open access
Is thyroid autoimmunity associated with subclinical atherosclerosis in young women with type 1 diabetes mellitus?
, 3, 24, 1, 1
Affiliations- Department of Diabetology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Internal Diseases, Endocrinology, and Diabetology, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland
- Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw, Poland
- Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
open access
Abstract
Introduction: It has been hypothesized that autoimmunity may contribute to cardiovascular complications and may be an important trigger for processes leading to atherosclerosis, especially in type 1 diabetes mellitus (T1DM). This pilot study aimed to answer the question of whether markers of thyroid autoimmunity are associated with increased carotid intima-media thickness (cIMT) in young, asymptomatic T1DM women.
Material and methods: The study population consisted of 102 women, including 72 with T1DM and 30 healthy controls. All patients had thyroid hormones within the normal range. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO-positive (T1DM aTPO+) (n = 41) and an aTPO-negative (T1DM aTPO–) (n = 31) group. In all patients, aTPO, thyroglobulin antibody (aTG) titres, thyroid-stimulating hormone (TSH), free thyroxine (FT3), free triiodothyronine (FT4), lipid parameters, glycated haemoglobin, thyroid ultrasonography, and cIMT assessment were evaluated. The association of cIMT with different risk factors related to thyroid autoimmunity was determined.
Results: Carotid intima-media thickness was significantly greater in T1DM aTPO+ females (0.66 ± 0.10 mm) than in T1DM aTPO– (0.59 ± 0.11 mm) and healthy controls (0.58 ± 0.10 mm) (p = 0.007, p = 0.001, respectively). In all women cIMT was significantly, positively correlated with aTPO (p = 0.005, r = 0.273), Hashimoto’s thyroiditis (HT) duration (p = 0.00015, r = 0.367), levothyroxine dose per week (p = 0.006, r = 0.269), and ultrasound features of HT (p = 0.004, r = 0.281) and inversely with fT3 concentration (p = 0.014, r = –0.243) and FT3/FT4 ratio (p = 0.042, r = –0.201). A logistic regression analysis showed that HT duration (OR: 1.102, 95% CI: 1.008–1.206, p = 0.032) and a positive history family of HT (OR: 3.909, 95%CI: 1.014–15.071, p = 0.045) were risk factors for increased cIMT. However, multivariate regression analysis showed that the studied parameters related to thyroid autoimmunity are not independent risk factors for increased cIMT.
Conclusions: We expanded the data on cIMT in young women with T1DM and showed that thyroid autoimmunity, and in particular the duration of exposure to anti-thyroid antibodies, despite adequate levothyroxine substitution, is associated with subclinical atherosclerosis in young women with T1DM. However, thyroid-related parameters are not independent risk factors for increased cIMT in euthyroid women.
Abstract
Introduction: It has been hypothesized that autoimmunity may contribute to cardiovascular complications and may be an important trigger for processes leading to atherosclerosis, especially in type 1 diabetes mellitus (T1DM). This pilot study aimed to answer the question of whether markers of thyroid autoimmunity are associated with increased carotid intima-media thickness (cIMT) in young, asymptomatic T1DM women.
Material and methods: The study population consisted of 102 women, including 72 with T1DM and 30 healthy controls. All patients had thyroid hormones within the normal range. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO-positive (T1DM aTPO+) (n = 41) and an aTPO-negative (T1DM aTPO–) (n = 31) group. In all patients, aTPO, thyroglobulin antibody (aTG) titres, thyroid-stimulating hormone (TSH), free thyroxine (FT3), free triiodothyronine (FT4), lipid parameters, glycated haemoglobin, thyroid ultrasonography, and cIMT assessment were evaluated. The association of cIMT with different risk factors related to thyroid autoimmunity was determined.
Results: Carotid intima-media thickness was significantly greater in T1DM aTPO+ females (0.66 ± 0.10 mm) than in T1DM aTPO– (0.59 ± 0.11 mm) and healthy controls (0.58 ± 0.10 mm) (p = 0.007, p = 0.001, respectively). In all women cIMT was significantly, positively correlated with aTPO (p = 0.005, r = 0.273), Hashimoto’s thyroiditis (HT) duration (p = 0.00015, r = 0.367), levothyroxine dose per week (p = 0.006, r = 0.269), and ultrasound features of HT (p = 0.004, r = 0.281) and inversely with fT3 concentration (p = 0.014, r = –0.243) and FT3/FT4 ratio (p = 0.042, r = –0.201). A logistic regression analysis showed that HT duration (OR: 1.102, 95% CI: 1.008–1.206, p = 0.032) and a positive history family of HT (OR: 3.909, 95%CI: 1.014–15.071, p = 0.045) were risk factors for increased cIMT. However, multivariate regression analysis showed that the studied parameters related to thyroid autoimmunity are not independent risk factors for increased cIMT.
