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Subclinical Hypothyroidism and Type 2 Diabetes: A Systematic Review and Meta-Analysis
Open accessAbstract
BACKGROUND: Abundant evidence suggests an association between subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM), but small sample sizes and inconclusive data in the literature complicate this assertion. OBJECTIVE: We measured the prevalence of SCH in T2DM population, and investigated whether T2DM increase the risk of SCH and whether SCH was associated with diabetic complications. METHODS: We conducted a meta-analysis using PubMed, EMBASE, Web of Science, Wan Fang, CNKI and VIP databases for literature search. We obtained studies published between January 1, 1980 to December 1, 2014. The studies were selected to evaluate the prevalence of SCH in T2DM subjects, compare the prevalence of SCH in T2DM subjects with those non-diabetics, and investigate whether diabetic complications were more prevalent in SCH than those who were euthyroid. Fixed and random effects meta-analysis models were used, and the outcome was presented as a pooled prevalence with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. RESULTS: Through literature search, 36 articles met the inclusion criteria and these articles contained a total of 61 studies. Funnel plots and Egger's tests showed no publication bias in our studies, except for the pooled prevalence of SCH in T2DM (P = 0.08) and OR for SCH in T2DM (P = 0.04). Trim and fill method was used to correct the results and five potential missing data were replaced respectively. The adjusted pooled prevalence of SCH in T2DM patients was 10.2%, meanwhile, T2DM was associated with a 1.93-fold increase in risk of SCH (95% CI: 1.66, 2.24). Furthermore, SCH might affect the development of diabetic complications with an overall OR of 1.74 (95% CI: 1.34, 2.28) for diabetic nephropathy, 1.42 (95% CI: 1.21, 1.67) for diabetic retinopathy, 1.85 (95% CI: 1.35, 2.54) for peripheral arterial disease, and 1.87 (95% CI: 1.06, 3.28) for diabetic peripheral neuropathy. CONCLUSIONS: T2DM patients are more likely to have SCH when compared with healthy population and SCH may be associated with increased diabetic complications. It is necessary to screen thyroid function in patients with T2DM, and appropriate individualized treatments in addition to thyroid function test should be given to T2DM patients with SCH as well.
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“Moreover, SCH might favor diabetic complications with an OR of 1.74 (nephropathy), 1.42 (retinopathy), 1.85 (peripheral arterial disease), and 1.87 (peripheral neuropathy) (103).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [103]
In the citing paper
“Finally, the presence of hypothyroidism negatively impacts glucose and lipid metabolism possibly favoring the onset of insulin resistance and hypercholesterolemia which may, at least in part, be reverted by replacement therapy [9, 10].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [9]
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Wang, X., Wang, H., Li, Q., Wang, P., Xing, Y., Zhang, F., Li, J., & Shan, Z. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac417 · Cited by 20
Thyroid status in patients with Type 2 diabetes attending a Tertiary Care Hospital in Eastern India
Ghosh, S., Pramanik, S., Mukhopadhyay, P., Bhattacharjee, R., Mukherjee, B., Mondal, S., Ghosh, I., Bari, R., & Chowdhury, S. (2018) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_572_17 · Cited by 21
“Results from previous meta-analysis[10] reported SCH might affect the development of diabetic complications with an overall odds ratio of 1.”
MethodResultHan, C., He, X., Xia, X., Guo, J., Liu, A., Liu, X., Wang, X., Li, C., Peng, S., Zhao, W., et al. (2019) · Thyroid · doi:10.1089/thy.2018.0065 · Cited by 21
“It has been shown that thyroid disorders are more prevalent in women (1,13), and in order to be aligned with the clinical scenario, human thyroid tissue was obtained from female patients.”
