{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T14:25:58Z","timestamp":1793888758691,"version":"4.8.0"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"abstract":"<jats:p>\n                    The relation between diabetes and thyroid dysfunction is multidimensional. The present study aimed to critically revise the published literature on the relation between thyroid hormone levels and diabetic peripheral neuropathy (DPN) in type II diabetes (T2DM) patients without clinical thyroid dysfunction. The present systematic review was performed in line with recommendations of the Preferred Reporting Items for Systematic review and Meta-Analyses guidelines. The review was conducted on 10 studies including 7559 patients. They comprised 2892 patients (38.3%) with DPN and 4667 patients (61.7%) without DPN. Pooled analysis revealed significantly lower FT3 levels in patients with DPN as compared to patients without DPN (standardized mean difference (SMD) (95% CI): \u22121.03 (\u22121.80, \u22120.25);\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.009). Also, it was shown that patients with DPN had significantly lower FT4 levels when compared with patients without DPN (SMD (95% CI): \u22120.27 (\u22120.50, \u22120.05);\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.02). However, no significant differences were found between the studied subgroups regarding pooled thyroid stimulating hormone (TSH) levels (SMD (95% CI): 0.21 (\u22120.08, 0.55);\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.15). Conclusively, in T2DM patients without clinical thyroid dysfunction, patients with DPN had significantly lower FT3 and FT4 levels, while TSH levels were comparable between patients with DPN and patients without.\n                  <\/jats:p>","DOI":"10.1177\/10815589261497357","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:20:36Z","timestamp":1791433236000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Relation between thyroid hormone levels and diabetic peripheral neuropathy in diabetic patients without clinical thyroid dysfunction: A systematic review and meta-analysis"],"prefix":"10.1177","author":[{"given":"Mohamed Ahmad","family":"Younes Hussein","sequence":"first","affiliation":[{"name":"Clinical Pathology Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mahmoud Abdullah","family":"Salem","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamada Hamdy Hassan","family":"Abdellatif","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mohammed Mostafa","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Aboud Omar","family":"Abo Zied","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Gamil Said","family":"Elgohary","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman Nooreldeen Mostafa","family":"Abdellateef","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Abdelaziz Elsayed Atiia","family":"Elhagary","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany Gamal Abozaid","family":"Metwaly","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdy Saeed Ahmed","family":"Othman","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman Noureldeen","family":"Abdelal","sequence":"additional","affiliation":[{"name":"Neurology Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman Sayed Ahmed Mohamed","family":"Ayad","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawashty Ragab","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Neurology Department, Al-Azhar University, Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","unstructured":"Zhang EX Yazdi C Islam RK et al. Diabetic neuropathy: a guide to pain management. Curr Pain Headache Rep 2024; 28(10): 1067\u20131072. https:\/\/doi.org\/10.1007\/s11916-024-01293-9","DOI":"10.1007\/s11916-024-01293-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","unstructured":"Lee JE Won JC. Clinical phenotypes of diabetic peripheral neuropathy: implications for phenotypic-based therapeutics strategies. Diabetes Metab J 2025; 49(4): 542\u2013564. https:\/\/doi.org\/10.4093\/dmj.2025.0299","DOI":"10.4093\/dmj.2025.0299"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","unstructured":"Savelieff MG Elafros MA Viswanathan V et al. The global and regional burden of diabetic peripheral neuropathy. Nat Rev Neurol 2025; 21(1): 