Conclusions: We expanded the data on cIMT in young women with T1DM and showed that thyroid autoimmunity, and in particular the duration of exposure to anti-thyroid antibodies, despite adequate levothyroxine substitution, is associated with subclinical atherosclerosis in young women with T1DM. However, thyroid-related parameters are not independent risk factors for increased cIMT in euthyroid women.
Keywords
type 1 diabetes; thyroid autoimmunity; anti-thyroid antibodies; atherosclerosis
About this articleTitle
Is thyroid autoimmunity associated with subclinical atherosclerosis in young women with type 1 diabetes mellitus?
Journal
Issue
Article type
Original paper
Pages
301-308
Published online
2022-04-05
Page views
2107
Article views/downloads
708
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2022;73(2):301-308.
Keywords
type 1 diabetes
thyroid autoimmunity
anti-thyroid antibodies
atherosclerosis
Authors
Magdalena Maria Łukawska-Tatarczuk
Jakub Zieliński
Edward Franek
Leszek Czupryniak
Beata Mrozikiewicz-Rakowska
References (41)- de Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014; 130(13): 1110–1130.
- Kozhakhmetova A, Wyatt RC, Caygill C, et al. A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study. Clin Exp Immunol. 2018; 192(3): 251–258.
- Łukawska-Tatarczuk M, Mrozikiewicz-Rakowska B, Franek E, et al. Molecular pathogenesis of heart failure in diabetes mellitus — new direction for the therapeutic approach. Postepy Hig Med Dosw. 2020; 74: 452–463.
- Lim H, Kim YUk, Sun H, et al. Proatherogenic conditions promote autoimmune T helper 17 cell responses in vivo. Immunity. 2014; 40(1): 153–165.
- İşgüven P, Gündüz Y, Kılıç M. Effects of Thyroid Autoimmunity on Early Atherosclerosis in Euthyroid Girls with Hashimoto's Thyroiditis. J Clin Res Pediatr Endocrinol. 2016; 8(2): 150–156.
- Moschonas IC, Tselepis AD. The pathway of neutrophil extracellular traps towards atherosclerosis and thrombosis. Atherosclerosis. 2019; 288: 9–16.
- Di Florio DN, Sin J, Coronado MJ, et al. Sex differences in inflammation, redox biology, mitochondria and autoimmunity. Redox Biol. 2020; 31: 101482.
- Madonna R, Balistreri CR, De Rosa S, et al. Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease. J Clin Med. 2019; 8(1).
- Wang Y, O'Neil A, Jiao Y, et al. Sex differences in the association between diabetes and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a systematic review and meta-analysis of 5,162,654 participants. BMC Med. 2019; 17(1): 136.
- Grant PJ, Cosentino F, Cosentino F, et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255–323.
- Kahaly GJ, Hansen MP. Type 1 diabetes associated autoimmunity. Autoimmun Rev. 2016; 15(7): 644–648.
- Stefanowicz-Rutkowska MM, Baranowska-Jurkun A, Matuszewski W, et al. Thyroid dysfunction in patients with diabetic retinopathy. Endokrynol Pol. 2020; 71(2): 176–183.
- Denzer C, Karges B, Näke A, et al. DPV Initiative and the BMBF-Competence Network Diabetes Mellitus. Subclinical hypothyroidism and dyslipidemia in children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol. 2013; 168(4): 601–608.
- Głowinska-Olszewska B, Borysewicz-Sańczyk H, Sawicka B, et al. Does Hashimoto's Thyroiditis Increase the Risk of Cardiovascular Disease in Young Type 1 Diabetic Patients? Front Endocrinol (Lausanne). 2020; 11: 431.
- Raterman HG, Voskuyl AE, Simsek S, et al. Increased progression of carotid intima media thickness in thyroid peroxidase antibodies-positive rheumatoid arthritis patients. Eur J Endocrinol. 2013; 169(6): 751–757.
- Trzebińska A, Dobruch-Sobczak K, Jakubowski W, et al. Standardy badań ultrasonograficznych Polskiego Towarzystwa Ultrasonografi cznego – aktualizacja. Badanie ultrasonografi czne tarczycy oraz biopsja tarczycy pod kontrolą ultrasonografi i. J Ultrasonography. 2014; 14(56): 49–60.
- Elwertowski M, Małek G. Standardy badań ultrasonograficznych Polskiego Towarzystwa Ultrasonograficznego – aktualizacja. Badanie zewnątrzczaszkowych odcinków tętnic szyjnych oraz kręgowych. J Ultrasonography. 2014; 14(57): 179–191.
- Carvalho GA, Perez CL, Ward LS. The clinical use of thyroid function tests. Arq Bras Endocrinol Metabol. 2013; 57(3): 193–204.