Kong, X., Wang, J., Gao, G., Tan, M., Ding, B., Li, H., & Ma, J. (2019) · Endocrine Research · doi:10.1080/07435800.2019.1690504 · Cited by 20
Relationship between Thyroid Function and Kidney Function in Patients with Type 2 Diabetes
Zhang, Y., Wang, Y., Tao, X. J., Li, Q., Li, F. F., Lee, K., Li, D. M., & Ma, J. (2018) · International Journal of Endocrinology · doi:10.1155/2018/1871530 · Cited by 19
“Despite overt thyroid disease being uncommon in type 2 diabetic patients, there is an increase in subclinical hypothyroidism in these patients when compared with healthy population [13], but it is not known if the change in eGFR and CKD in these patients with T2D is related to thyroid function, especially in patients…”
BackgroundSui, M., Yu, Y., Zhang, H., Di, H., Liu, C., & Fan, Y. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00494 · Cited by 21
Metabolic and Functional Cross Talk Between the Thyroid and Liver
Chng, C., Goh, G., & Yen, P. M. (2025) · Thyroid · doi:10.1089/thy.2025.0178 · Cited by 26
“67 Additionally, a progressive decline in thyroid function, even within the euthyroid range, is associated with an increased risk of developing T2DM, and this relationship is observed regardless of gender or thyroid autoimmunity.”
Huang, X., Zhang, X., Zhou, X., Han, X., Fu, Z., Li, Y., & Ji, L. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s271328 · Cited by 18
Liu, Y., Li, X., Zhu, Y., Liu, J., & Liu, S. (2021) · Journal of Food Biochemistry · doi:10.1111/jfbc.13753 · Cited by 18
Metabolic Syndrome and Subclinical Hypothyroidism: A Type 2 Diabetes-Dependent Association
Bermúdez, V., Salazar, J. J., Áñez, R., Rojas, M., Estrella, V., Ordoñez, M., Chacín, M., Hernández-Lalinde, J., Arias, V., Cabrera, M., et al. (2018) · Journal of Thyroid Research · doi:10.1155/2018/8251076 · Cited by 18
“Similarly, this association does not seem to be limited to early T2DM stages, but to also be related to the apparition of chronic complications such as diabetic nephropathy [26, 27].”
BackgroundThe Impact of Hypothyroidism on Diabetes Mellitus and Its Complications: A Comprehensive Review
Vemula, S. L., Aramadaka, S., Mannam, R., Narayanan, R. S., Bansal, A., Yanamaladoddi, V. R., & Sarvepalli, S. S. (2023) · Cureus · doi:10.7759/cureus.40447 · Cited by 17
“(2015) [5] Meta-analysis 13,740 Analysis of 36 studies from various databases from January 1, 1980, to December 1, 2014, of T2DM and hypothyroid patients Hypothyroidism increases the risk of developing diabetic nephropathy and diabetic peripheral neuropathy.”
BackgroundMethodInfluentialReddy, N., Pradeep, T. V. S., Tirupati, S., Sarathi, V., & Kumar, D. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.05.005 · Cited by 16
Iwakura, H., Takagi, T., Inaba, H., Doi, A., Ueda, Y., Uraki, S., Takeshima, K., Furukawa, Y., Ishibashi, T., Morita, S., et al. (2023) · BMC Endocrine Disorders · doi:10.1186/s12902-023-01393-4 · Cited by 16
“The prevalence of thyroid dysfunction has been widely reported to be high in patients with type 2 diabetes [2, 7, 8, 11, 13, 16, 19], but others argue that the incidence of thyroid dysfunction is not dissimilar to that of the general population [15, 20–23].”
BackgroundCorrelation between Subclinical Hypothyroidism and Metabolic Syndrome: A Retrospective Study
Alsulami, S., Baig, M., Albeladi, A., Alyoubi, S., Alsubaie, S. A., Albeladi, S. A., Ghamri, K. A., Alraiqi, A., Alyoubi, S., & Almutairi, W. A. (2023) · Saudi Journal of Medicine and Medical Sciences · doi:10.4103/sjmms.sjmms_225_22 · Cited by 17
“[12] Therefore, difference is expected, as both age and diabetes are associated with an increased risk of SCH; the latter possibly because insulin influences thyrotropin‑releasing hormone and TSH.[25] The prevalence was also lower than reported in the study published by Al Eidan et al., and this can be attributed to t…”
BackgroundResultInfluentialHe, Q., Zeng, Z., Zhao, M., Ruan, B., & Chen, P. (2023) · Scientific Reports · doi:10.1038/s41598-023-40752-y · Cited by 18
“We speculated that when FT4 was at a normal low level, it would have an impact on lipid metabolism, serum protein metabolism, oxidative stress and serum Ca level, and accelerate the occurrence of DPN. Patients with T2DM are more likely to develop SCH and hypoFT4 than healthy individuals 24,25 .”
