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The effect of l-thyroxine substitution on oxidative stress in early-stage diabetic nephropathy patients with subclinical hypothyroidism: a randomized double-blind and placebo-controlled study

  • Nephrology - Original Paper
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Abstract

Purpose

To study oxidative stress status of early type 2 diabetic nephropathy (DN) patients with subclinical hypothyroidism (SCH) and to assess effect of l-thyroxine therapy on the oxidative stress in these patients.

Methods

It is a randomized double-blind and placebo-controlled trial. A total of 48 patients with early type 2 DN were included as Euthyroid group, and 92 early type 2 DN with SCH were selected and randomly assigned to l-thyroxine treatment group (LT4 group) and placebo group (SCH group). Changes in urinary albumin excretion rate (UAER), serum malondialdehyde (MDA), superoxide dismutase (SOD) activity, urine 8-hydroxyl deoxyguanosine (8-OHdG), serum creatinine, estimated glomerular filtration rate, and lipid profile before and after 24 weeks of follow-up were examined and compared.

Results

The levels of UAER, MDA, 8-OHdG were higher, while the SOD activity was lower in DN patients with SCH than in DN patients (p < 0.05 for all). In the LT4 group, the levels of UAER, MDA, 8-OHdG decreased significantly (p < 0.05) to levels no longer different from the Euthyroid group. The SOD activity increased significantly. But in SCH group, the levels of mAlb, MDA, 8-OHdG were greater after 24 weeks of follow-up and greater than patients in the Euthyroid group. SOD activity decreased significantly after 24 weeks in the SCH group (p < 0.05).

Conclusion

Oxidative stress is greater in the DN patients with SCH, and SCH may exacerbate kidney injury in early DN patients. The LT4 treatment may decrease the oxidative stress and attenuate renal injury in DN patient with SCH.

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References

  1. Mansournia N, Riyahi S, Tofangchiha S, Mansournia MA, Riahi M, Heidari Z, Hazrati E (2017) Subclinical hypothyroidism and diabetic nephropathy in Iranian patients with type 2 diabetes. J Endocrinol Invest 40:289–295. https://doi.org/10.1007/s40618-016-0560-3

    Article  CAS  PubMed  Google Scholar 

  2. Furukawa S, Yamamoto S, Todo Y, Maruyama K, Miyake T, Ueda T, Niiya T, Senba T, Torisu M, Kumagi T, Miyauchi S, Sakai T, Minami H, Miyaoka H, Matsuura B, Hiasa Y, Onji M, Tanigawa T (2014) Association between subclinical hypothyroidism and diabetic nephropathy in patients with type 2 diabetes mellitus. Endocr J 61:1011–1018. https://doi.org/10.1507/endocrj.EJ14-0206

    Article  CAS  PubMed  Google Scholar 

  3. Han C, He X, Xia X, Li Y, Shi X, Shan Z, Teng W (2015) Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis. PLoS ONE 10:e0135233. https://doi.org/10.1371/journal.pone.0135233

    Article  PubMed  PubMed Central  Google Scholar 

  4. Denzer C, Karges B, Näke A, Rosenbauer J, Schober E, Schwab KO, Holl RW, Initiative DPV, DPV Initiative and the BMBF-Competence Network Diabetes Mellitus (2013) Subclinical hypothyroidism and dyslipidemia in children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol 168:601–608. https://doi.org/10.1530/EJE-12-0703

    Article  CAS  PubMed  Google Scholar 

  5. Chen HS, Wu TE, Jap TS, Lu RA, Wang ML, Chen RL, Lin HD (2007) Subclinical hypothyroidism is a risk factor for nephropathy and cardiovascular diseases in Type 2 diabetic patients. Diabet Med 24:1336–1344. https://doi.org/10.1111/j.1464-5491.2007.02270.x

    Article  CAS  PubMed  Google Scholar 

  6. Ha H, Kim KH (1999) Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C. Diabetes Res Clin Pract 45:147–151. https://doi.org/10.1016/S0168-8227(99)00044-3

    Article  CAS  PubMed  Google Scholar 

  7. Aydogdu A, Karakas EY, Erkus E, Altıparmak İH, Savık E, Ulas T, Sabuncu T (2017) Epicardial fat thickness and oxidative stress parameters in patients with subclinical hypothyroidism. Arch Med Sci 13:383. https://doi.org/10.5114/aoms.2017.65479

    Article  PubMed  PubMed Central  Google Scholar 

  8. Liu P, Liu R, Chen X, Chen Y, Wang D, Zhang F, Wang Y (2015) Can levothyroxine treatment reduce urinary albumin excretion rate in patients with early type 2 diabetic nephropathy and subclinical hypothyroidism? A randomized double-blind and placebo-controlled study. Curr Med Res Opin 31:2233–2240. https://doi.org/10.1185/03007995.2015.1094044

    Article  CAS  PubMed  Google Scholar 

  9. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC (2000) Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 132:270–278. https://doi.org/10.7326/0003-4819-132-4-200002150-00004

    Article  CAS  PubMed  Google Scholar 

  10. Shin DH, Lee MJ, Kim SJ, Oh HJ, Kim HR, Han JH, Koo HM, Doh FM, Park JT, Han SH, Yoo TH, Kang SW (2012) Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism. J Clin Endocrinol Metab 97:2732–2740. https://doi.org/10.1210/jc.2012-1663

