of hypothyroidism in pregnancy. Iran J Obstet Gynecol Infertil 2017; 20(8):1-5.
  3. Cooper DS, Biondi B. Subclinical thyroid disease. The Lancet 2012; 379(9821):1142-54.
  4. Negro R, Stagnaro-Green A. Diagnosis and management of subclinical hypothyroidism in pregnancy. Bmj 2014; 349.
  5. Poppe K, Bisschop P, Fugazzola L, Minziori G, Unuane D, Weghofer A. 2021 European thyroid association guideline on thyroid disorders prior to and during assisted reproduction. European thyroid journal 2021; 9(6):281-95.
  6. Yadav V, Dabar D, Goel AD, Bairwa M, Sood A, Prasad P, Agarwal SS, Nandeshwar S. Prevalence of hypothyroidism in pregnant women in India: a meta-analysis of observational studies. Journal of thyroid research 2021; 2021.
  7. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002; 12(1):63-8.
  8. Nazarpour S, Tehrani FR, Simbar M, Azizi F. Thyroid dysfunction and pregnancy outcomes. Iranian journal of reproductive medicine 2015; 13(7):387.
  9. Batistuzzo A, Ribeiro MO. Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition. Archives of endocrinology and metabolism 2020; 64:89-95.
  10. Wendland EM, Torloni MR, Falavigna M, Trujillo J, Dode MA, Campos MA, et al. Gestational diabetes and pregnancy outcomes-a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria. BMC pregnancy and childbirth 2012; 12(1):1-3.
  11. Wang C. The relationship between type 2 diabetes mellitus and related thyroid diseases. Journal of diabetes research 2013; 2013.
  12. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes care 2004; 27(5):1047-53.
  13. Maraka S, Mwangi R, McCoy RG, Yao X, Sangaralingham LR, Ospina NM, et al. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. Bmj 2017; 356.
  14. Distiller LA, Polakow ES, Joffe BI. Type 2 diabetes mellitus and hypothyroidism: the possible influence of metformin therapy. Diabetic Medicine 2014; 31(2):172-5.
  15. Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Alavi Majd H, Azizi F. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur J Endocrinol 2017; 176(2):253-65.
  16. Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Minooee S, Rahmati M, et al. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. The Journal of Clinical Endocrinology & Metabolism 2018; 103(3):926-35.
  17. van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, et al. Significance of (sub) clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Human reproduction update 2011; 17(5):605-19.
  18. American College of Obstetrics and Gynecology. ACOG practice bulletin. Thyroid disease in pregnancy. Number 37, August 2002. American College of Obstetrics and Gynecology. Int J Gynaecol Obstet 2002; 79(2):171-80.
  19. Shahbazian H, Nouhjah S, Shahbazian N, Jahanfar S, Latifi SM, Aleali A, et al. Gestational diabetes mellitus in an Iranian pregnant population using IADPSG criteria: incidence, contributing factors and outcomes. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 2016; 10(4):242-6.
  20. Hage M, Zantout MS, Azar ST. Thyroid disorders and diabetes mellitus. Journal of thyroid research 2011; 2011:439463.
  21. Stohl HE, Ouzounian J, Rick AM, Hueppchen NA, Bienstock JL. Thyroid disease and gestational diabetes mellitus (GDM): is there a connection?. The Journal of Maternal-Fetal & Neonatal Medicine 2013; 26(11):1139-42.
  22. de Jesus Garduno-Garcia J, Alvirde-Garcia U, Lopez-Carrasco G, Mendoza ME, Mehta R, Arellano-Campos O, et al. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol 2010; 163:273-8.
  23. Dimitriadis G, Mitrou P, Lambadiari V, Boutati E, Maratou E, Panagiotakos DB, et al. Insulin action in adipose tissue and muscle in hypothyroidism. The Journal of Clinical Endocrinology & Metabolism 2006; 91(12):4930-7.
  24. Maratou E, Hadjidakis DJ, Peppa M, Alevizaki M, Tsegka K, Lambadiari V, et al. Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism. European journal of endocrinology 2010; 163(4):625.
  25. Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. The Journal of Clinical Endocrinology & Metabolism 2007; 92(2):491-6.
  26. Chubb SA, Davis WA, Inman Z, Davis TM. Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study. Clinical endocrinology 2005; 62(4):480-6.
  27. Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabetic medicine 1995; 12(7):622-7.
