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Relationship between subclinical hypothyroidism and serum osteoprotegerin level in type 2 diabetic patients



Subclinical hypothyroidism (SCH) and osteoprotegerin (OPG) are associated with higher risks of cardiovascular disorders in patients with type 2 diabetes mellitus (T2DM). It is unknown whether diabetic patients with SCH have elevated OPG compared with those with euthyroid and, if so, whether SCH independently associated with OPG level.


The objective was to study the association between SCH and serum OPG level among Egyptian adults with newly diagnosed T2DM.

Patients and methods

One hundred and fifty patients with newly diagnosed T2DM and 150 healthy controls matched for sex and age were included in the study. Serum OPG, thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, blood glucose, lipid profile, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and anthropometric measurements were assessed for all participants.


The prevalence of SCH and elevated level of OPG in the diabetic patients were higher than healthy controls (17.3 vs. 4%, P <0.001; and 14 vs. 4.7%, P=0.02; respectively). Diabetics with SCH demonstrated significantly higher HOMA-IR, serum TSH, and OPG compared with diabetics without SCH. Serum TSH was significantly correlated with total cholesterol (P=0.05), fasting insulin (P=0.01), HOMA-IR (P=0.01), and OPG (P=0.005). Moreover, serum OPG was correlated with waist circumference (P=0.01), fasting insulin (P=0.05), and HOMA-IR (P=0.02). Multiple logistic regression analysis revealed that SCH was associated with serum level of OPG independently of the other significant variables (β=2.49, P=0.01).


T2DM patients with SCH demonstrate higher level and independent association with serum OPG than those with euthyroid. This result might add new information about the causal relationship between SCH and cardiovascular disorders in such a population.


  1. 1

    Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 137:49–103.

    Google Scholar 

  2. 2

    Straka RJ, Liu LZ, Girase PS, DeLorenzo A, Chapman RH. Incremental cardiovascular costs and resource use associated with diabetes: osteoprotegerin in type 2 diabetes mellitus 63 an assessment of 29,863 patients in the US managed-care setting. Cardiovasc Diabetol 2009; 1:53–58.

    Article  Google Scholar 

  3. 3

    Wu W, Ren M, Cheng H, Li Y, Qi Y-Q, Yang C, Yan L. Prevention of macrovascular disease in patients with short-duration type 2 diabetes by multifactorial target control: an 8-year prospective study. Endocrine 2014; 47:485–492.

    CAS  Article  Google Scholar 

  4. 4

    Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89:309–319.

    CAS  Article  Google Scholar 

  5. 5

    Pérez de Ciriza C, Lawrie A, Varo N. Osteoprotegerin in cardiometabolic disorders. Int J Endocrinol 2015; 1:15.

    Google Scholar 

  6. 6

    Tousoulis D, Siasos G, Maniatis K, Oikonomou E, Kioufis S, Zaromitidou M, et al. Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int J Cardiol 2013; 1924:1924–1928.

    Article  Google Scholar 

  7. 7

    Stępień E, Wypasek E, Stopyra K, Konieczynska M, Przybyło M, Pasowicz M. Increased levels of bone remodeling biomarkers (osteoprotegerin and osteopontin) in hypertensive individuals. Clin Biochem 2011; 826: 831–844.

    Google Scholar 

  8. 8

    Makarović S, Makarović Z, Steiner R, Mihaljević I, Milas-Ahić J. Osteoprotegerin and vascular calcification: clinical and prognostic relevance. Coll Antropol 2015; 461:8–39.

    Google Scholar 

  9. 9

    Kadoglou NP, Gerasimidis T, Golemati S, Kapelouzou A, Karayannacos PE, Liapis CD. The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability. J Vasc Surg 2008; 47:55–62.

    Article  Google Scholar 

  10. 10

    Bernardi S, Fabris B, Thomas M, Toffoli B, Tikellis C, Candido R, et al. Osteoprotegerin increases in metabolic syndrome and promotes adipose tissue proinflammatory changes. Mol Cell Endocrinol 2014; 394:13–20.

    CAS  Article  Google Scholar 

  11. 11

    Suliburska J, Bogdanski P, Gajewska E, Kalmus G, Sobieska M, Samborski W. The association of insulin resistance with serum osteoprotegerin in obese adolescents. J Physiol Biochem 2013; 847:853–869.

    Google Scholar 

  12. 12

    Bharat DH, Gangte D, Lalnunpui, Premchand, Devi I, Singh W. Thyroid status in diabetes mellitus. J Glycomics Lipidomics 2013; 3:1.

    Google Scholar 

  13. 13

    Palma CC, Marco P, Veronica GN, Eliete LS, Maria FB, Luiz CP, et al. Prevalence of thyroid dysfunction in patients with diabetes mellitus. Diabetol Metab Syndr 2013; 5:58.

    Article  Google Scholar 

  14. 14

    Laloo D, Salam R. Thyroid dysfunction in type 2 diabetes mellitus: a retrospective study. Ind J Endocrinol Metabol 2012; 16:S334–S335.

