Top

International Urology and Nephrology

Published in:

01-01-2018 | Nephrology - Original Paper

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

Authors: Yong Chen, Ganlin Wu, Meirong Xu

Published in: International Urology and Nephrology | Issue 1/2018

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.

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

13.

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

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

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 CrossRefPubMed

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 CrossRefPubMed

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

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 8:426–435PubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMed

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

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 CrossRefPubMed

Title: 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
Authors: Yong Chen
Ganlin Wu
Meirong Xu
Publication date: 01-01-2018
Publisher: Springer Netherlands
Published in: International Urology and Nephrology / Issue 1/2018
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI: https://doi.org/10.1007/s11255-017-1756-y

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2018

Does green tea consumption increase urinary oxalate excretion? Results of a prospective trial in healthy men

Changes observed in urine microbiology following replacement of long-term urinary catheters: need to modify UTI guidelines in the UK?

Improved cancer-specific free survival and overall free survival in contemporary metastatic prostate cancer patients: a population-based study

Water, electrolyte, acid–base, and trace elements alterations in cirrhotic patients

Preoperative urine culture is unnecessary in asymptomatic men prior to prostate needle biopsy

Does the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 improve accuracy in reporting anterior lesions on multiparametric magnetic resonance imaging (mpMRI)?

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page