  28. Fister P, Gaberšček S, Zaletel K, Krhin B, Geršak K, Hojker S. Thyroid volume changes during pregnancy and after delivery in an iodine-sufficient Republic of Slovenia. European Journal of Obstetrics & Gynecology and Reproductive Biology 2009; 145(1):45-8.
  29. Lazarus JH. Thyroid function in pregnancy. Br Med Bull 2011; 97:137-48.
  30. Toulis KA, Stagnaro-Green A, Negro R. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta-analysis. Endocrine practice 2014; 20(7):703-14.
  31. 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. Archives of gynecology and obstetrics 2010; 281(2):215-20.
  32. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstetrics & Gynecology 2012; 119(5):983-8.
  33. Ying H, Tang YP, Bao YR, Su XJ, Cai X, Li YH, et al. Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus. Endocrine 2016; 54(3):742-50.
  34. Chen LM, Du WJ, Dai J, Zhang Q, Si GX, Yang H, 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(10):e109364.
  35. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, et al. Maternal thyroid hypofunction and pregnancy outcome. Obstetrics and gynecology 2008; 112(1):85.
  36. Mannisto T, Vaarasmaki M, Pouta A, Hartikainen AL, Ruokonen A, Surcel HM, et al. Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life. The Journal of Clinical Endocrinology & Metabolism 2010; 95(3):1084-94.
  37. 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. Gynecological Endocrinology 2006; 22(5):261-6.
  38. Muir CA, Munsif A, Blaker K, Feng Y, D’souza M, Tewari S. Antenatal Thyroid Function Does Not Increase Risk of Gestational Diabetes Mellitus in a Multi-Ethnic Pregnancy Cohort. Internationa Journal of Thyroidology 2020; 13(1):13-8.
  39. Nazarpour S, Tehrani FR, Simbar M, Tohidi M, Azizi F. Thyroid and pregnancy in Tehran, Iran: objectives and study protocol. International journal of endocrinology and metabolism 2016; 14(1):e33477.
  40. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21(10):1081-125.
  41. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes care 2010; 33(3):676-82.
  42. Chubb SA, Davis WA, Davis TM. Interactions among thyroid function, insulin sensitivity, and serum lipid concentrations: the Fremantle diabetes study. The Journal of Clinical Endocrinology & Metabolism 2005; 90(9):5317-20.
  43. Calina D, Docea AO, Golokhvast KS, Sifakis S, Tsatsakis A, Makrigiannakis A. Management of endocrinopathies in pregnancy: a review of current evidence. International journal of environmental research and public health 2019; 16(5):781.
  44. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37 Suppl 1:S81-90.
  45. Karakosta P, Alegakis D, Georgiou V, Roumeliotaki T, Fthenou E, Vassilaki M, et al. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. The Journal of Clinical Endocrinology & Metabolism 2012; 97(12):4464-72.
  46. Das DK, Bandyopadhyay D, Bandyopadhyay S, Neogi A. Thyroid hormone regulation of β-adrenergic receptors and catecholamine sensitive adenylate cyclase in foetal heart. European Journal of Endocrinology 1984; 106(4):569-76.
  47. Oguz A, Tuzun D, Sahin M, Usluogullari AC, Usluogullari B, Celik A, et al. Frequency of isolated maternal hypothyroxinemia in women with gestational diabetes mellitus in a moderately iodine-deficient area. Gynecological Endocrinology 2015; 31(10):792-5.
  48. YuanI P, Wang Q, Huang R, Cao F, Zhu Z, Sun D, et al. Clinical evaluation with self-sequential longitudinal reference intervals: pregnancy outcome and neonatal thyroid stimulating hormone level associated with maternal thyroid diseases. West Indian Med J 2013: 28-34.
  49. Amouzegar A, Mehran L, Takyar M, Abdi H, Azizi F. Tehran thyroid study (TTS). International journal of endocrinology and metabolism 2018; 16(4 Suppl).
  50. Zimmermann MB. Iodine deficiency. Endocrine reviews 2009; 30(4):376-408.
  51. Blatt AJ, Nakamoto JM, Kaufman HW. National status of testing for hypothyroidism during pregnancy and postpartum. The Journal of Clinical Endocrinology & Metabolism 2012; 97(3):777-84.
  52. Sharifi F, Nezamdiba M, Kamali K. Thyroid function and its relation to insulin resistance in women with gestational diabetes mellitus (GDM) compared with healthy pregnant women. J Adv Med Biomed Res 2014; 22(94):61-71.