BackgroundNicolini, G., Casini, G., Posarelli, C., Amato, R., Lulli, M., Balzan, S., & Forini, F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137364 · Cited by 17
Lai, Y., Wang, H., Xia, X., Wang, Z., Fan, C., Wang, H., Zhang, H., Ding, S., Teng, W., & Shan, Z. (2016) · Medicine · doi:10.1097/md.0000000000005001 · Cited by 16
TSH oscillations in young patients with type 1 diabetes may be due to glycemic variability
Bellastella, G., Maiorino, M. I., Scappaticcio, L., Casciano, O., Petrizzo, M., Caputo, M., Paglionico, V. A., Giugliano, D., & Esposito, K. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0752-5 · Cited by 17
Xie, J., Wang, X., Zhang, Y., Li, H., Xu, Y., & Zheng, D. (2019) · BMC Endocrine Disorders · doi:10.1186/s12902-019-0405-0 · Cited by 16
Diabetes and subclinical hypothyroidism on heart rate variability
Hoshi, R. A., Santos, I. S., Dantas, E. M., Andreão, R. V., Mill, J. G., Duncan, B. B., Schmidt, M. I., Lotufo, P. A., & Benseñor, I. M. (2020) · European Journal of Clinical Investigation · doi:10.1111/eci.13349 · Cited by 15
Wolide, A. D., Zawdie, B., Alemayehu, T., & Tadesse, S. (2016) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2016.12.041 · Cited by 15
Sun, M., Yu, L., Xue, Z., Ren, L., Liu, X., Gang, X., & Wang, G. (2024) · Scientific Reports · doi:10.1038/s41598-024-70673-3 · Cited by 16
“Several meta-analyses have shown that low FT4 levels are related to T2DM, DN, DR, and DPN, yet no study has examined the role of the diabetes duration in this process 22,35,36 .”
BackgroundTudor, R. M., Garrahy, A., Woods, C. P., Crowley, R. K., Tormey, W. P., Smith, D., Hatunic, M., & Thompson, C. J. (2019) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-019-02082-9 · Cited by 14
“worse metabolic control, including dyslipidemia [11], higher rates of microvascular complications [12], and increased rates of coronary artery disease in type 2 diabetes [23].”
BackgroundWang, L., Chen, T., Yu, J., Yuan, H., Deng, X., & Zhao, Z. (2020) · International Journal of Endocrinology · doi:10.1155/2020/2172781 · Cited by 14
“*yroid dysfunction and subclinical dysfunction were also associated with T2D and its complications [9].”
BackgroundShould we be screening for thyroid dysfunction in patients with type 2 diabetes mellitus?
Ward, R. J., Heald, A. H., Ogunmekan, S., Fryer, A. A., & Duff, C. J. (2018) · British Journal of General Practice · doi:10.3399/bjgp18x694793 · Cited by 14
L-T4 therapy in the presence of pharmacological interferents
Benvenga, S. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.607446 · Cited by 13
Li, Z., Wang, S., Zhao, H., Yan, P., Yuan, H., Zhao, M., Wan, R., Yu, G., & Wang, L. (2023) · Scientific Reports · doi:10.1038/s41598-023-28536-w · Cited by 13
Fang, T., Deng, X., Wang, J., Han, F., Liu, X., Liu, Y., Sun, B., & Chen, L. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1288284 · Cited by 13
A Review of Diabetic Peripheral Neuropathy Management given Recent Guidelines Updates.
Hamed, E. S., & Monem, M. A. (2018) · Archives of General Internal Medicine · doi:10.4066/2591-7951.1000060 · Cited by 14
“On the other hand, The thyroid stimulating hormone (TSH) was higher in a Chinese population with DPN, and in another systematic analysis, subclinical hypothyroidism was associated with more diabetic complications [16,17].”