- Bilge M, Yesilova A, Adas M, et al. Neutrophil- and Platelet- to Lymphocyte Ratio in Patients with Euthyroid Hashimoto's Thyroiditis. Exp Clin Endocrinol Diabetes. 2019; 127(8): 545–549.
- Siemińska L, Wojciechowska C, Walczak K, et al. Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6. Endokrynol Pol. 2015; 66(5): 394–403.
- Ruggeri RM, Vicchio TM, Cristani M, et al. Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis. Thyroid. 2016; 26(4): 504–511.
- Janyga S, Marek B, Kajdaniuk D, et al. CD4+ cells in autoimmune thyroid disease. Endokrynol Pol. 2021; 72(5): 572–583.
- Pitocco D, Giubilato S, Martini F, et al. Combined atherogenic effects of celiac disease and type 1 diabetes mellitus. Atherosclerosis. 2011; 217(2): 531–535.
- Topaloglu O, Gokay F, Kucukler K, et al. Is autoimmune thyroiditis a risk factor for early atherosclerosis in premenopausal women even if in euthyroid status? Endocrine. 2013; 44(1): 145–151.
- Loizou CP, Nicolaides A, Kyriacou E, et al. A Comparison of Ultrasound Intima-Media Thickness Measurements of the Left and Right Common Carotid Artery. IEEE J Transl Eng Health Med. 2015; 3: 1900410.
- Head T, Daunert S, Goldschmidt-Clermont PJ. The Aging Risk and Atherosclerosis: A Fresh Look at Arterial Homeostasis. Front Genet. 2017; 8: 216.
- VanderBurgh JA, Reinhart-King CA. The Role of Age-Related Intimal Remodeling and Stiffening in Atherosclerosis. Adv Pharmacol. 2018; 81: 365–391.
- Milutinović A, Šuput D, Zorc-Pleskovič R. Pathogenesis of atherosclerosis in the tunica intima, media, and adventitia of coronary arteries: An updated review. Bosn J Basic Med Sci. 2020; 20(1): 21–30.
- Zhou Y, Zhao L, Wang T, et al. Free Triiodothyronine Concentrations are Inversely Associated with Elevated Carotid Intima-Media Thickness in Middle-Aged and Elderly Chinese Population. J Atheroscler Thromb. 2016; 23(2): 216–224.
- Wang L, Chen T, Yu J, et al. Clinical Associations of Thyroid Hormone Levels with the Risk of Atherosclerosis in Euthyroid Type 2 Diabetic Patients in Central China. Int J Endocrinol. 2020; 2020: 2172781.
- Fukuyama K, Ichiki T, Imayama I, et al. Thyroid hormone inhibits vascular remodeling through suppression of cAMP response element binding protein activity. Arterioscler Thromb Vasc Biol. 2006; 26(9): 2049–2055.
- Wang Po, DU R, Lin L, et al. Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants. Biomed Environ Sci. 2017; 30(2): 128–133.
- Park SoY, Park SeE, Jung SW, et al. Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects. Clin Endocrinol (Oxf). 2017; 87(1): 87–96.
- Štěpánek L, Horáková D, Štěpánek L, et al. Free triiodothyronine/free thyroxine (FT3/FT4) ratio is strongly associated with insulin resistance in euthyroid and hypothyroid adults: a cross-sectional study. Endokrynol Pol. 2021; 72(1): 8–13.
- Strich D, Chay C, Karavani G, et al. Levothyroxine Therapy Achieves Physiological FT3/FT4 Ratios at Higher than Normal TSH Levels: A Novel Justification for T3 Supplementation? Horm Metab Res. 2018; 50(11): 827–831.
- Ciccone MM, De Pergola G, Porcelli MT, et al. Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage? BMC Cardiovasc Disord. 2010; 10: 22.
- Tamer G, Mert M, Tamer I, et al. Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia. Endokrynol Pol. 2011; 62(5): 421–428.
- Liu J, Duan Y, Fu J, et al. Association Between Thyroid Hormones, Thyroid Antibodies, and Cardiometabolic Factors in Non-Obese Individuals With Normal Thyroid Function. Front Endocrinol (Lausanne). 2018; 9: 130.
- Li L, Liu S, Yu J. Autoimmune thyroid disease and type 1 diabetes mellitus: same pathogenesis; new perspective? Ther Adv Endocrinol Metab. 2020; 11: 2042018820958329.
- Fang Pu, Li X, Dai J, et al. Immune cell subset differentiation and tissue inflammation. J Hematol Oncol. 2018; 11(1): 97.
- Łukawska-Tatarczuk M, Franek E, Czupryniak L, et al. Sirtuin 1, Visfatin and IL-27 Serum Levels of Type 1 Diabetic Females in Relation to Cardiovascular Parameters and Autoimmune Thyroid Disease. Biomolecules. 2021; 11(8).