  53. Arbib N, Hadar E, Sneh-Arbib O, Chen R, Wiznitzer A, Gabbay-Benziv R. First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome. The Journal of Maternal-Fetal & Neonatal Medicine 2017; 30(18):2174-8.
  54. Huang K, Xu Y, Yan S, Li T, Xu Y, Zhu P, 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. Endocrine journal 2019: EJ18-0340.
  55. Al-Shoumer KA, Vasanthy BA, Al-Zaid MM. Effects of treatment of hyperthyroidism on glucose homeostasis, insulin secretion, and markers of bone turnover. Endocrine Practice 2006; 12(2):121-30.
  56. Bilic-Komarica E, Beciragic A, Junuzovic D. Effects of treatment with L-thyroxin on glucose regulation in patients with subclinical hypothyroidism. Med Arh 2012; 66(66):364-8.
  57. Deetman PE, Bakker SJ, Kwakernaak AJ, Navis G, Dullaart RP, PREVEND Study Group. The relationship of the anti-oxidant bilirubin with free thyroxine is modified by insulin resistance in euthyroid subjects. PloS one 2014; 9(3):e90886.
  58. Rochon C, Tauveron I, Dejax C, Benoit P, Capitan P, Fabricio A, et al. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clinical science 2003; 104(1):7-15.
  59. Ortega-González C, Liao-Lo A, Ramírez-Peredo J, Cariño N, Lira J, Parra A. Thyroid peroxidase antibodies in Mexican-born healthy pregnant women, in women with type 2 or gestational diabetes mellitus, and in their offspring. Endocrine Practice 2000; 6(3):244-8.
  60. Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends in Endocrinology & Metabolism 2014; 25(3):138-45.
  61. Kapadia KB, Bhatt PA, Shah JS. Association between altered thyroid state and insulin resistance. Journal of pharmacology & pharmacotherapeutics 2012; 3(2):156.
  62. Prummel MF, Wiersinga WM. Thyroid peroxidase autoantibodies in euthyroid subjects. Best practice & research Clinical endocrinology & metabolism 2005; 19(1):1-15.
  63. Stagnaro-Green A, Pearce E. Thyroid disorders in pregnancy. Nature Reviews Endocrinology 2012; 8(11):650-8.
  64. Qiu C, Sorensen TK, Luthy DA, Williams MA. A prospective study of maternal serum C‐reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatric and perinatal epidemiology 2004; 18(5):377-84.
  65. Wolf M, Sandler L, Hsu K, Vossen-Smirnakis K, Ecker JL, Thadhani R. First-trimester C-reactive protein and subsequent gestational diabetes. Diabetes care 2003; 26(3):819-24.
  66. Galofré JC, Pujante P, Abreu C, Santos S, Guillen-Grima F, Frühbeck G, et al. Relationship between thyroid-stimulating hormone and insulin in euthyroid obese men. Annals of Nutrition and Metabolism 2008; 53(3-4):188-94.
  67. Vitacolonna E, Lapolla A, Di Nenno B, Passante A, Bucci I, Giuliani C, et al. Gestational diabetes and thyroid autoimmunity. International journal of endocrinology 2012; 2012.
  68. Chen LM, Zhang Q, Si GX, Chen QS, Ye EL, Yu LC, et al. Associations between thyroid autoantibody status and abnormal pregnancy outcomes in euthyroid women. Endocrine 2015; 48(3):924-8.
  69. Montaner P, Juan L, Campos R, Gil L, Corcoy R. Is thyroid autoimmunity associated with gestational diabetes mellitus?. Metabolism 2008; 57(4):522-5.
  70. Gong LL, Liu H, Liu LH. Relationship between hypothyroidism and the incidence of gestational diabetes: A meta-analysis. Taiwanese Journal of Obstetrics and Gynecology 2016; 55(2):171-5.
  71. Maraka S, Ospina NM, O'Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, Coddington III CC, Stan MN, Murad MH, Montori VM. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid. 2016 Apr 1;26(4):580-90.
  72. Jia M, Wu Y, Lin B, Shi Y, Zhang Q, Lin Y, et al. Meta-analysis of the association between maternal subclinical hypothyroidism and gestational diabetes mellitus. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 2019; 144(3):239-47.
  73. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, 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(3):315-89.