    Google Scholar 

  15. 15

    Simon HS, Georg B, Leonidas HD, Fabio M, Robin PP, Salman R. et al. 2013 ETA Guideline: management of Subclinical hypothyroidism. Eur Thyroid J 2013; 2:215–228.

    Google Scholar 

  16. 16

    Chen HS, Wu TE, Jap TS, Lu RA, Wang ML, Chen RL. et al. Subclinical hypothyroidismis a risk factor for nephropathy and cardiovascular diseases in type 2 diabetic patients. Diabetic Med 2007; 24:1336–1344.

    CAS  Article  Google Scholar 

  17. 17

    Auer J, Berent R, Weber T, Lassnig E, Eber B. Thyroid function is associated with the presence and severity of coronary atherosclerosis. Clin Cardiol 2003; 26:569–573.

    CAS  Article  Google Scholar 

  18. 18

    Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metabol 2003; 88:2438–2444.

    CAS  Article  Google Scholar 

  19. 19

    Alkaç C, Alkaç B, Akbaş F, Aral H, Karagöz Y, Altunoğlu EG. Osteoprotegerin as a marker of atherosclerosis in type 1 and type 2 diabetic Patients. Turk J Med Sci 2015; 1306:1311–1345.

    Google Scholar 

  20. 20

    Esteghamati A, Sheikhbahaei S, Hafezi-Nejad N, Mousavizadeh M, Noshad S, Larimi NG, et al. Serum osteoprotegerin in relation to metabolic status, severity, and estimated risk of subsequent coronary heart Disease. Arch Iran Med 2014; 596:601–617.

    Google Scholar 

  21. 21

    Hosbond SE, Diederichsen AC, Saaby L, Rasmussen LM, Lambrechtsen J, Munkholm H, et al. Can osteoprotegerin be used to identify the presence and severity of coronary artery disease in different clinical settings? Atherosclerosis 2014; 236:230–236.

    CAS  Article  Google Scholar 

  22. 22

    Friedewald WT, Levy RT, Fredrickson DS. Estimation of the concentration of low- density lipoprotein cholesterol without the use of preparative ultracentrifuge. Clin Chem 1972; 18:499.

    CAS  Article  Google Scholar 

  23. 23

    Matthews DR, Hosler JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985; 412:419–428.

    Google Scholar 

  24. 24

    Chubb SA, Davis WA, Davis TM. Interactions among thyroid function, insulin sensitivity, and serum lipid concentrations: the Fremantle diabetes study. J Clin Endocrinol Metab 2005; 5317:20–90.

    Google Scholar 

  25. 25

    Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 2009; 160:785–790.

    CAS  Article  Google Scholar 

  26. 26

    Berezin AE, Kremzer AA, Martovitskaya YV, Samura TA, Berezina TA, Zulli A, et al. The utility of biomarker risk prediction score in patients with chronic heart failure. Int J Clin Exp Med 2015; 18255:66.

    Google Scholar 

  27. 27

    Grais IM, Sowers JR. Thyroid and the heart. Am J Med 2014; 127:691–698.

    CAS  Article  Google Scholar 

  28. 28

    Iervasi G, Molinaro S, Landi P, Taddei MC, Galli E, Mariani F, et al. Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med 2007; 167:1526–1532.

    Article  Google Scholar 

  29. 29

    Evrard S, Delanaye P, Kamel S, Cristol JP, Cavalier E. Vascular calcification: from pathophysiology to biomarkers. Clin Chim Acta 2015; 401:14–438.

    Google Scholar 

  30. 30

    Pepene CE, Ilie IR, Marian I, Duncea I. Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction. Eur J Endocrinol 2011; 61:68–164.

    Google Scholar 

  31. 31

    Nagasaki T, Inaba M, Jono S, Hiura Y, Tahara H, Shirakawa K, et al. Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function. Eur J Endocrinol 2005; 152:347–353.

    CAS  Article  Google Scholar 

  32. 32

    Vargas F, Moreno JM, Rodriguez-Gomez I, Wangensteen R, Osuna A, Alvarez-Guerra M, Garcia-Estan J. Vascular and renal function in experimental thyroid disorders. Eur J Endocrinol 2006; 154:197–212.

    CAS  Article  Google Scholar 

  33. 33

    Biondi B, Galderisi M, Pagano L, Sidiropulos M, Pulcrano M, De A, et al. Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency. Eur J Endocrinol 2009; 161:323–329.

    CAS  Article  Google Scholar 

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Correspondence to Eman H. El-Adawy.

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El-Adawy, E.H., Shaker, G.A. & Seleem, A. Relationship between subclinical hypothyroidism and serum osteoprotegerin level in type 2 diabetic patients. Egypt J Intern Med 29, 176–180 (2017).

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  • cardiovascular disorders
  • osteoprotegerin
  • subclinical hypothyroidism
  • type 2 diabetes