17\u201331. https:\/\/doi.org\/10.1038\/s41582-024-01041-y","DOI":"10.1038\/s41582-024-01041-y"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","unstructured":"Tao Y Zhang HY MacGilchrist C et al. Prevalence and risk factors of painful diabetic neuropathy: a systematic review and meta-analysis. Diabetes Res Clin Pract 2025; 222: 112099. https:\/\/doi.org\/10.1016\/j.diabres.2025.112099","DOI":"10.1016\/j.diabres.2025.112099"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","unstructured":"Nashtahosseini Z Eslami M Paraandavaji E et al. Cytokine signaling in diabetic neuropathy: a key player in peripheral nerve damage. Biomedicines 2025; 13(3): 589. https:\/\/doi.org\/10.3390\/biomedicines13030589","DOI":"10.3390\/biomedicines13030589"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","unstructured":"Chong ZZ Souayah N. Neuroinflammation in diabetic peripheral neuropathy and therapeutic implications. Rev Neurosci 2025; 36(7): 749\u2013762. https:\/\/doi.org\/10.1515\/revneuro-2025-0031","DOI":"10.1515\/revneuro-2025-0031"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","unstructured":"Yang Y Zhao B Wang Y et al. Diabetic neuropathy: cutting-edge research and future directions. Signal Transduct Target Ther 2025; 10(1): 132. https:\/\/doi.org\/10.1038\/s41392-025-02175-1","DOI":"10.1038\/s41392-025-02175-1"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","unstructured":"Mohammed Hussein SM AbdElmageed RM. The relationship between type 2 diabetes mellitus and related thyroid diseases. Cureus 2021; 13(12): e20697. https:\/\/doi.org\/10.7759\/cureus.20697","DOI":"10.7759\/cureus.20697"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","unstructured":"Chauhan A Patel SS. Thyroid hormone and diabetes mellitus interplay: making management of comorbid disorders complicated. Horm Metab Res 2024; 56(12): 845\u2013858. https:\/\/doi.org\/10.1055\/a-2374-8756","DOI":"10.1055\/a-2374-8756"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","unstructured":"Hadgu R Worede A Ambachew S. Prevalence of thyroid dysfunction and associated factors among adult type 2 diabetes mellitus patients 2000-2022: a systematic review and meta-analysis. Syst Rev 2024; 13(1): 119. https:\/\/doi.org\/10.1186\/s13643-024-02527-y","DOI":"10.1186\/s13643-024-02527-y"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","unstructured":"Roa Due\u00f1as OH Van der Burgh AC Ittermann T et al. Thyroid function and the risk of prediabetes and type 2 diabetes. J Clin Endocrinol Metab 2022; 107(6): 1789\u20131798. https:\/\/doi.org\/10.1210\/clinem\/dgac006","DOI":"10.1210\/clinem\/dgac006"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"Amirabadizadeh A Ghorbani A Azizi F et al. Exploring the bidirectional association between thyrotropin and thyroid hormones in type 2 diabetes: a systematic review and meta-analysis. J Diabetes Metab Disord 2025; 24(1): 98. https:\/\/doi.org\/10.1007\/s40200-025-01612-w","DOI":"10.1007\/s40200-025-01612-w"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","unstructured":"Alwan H Villoz F Feller M et al. Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies. Eur J Endocrinol 2022; 187(5): S35\u2013S46. https:\/\/doi.org\/10.1530\/EJE-22-0523","DOI":"10.1530\/EJE-22-0523"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","unstructured":"Grigoriadis G Koufakis T Kotsa K. Epidemiological pathophysiological and clinical considerations on the interplay between thyroid disorders and type 2 diabetes mellitus. Medicina (Kaunas) 2023; 59(11): 2013. https:\/\/doi.org\/10.3390\/medicina59112013","DOI":"10.3390\/medicina59112013"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","unstructured":"Xu B Yang X Ma Y et al. Association between free triiodothyronine and diabetic peripheral neuropathy in euthyroid patients with type 2 diabetes. J Clin Endocrinol Metab 2025; 111(1): 119\u2013128. https:\/\/doi.org\/10.1210\/clinem\/dgaf304","DOI":"10.1210\/clinem\/dgaf304"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","unstructured":"He Q Zeng Z Zhao M et al. Association between thyroid function and diabetes peripheral neuropathy in euthyroid type 2 diabetes mellitus patients. Sci Rep 2023; 13(1): 13499. https:\/\/doi.org\/10.1038\/s41598-023-40752-y","DOI":"10.1038\/s41598-023-40752-y"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","unstructured":"Hu