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Adipocytokines mark insulin sensitivity in euthyroid Hashimoto’s patients

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Abstract

The relationship between inflammation, Hashimoto’s thyroiditis (HT) and insulin resistance is still controversial. In this regard, a pretty complete evaluation of adipocytokines levels in patients with HT has not been performed so far. We assessed retinol binding protein-4 (RBP4), adipocyte-fatty acid binding protein (A-FABP), neutrophil gelatinase–associated lipocalin (NGAL) and tumor necrosis factor-α (TNFα) levels in 93 euthyroid HT patients and 51 healthy controls (CTL), also evaluating the possible correlation between adipocytokines levels and markers of insulin resistance. No significant differences between HT patients and CTL in fasting plasma glucose and insulin levels, and HOMA index were observed. HT patients had significantly higher RBP4, NGAL and A-FABP levels than CTL, while TNFα levels did not differ between the two groups. In HT patients, RBP4 was significantly related with fT3 and fT4 levels, while A-FABP with fT4 only. Moreover, in HT patients, either RBP4 or A-FABP was directly associated with plasma insulin and HOMA index. Circulating levels of these adipocytokines were not influenced by the presence of antithyroid peroxidase or antithyroglobulin autoantibodies or only one of them, neither by autoantibodies titer. In conclusion, euthyroid HT patients are characterized by a peculiar inflammatory response of the adipose tissue, apparently related to an early reduction in insulin sensitivity and to serum thyroid hormone levels, although within the normal range. These results suggest that HT patients with high RBP4 and A-FABP levels might deserve a particular attention, being potentially more exposed to develop insulin resistance and increased cardiovascular risk.

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References

  1. Esteve E, Ricart W, Fernández-Real JM (2009) Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes Care 32(Suppl 2):S362–S367

    Article  PubMed  CAS  Google Scholar 

  2. Suh JB, Kim SM, Cho GJ, Choi KM, Han JH, Taek Geun H (2010) Elevated serum retinol-binding protein 4 is associated with insulin resistance in older women. Metabolism 59:118–122

    Article  PubMed  CAS  Google Scholar 

  3. Cheng X, Zhang H (2009) Serum retinal-binding protein 4 is positively related to insulin resistance in Chinese subjects with type 2 diabetes. Diabetes Res Clin Pract 84:58–60

    Article  PubMed  CAS  Google Scholar 

  4. Solini A, Santini E, Madec S, Rossi C, Muscelli E (2009) Retinol-binding protein-4 in women with untreated essential hypertension. Am J Hypertens 22:1001–1006

    Article  PubMed  CAS  Google Scholar 

  5. Aigner E, Bachofner N, Klein K, De Geyter C, Hohla F, Patsch W, Datz C (2009) Retinol-binding protein 4 in polycystic ovary syndrome-association with steroid hormones and response to pioglitazone treatment. J Clin Endocrinol Metab 94:1229–1235

    Article  PubMed  CAS  Google Scholar 

  6. Bolignano D, Coppolino G, Lacquaniti A, Buemi M (2010) From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrology. Eur J Clin Invest 40:273–276

    Article  PubMed  CAS  Google Scholar 

  7. Peters HP, Waanders F, Meijer E, van den Brand J, Steenbergen EJ, van Goor H, Wetzels JF (2011) High urinary excretion of kidney injury molecule-1 is an independent predictor of end-stage renal disease in patients with IgA nephropathy. Nephrol Dial Transplant 26:3581–3588

    Article  PubMed  CAS  Google Scholar 

  8. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, Nicocia G, Buemi M (2009) Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol 4:337–344

    Article  PubMed  CAS  Google Scholar 

  9. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, Xu A (2007) Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 53:34–41

    Article  PubMed  CAS  Google Scholar 

  10. Catalán V, Gómez-Ambrosi J, Rodríguez A, Ramírez B, Silva C, Rotellar F, Gil MJ, Cienfuegos JA, Salvador J, Frühbeck G (2009) Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans. J Mol Med 87:803–813

    Article  PubMed  Google Scholar 

  11. Choi KM, Lee JS, Kim EJ, Baik SH, Seo HS, Choi DS, Oh DJ, Park CG (2008) Implication of lipocalin-2 and visfatin levels in patients with coronary heart disease. Eur J Endocrinol 158:203–207