    Article  CAS  PubMed  Google Scholar 

  11. Yasuda T, Kaneto H, Kuroda A, Yamamoto T, Takahara M, Naka T, Miyashita K, Fujisawa K, Sakamoto F, Katakami N, Matsuoka TA, Shimomura I (2011) Subclinical hypothyroidism is independently associated with albuminuria in people with type 2 diabetes. Diabetes Res Clin Pract 94:e75–e77. https://doi.org/10.1016/j.diabres.2011.08.019

    Article  CAS  PubMed  Google Scholar 

  12. El-Eshmawy MM, Abd El-Hafez HA, El Shabrawy WO, Abdel Aal IA (2013) Subclinical hypothyroidism is independently associated with microalbuminuria in a cohort of prediabetic egyptian adults. Diabetes Metab J 37:450–457. https://doi.org/10.4093/dmj.2013.37.6.450

    Article  PubMed  PubMed Central  Google Scholar 

  13. Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412

    Article  CAS  PubMed  Google Scholar 

  14. Control D, Group CTR (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993:977–986. https://doi.org/10.2337/diab.40.4.405

    Google Scholar 

  15. Wolff SP, Jiang ZY, Hunt JV (1991) Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 10:339–352. https://doi.org/10.1016/0891-5849(91)90040-A

    Article  CAS  PubMed  Google Scholar 

  16. Ha H, Kim C, Son Y, Chung M-H, Kim KH (1994) DNA damage in the kidneys of diabetic rats exhibiting microalbuminuria. Free Radic Biol Med 16:271–274. https://doi.org/10.1016/0891-5849(94)90152-X

    Article  CAS  PubMed  Google Scholar 

  17. Ha H, Kim K (1997) Role of protein kinase C-mediated oxidative stress in increased TGF-β1 and fibronectin mRNAs in mesangial cells: implications for diabetic nephropathy. Nephrology 3:A736

    Google Scholar 

  18. Koya D, Lee I-K, Ishii H, Kanoh H, King GL (1997) Prevention of glomerular dysfunction in diabetic rats by treatment with d-alpha-tocopherol. J Am Soc Nephrol 8:426–435

    CAS  PubMed  Google Scholar 

  19. Ha H, Yu M-R, Kim KH (1999) Melatonin and taurine reduce early glomerulopathy in diabetic rats. Free Radic Biol Med 26:944–950. https://doi.org/10.1016/S0891-5849(98)00276-7

    Article  CAS  PubMed  Google Scholar 

  20. Oziol L, Faure P, Bertrand N, Chomard P (2003) Inhibition of in vitro macrophage-induced low density lipoprotein oxidation by thyroid compounds. J Endocrinol 177:137–146. https://doi.org/10.1677/joe.0.1770137

    Article  CAS  PubMed  Google Scholar 

  21. Pereira B, Rosa LC, Safi D, Bechara E, Curi R (1994) Control of superoxide dismutase, catalase and glutathione peroxidase activities in rat lymphoid organs by thyroid hormones. J Endocrinol 140:73–77. https://doi.org/10.1677/joe.0.1400073

    Article  CAS  PubMed  Google Scholar 

  22. Yilmaz S, Ozan S, Benzer F, Canatan H (2003) Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism. Cell Biochem Funct 21:325–330. https://doi.org/10.1002/cbf.1031

    Article  CAS  PubMed  Google Scholar 

  23. Kebapcilar L, Akinci B, Bayraktar F, Comlekci A, Solak A, Demir T, Yener S, Küme T, Yesil S (2007) Plasma thiobarbituric acid-reactive substance levels in subclinical hypothyroidism. Med Princ Pract 16:432–436. https://doi.org/10.1159/000107747

    Article  PubMed  Google Scholar 

  24. Torun AN, Kulaksizoglu S, Kulaksizoglu M, Pamuk BO, Isbilen E, Tutuncu NB (2009) Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol (Oxf) 70:469–474. https://doi.org/10.1111/j.1365-2265.2008.03348.x

    Article  Google Scholar 

  25. Jena S, Chainy GBN, Dandapat J (2012) Hypothyroidism modulates renal antioxidant gene expression during postnatal development and maturation in rat. Gen Comp Endocrinol 178:8–18. https://doi.org/10.1016/j.ygcen.2012.03.012

    Article  CAS  PubMed  Google Scholar 

  26. Baskol G, Atmaca H, Tanrıverdi F, Baskol M, Kocer D, Bayram F (2007) Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. Exp Clin Endocrinol Diabetes 115:522–526. https://doi.org/10.1055/s-2007-981457

    Article  CAS  PubMed  Google Scholar 

  27. Mutlu S, Parlak A, Aydogan U, Aydogdu A, Soykut B, Akay C, Saglam K, Taslipinar A (2013) The effect of levothyroxine replacement therapy on lipid profile and oxidative stress parameters in patients with subclinical hypothyroid. Arch Pharm Res. https://doi.org/10.1007/s12272-013-0227-y

    PubMed  Google Scholar 

  28. Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, Xu JS, Huang SM, Wang LN, Huang W, Wang M, Xu GB, Wang HY (2006) Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 17:2937–2944. https://doi.org/10.1681/ASN.2006040368

    Article  PubMed  Google Scholar 

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Correspondence to Ganlin Wu.

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This research was approved by the ethics committee of the Xian’ning Central Hospital, The First Affiliated Hospital of Hubei University Of Science And Technology (No. XNLL-2014001) on March 17, 2014, and performed with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Chen, Y., Wu, G. & Xu, M. The effect of l-thyroxine substitution on oxidative stress in early-stage diabetic nephropathy patients with subclinical hypothyroidism: a randomized double-blind and placebo-controlled study. Int Urol Nephrol 50, 97–103 (2018). https://doi.org/10.1007/s11255-017-1756-y

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