Y Hu Z Tang W et al. Association of thyroid hormone levels with microvascular complications in euthyroid type 2 diabetes mellitus patients. Diabetes Metab Syndr Obes 2022; 15: 2467\u20132477. https:\/\/doi.org\/10.2147\/DMSO.S354872","DOI":"10.2147\/DMSO.S354872"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","unstructured":"Page MJ McKenzie JE Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. J Clin Epidemiol 2021; 134: 178\u2013189. https:\/\/doi.org\/10.1016\/j.jclinepi.2021.03.001","DOI":"10.1016\/j.jclinepi.2021.02.003"},{"key":"e_1_3_4_20_2","unstructured":"Wells GA Shea B O\u2019Connell D et al. The Newcastle\u2013Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp (2014 accessed September 2025)."},{"key":"e_1_3_4_21_2","volume-title":"Cochrane handbook for systematic reviews of interventions","author":"Higgins JPT","year":"2023","unstructured":"Higgins JPT, Thomas J, Chandler J, et al, eds. Cochrane handbook for systematic reviews of interventions. Version 6.4. Cochrane, 2023."},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"Chen Y Sun L Chen M et al. Lower free triiodothyronine is a risk factor of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2024; 17: 4407\u20134415. https:\/\/doi.org\/10.2147\/DMSO.S489204","DOI":"10.2147\/DMSO.S489204"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","unstructured":"Fei SJ Luo JY Wang WH et al. Correlation between diabetic peripheral neuropathy and thyroid hormone sensitivity in elderly patients with type 2 diabetes mellitus. World J Diabetes 2025; 16(2): 98897. https:\/\/doi.org\/10.4239\/wjd.v16.i2.98897","DOI":"10.4239\/wjd.v16.i2.98897"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"Sun M Yu L Zhao X et al. Correlation between thyroid hormone sensitivity and diabetic peripheral neuropathy in euthyroid patients with type 2 diabetes mellitus. Sci Rep 2024; 14(1): 19603. https:\/\/doi.org\/10.1038\/s41598-024-70673-3","DOI":"10.1038\/s41598-024-70673-3"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","unstructured":"Jadhao P Swain J Das S et al. Prevalence and predictors of diabetic peripheral neuropathy in newly diagnosed type 2 diabetes mellitus patients. Curr Diabetes Rev 2025; 21(3): 13\u201323. https:\/\/doi.org\/10.2174\/0115733998282818240125110248","DOI":"10.2174\/0115733998282818240125110248"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","unstructured":"He W Pang C Chen L et al. Low T3 syndrome is associated with peripheral neuropathy in patients with type 2 diabetes mellitus. Muscle Nerve 2022; 66(6): 723\u2013729. https:\/\/doi.org\/10.1002\/mus.27719","DOI":"10.1002\/mus.27719"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","unstructured":"Li MF Ke JF Li S et al. Serum free triiodothyronine is inversely associated with diabetic peripheral neuropathy but not with carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes. Diabetol Metab Syndr 2021; 13(1): 142. https:\/\/doi.org\/10.1186\/s13098-021-00760-2","DOI":"10.1186\/s13098-021-00760-2"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","unstructured":"Zhao W Zeng H Zhang X et al. A high thyroid stimulating hormone level is associated with diabetic peripheral neuropathy in type 2 diabetes patients. Diabetes Res Clin Pract 2016; 115: 122\u2013129. https:\/\/doi.org\/10.1016\/j.diabres.2016.01.018","DOI":"10.1016\/j.diabres.2016.01.018"},{"key":"e_1_3_4_29_2","unstructured":"DeGroot LJ. The non-thyroidal illness syndrome. In: Feingold KR Ahmed SF Anawalt B et al. (eds) Endotext [Internet]. MDText.com Inc. 2000."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","unstructured":"Kovacevic M Nesek-Adam V Klokic S et al. Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: a prospective observational cohort study. World J Crit Care Med 2024; 13(3): 96132. https:\/\/doi.org\/10.5492\/wjccm.v13.i3.96132","DOI":"10.5492\/wjccm.v13.i3.96132"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","unstructured":"He CJ Zhu CY Fan HY et al. Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy. Clin Cardiol 2023; 46(12): 1569\u20131577. https:\/\/doi.org\/10.1002\/clc.24156","DOI":"10.1002\/clc.24156"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","unstructured":"Pingitore A Mastorci F Berti S et al. Hypovitaminosis D and low T3 syndrome: a link for therapeutic challenges in patients with acute myocardial infarction. J Clin Med 2021; 10(22): 5267. https:\/\/doi.org\/10.3390\/jcm10225267","DOI":"10.3390\/jcm10225267"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"Shigihara S Shirakabe A Kobayashi N et al. Clinical significance of low-triiodothyronine syndrome in patients requiring non-surgical intensive care - triiodothyronine is a comprehensive prognostic marker for critical patients with cardiovascular disease. Circ Rep 2021; 3(10): 578\u2013588. https:\/\/doi.org\/10.1253\/circrep.CR-21-0040","DOI":"10.1253\/circrep.CR-21-0040"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","unstructured":"Li W Gao R Wang W et al. Low T3 syndrome as a predictor of poor prognosis in peripheral T-cell lymphomas. Clin Transl Oncol 2024; 26(3): 613\u2013622. https:\/\/doi.org\/10.1007\/s12094-023-03280-9","DOI":"10.1007\/s12094-023-03280-9"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","unstructured":"Pan Q Jian Y Zhang Y et al. The association between low T3 syndrome and survival in patients with newly diagnosed multiple myeloma: a retrospective study. Technol Cancer Res Treat 2022; 21: 15330338221094422. https:\/\/doi.org\/10.1177\/15330338221094422","DOI":"10.1177\/15330338221094422"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","unstructured":"Lang H Wan X Ma M et al. Low triiodothyronine syndrome increased the incidence of acute kidney injury after cardiac surgery. Int J Gen Med 2022; 15: 867\u2013876. https:\/\/doi.org\/10.2147\/IJGM.S349993","DOI":"10.2147\/IJGM.S349993"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","unstructured":"Langer MM Bauschen A Guckenbiehl S et al. Evolution of non-thyroidal illness syndrome in acute decompensation of liver cirrhosis and acute-on-chronic liver failure. Front Endocrinol (Lausanne) 2023; 14: 1104388. https:\/\/doi.org\/10.3389\/fendo.2023.1104388","DOI":"10.3389\/fendo.2023.1104388"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","unstructured":"Lado-Abeal J Diaz C Berdine G et al. High prevalence of non-thyroidal illness syndrome in patients at long-term care facilities. Endocrine 2020; 70(2): 348\u2013355. https:\/\/doi.org\/10.1007\/s12020-020-02321-5","DOI":"10.1007\/s12020-020-02321-5"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","unstructured":"Xu C Wen S Xu Z et al. Low T3 syndrome is associated with imbalance of bone turnover biomarker in patients with type 2 diabetes. Diabetes Metab Syndr Obes 2024; 17: 3667\u20133682. https:\/\/doi.org\/10.2147\/DMSO.S472946","DOI":"10.2147\/DMSO.S472946"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","unstructured":"Chubb SA Davis WA Inman Z et al. Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study. Clin Endocrinol (Oxf) 2005; 62(4): 480\u2013486. https:\/\/doi.org\/10.1111\/j.1365-2265.2005.02246.x","DOI":"10.1111\/j.1365-2265.2005.02246.x"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","unstructured":"Han C He X Xia X et al. Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis. PLoS One 2015; 10(8): e0135233. https:\/\/doi.org\/10.1371\/journal.pone.0135233","DOI":"10.1371\/journal.pone.0135233"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","unstructured":"Cho JH Kim HJ Lee JH et al. Poor glycemic control is associated with the risk of subclinical hypothyroidism in patients with type 2 diabetes mellitus. Korean J Intern Med 2016; 31(4): 703\u2013711. https:\/\/doi.org\/10.3904\/kjim.2015.198","DOI":"10.3904\/kjim.2015.198"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"}],"container-title":["Journal of Investigative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589261497357","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10815589261497357","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589261497357","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T13:50:05Z","timestamp":1793886605000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10815589261497357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":42,"alternative-id":["10.1177\/10815589261497357"],"URL":"https:\/\/doi.org\/10.1177\/10815589261497357","relation":{},"ISSN":["1081-5589","1708-8267"],"issn-type":[{"value":"1081-5589","type":"print"},{"value":"1708-8267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"10815589261497357"}}