    Article  PubMed  CAS  Google Scholar 

  12. Simón I, Escoté X, Vilarrasa N, Gómez J, Fernández-Real JM, Megía A, Gutiérrez C, Gallart L, Masdevall C, Vendrell J (2009) Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. Obesity 17:1124–1128

    PubMed  Google Scholar 

  13. Tso AV, Xu A, Sham PC, Wat NM, Wang Y, Fong CH, Cheung BM, Janus ED, Lam KS (2007) Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabetes Care 30:2667–2672

    Article  PubMed  CAS  Google Scholar 

  14. Xu A, Tso AW, Cheung BM, Wang Y, Wat NM, Fong CH, Yeung DC, Janus ED, Sham PC, Lam KS (2007) Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 115:1537–1543

    Article  PubMed  CAS  Google Scholar 

  15. Choi KM, Yannakoulia M, Park MS, Cho GJ, Kim JH, Lee SH, Hwang TG, Yang SJ, Kim TN, Yoo HJ, Baik SH, Kim SM, Mantzoros CS (2011) Serum adipocyte fatty acid-binding protein, retinol-binding protein 4, and adiponectin concentrations in relation to the development of the metabolic syndrome in Korean boys: a 3-year prospective cohort study. Am J Clin Nutr 93:19–26

    Article  PubMed  CAS  Google Scholar 

  16. Lambadiari V, Mitrou P, Maratou E, Raptis AE, Tountas N, Raptis SA, Dimitriadis G (2011) Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes. Endocrine 39:28–32

    Article  PubMed  CAS  Google Scholar 

  17. Wang JY, Wang CY, Pei D, Lai CC, Chen YL, Wu CZ, Chang YL, Hsu CH, Pei C, Tang SH (2010) Association between thyroid function and metabolic syndrome in elderly subjects. J Am Geriatr Soc 58:1613–1614

    Article  PubMed  Google Scholar 

  18. Mueller A, Schöfl C, Dittrich R, Cupisti S, Oppelt PG, Schild RL, Beckmann MW, Häberle L (2009) Thyroid-stimulating hormone is associated with insulin resistance independently of body mass index and age in women with polycystic ovary syndrome. Hum Reprod 24:2924–2930

    Article  PubMed  CAS  Google Scholar 

  19. Lin Y, Sun Z (2011) Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes. Br J Pharmacol 162:597–610

    Article  PubMed  CAS  Google Scholar 

  20. Aksoy DY, Yürekli BP, Yildiz BO, Gedik O (2006) Prevalence of glutamic acid decarboxylase antibody positivity and its association with insulin secretion and sensitivity in autoimmune thyroid disease: a pilot study. Exp Clin Endocrinol Diabetes 114:412–416

    Article  PubMed  CAS  Google Scholar 

  21. Gjedde S, Gormsen LC, Rungby J, Nielsen S, Jørgensen JO, Pedersen SB, Riis AL, Weeke J, Møller N (2010) Decreased lipid intermediate levels and lipid oxidation rates despite normal lipolysis in patients with hypothyroidism. Thyroid 20:843–849

    Article  PubMed  CAS  Google Scholar 

  22. Ganie MA, Marwaha RK, Aggarwal R, Singh S (2010) High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case-control study. Eur J Endocrinol 162:1117–1122

    Article  PubMed  CAS  Google Scholar 

  23. Inoue N, Watanabe M, Nanba T, Wada M, Akamizu T, Iwatani Y (2009) Involvement of functional polymorphisms in the TNFA gene in the pathogenesis of autoimmune thyroid diseases and production of anti-thyrotropin receptor antibody. Clin Exp Immunol 156:199–204

    Article  PubMed  CAS  Google Scholar 

  24. Aust G, Heuer M, Laue S, Lehmann I, Hofmann A, Heldin NE, Scherbaum WA (1996) Expression of tumour necrosis factor-alpha (TNF-alpha) mRNA and protein in pathological thyroid tissue and carcinoma cell lines. Clin Exp Immunol 105:148–154

    Article  PubMed  CAS  Google Scholar 

  25. Türemen EE, Çetinarslan B, Şahin T, Cantürk Z, Tarkun İ (2011) Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocr J 58:349–354

    Article  PubMed  Google Scholar 

  26. Jiskra J, Antosová M, Límanová Z, Telicka Z, Lacinová Z (2009) The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases. Clin Exp Immunol 156:211–216

    Article  PubMed  CAS  Google Scholar 

  27. Bossowski A, Sawicka B, Szalecki M, Koput A, Wysocka J, Zelazowska-Rutkowska B (2010) Analysis of serum adiponectin, resistin and leptin levels in children and adolescents with autoimmune thyroid disorders. J Pediatr Endocrinol Metab 23:369–377

    Article  PubMed  CAS  Google Scholar 

  28. Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, Mitrou P, Lambadiari V, Boutati E, Nikzas D, Tountas N, Economopoulos T, Raptis SA, Dimitriadis G (2009) Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 160:785–790

    Article  PubMed  CAS  Google Scholar 

  29. Krassas GE, Pontikides N, Loustis K, Koliakos G, Constantinidis T, Kaltsas T (2006) Resistin levels are normal in hypothyroidism and remain unchanged after attainment of euthyroidism: relationship with insulin levels and anthropometric parameters. J Endocrinol Invest 29:606–612

    PubMed  CAS  Google Scholar 

  30. Choi SH, Lee YJ, Park YJ, Kim KW, Lee EJ, Lim S, Park do J, Kim SE, Park KS, Jang HC, Cho BY (2008) Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance. J Clin Endocrinol Metab 93:2313–2318

    Article  PubMed  CAS  Google Scholar 

  31. Bao Y, Lu Z, Zhou M, Li H, Wang Y, Gao M, Wei M, Jia W (2011) Serum levels of adipocyte fatty acid-binding protein are associated with the severity of coronary artery disease in Chinese women. PLoS One 6:e19115

    Article  PubMed  CAS  Google Scholar 

  32. Nakagawa S, Kawashima Y, Hirose A, Kozuka H (1994) Regulation of hepatic level of fatty-acid-binding protein by hormones and clofibric acid in the rat. Biochem J 297:581–584

    PubMed  CAS  Google Scholar 

  33. Iannetti A, Pacifico F, Acquaviva R, Lavorgna A, Crescenzi E, Vascotto C, Tell G, Salzano AM, Scaloni A, Vuttariello E, Chiappetta G, Formisano S, Leonardi A (2008) The neutrophil gelatinase-associated lipocalin (NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells. Proc Natl Acad Sci USA 105:14058–14063

    Article  PubMed  CAS  Google Scholar 

  34. Kimmel M, Braun N, Alscher MD (2011) Influence of thyroid function on different kidney function tests. Kidney Blood Press Res 35:9–17

    Article  PubMed  Google Scholar 

  35. Erden S, Buyukozturk S, Vural P, Değirmencioğlu S (2008) Acute-phase reactants in Hashimoto thyroiditis. Int Immunopharmacol 8:1863–1865

    Article  PubMed  CAS  Google Scholar 

  36. Bazzichi L, Rossi A, Zirafa C, Monzani F, Tognini S, Dardano A, Santini F, Tonacchera M, De Servi M, Giacomelli C, De Feo F, Doveri M, Massimetti G, Bombardieri S (2012) Thyroid autoimmunity may represent a predisposition for the development of fibromyalgia? Rheumatol Int 32:335–341

    Article  PubMed  CAS  Google Scholar 

  37. Dardano A, Bazzichi L, Bombardieri S, Monzani F (2011) Symptoms in euthyroid Hashimoto’s thyroiditis: is there a role for autoimmunity itself? Thyroid PMID: 22191404

  38. Nielsen CH, Brix TH, Leslie RG, Hegedüs L (2009) A role for autoantibodies in enhancement of pro-inflammatory cytokine responses to a self-antigen, thyroid peroxidase. Clin Immunol 133:218–227

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Anna Solini.

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Solini, A., Dardano, A., Santini, E. et al. Adipocytokines mark insulin sensitivity in euthyroid Hashimoto’s patients. Acta Diabetol 50, 73–80 (2013). https://doi.org/10.1007/s00592-012-0399-9

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  • DOI: https://doi.org/10.1007/s00592-012-0399-9

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