ResultLee, Y. K., Lee, D.-E., Hwangbo, Y., Lee, Y. J., Kim, H. C., & Lee, E. K. (2020) · Thyroid · doi:10.1089/thy.2019.0709 · Cited by 15
“Second, hypothyroidism is a well-established predisposing factor for atherosclerotic cardiovascular disease and is also associated with the onset of stroke, congestive heart failure, diabetes mellitus, and diabetic complications (10–13 , 36).”
Aleksić, Ž., Aleksić, A., & Đorđević, B. (2022) · Timocki medicinski glasnik · doi:10.5937/tmg2201011a · Cited by 14
Derkach, K. V., Pechalnova, A. S., Sorokoumov, V. N., Zorina, I. I., Morina, I. Y., Chernenko, E. E., Didenko, E. A., Romanova, I. V., & Shpakov, A. O. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020703 · Cited by 12
“The combination of T2DM and various forms of hypothyroidism is a risk factor for the development of diabetic nephropathy, diabetic retinopathy, a wide range of cardiovascular diseases, and diabetic neuropathy [8].”
Aldossari, K. K., Al-Ghamdi, S. H., Alzahrani, J. M., Jammah, A. A., Alanazi, B. G., Albriek, A. Z., & Alanazi, M. A. (2019) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.22983 · Cited by 12
de Vries, T. I., de Valk, H. W., van der Graaf, Y., de Borst, G. J., Cramer, M. J., Kappelle, L. J., Visseren, F. L. J., & Westerink, J. (2019) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2019.107880 · Cited by 10
Wang, Y., Lu, J., Ni, J., Wang, M., Shen, Y., Lu, W., Zhu, W., Bao, Y., & Zhou, J. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3639 · Cited by 11
“Evidence from a meta‐analysis suggested that both clinical hypothyroidism and subclinical hypothyroidism may be associated with an increased risk of DR.(27,28) However, current information regarding the association between thyroid hormones in normal ranges and DR is relatively scarce and conflicting.”
Gao, J., & Liu, J. (2024) · BMC Endocrine Disorders · doi:10.1186/s12902-024-01699-x · Cited by 11
“…results reported by Han et al. This study, which included 61 meta-studies, concluded that the prevalence of subclinical hypothyroidism was higher in T2DM patients, and that subclinical hypothyroidism increased the prevalence of diabetic nephropathy (odds ratio [OR] 1.74, 95% CI: 1.34–2.28) [ 19].”
ResultInfluentialWang, C., Dai, X., Zhang, D., Liu, Z., & Huang, Q. (2018) · BioMed Research International · doi:10.1155/2018/4764030 · Cited by 12
Early menarche is independently associated with subclinical hypothyroidism: a cross-sectional study
Kotopouli, M., Stratigou, T., Antonakos, G., Christodoulatos, G. S., Karampela, Ι., & Dalamaga, Μ. (2019) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0079 · Cited by 11
Hussain, T., Barik, B. S., Nayak, A., Das, S., Khadanga, U. K., Yadav, V., & Pati, S. (2019) · Thyroid Research and Practice · doi:10.4103/trp.trp_48_18 · Cited by 11
Association between the use of allopurinol and risk of increased thyroid-stimulating hormone level
Choi, W., Yang, Y.-S., Chang, D. J., Chung, Y. W., Kim, H., Ko, S. J., Yoo, S., Oh, J. S., Kang, D. Y., Yang, H., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-98954-1 · Cited by 11
Chen, H., Wu, J., & Lyu, R. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1282 · Cited by 14
“11 Moreover, increasing evidence have demonstrated that patients with T2DM may affect their thyroid function to varying degrees through multiple pathways, and thyroid dysfunction also has adverse effects on metabolism, which accelerates the clinical process of T2DM.”
BackgroundStoica, R. A., Drăgana, N., Ancuceanu, R., Geicu, O. I., Guja, C., Stoian, A. P., Gheorghe, D., Staden, R. S., Serafinceanu, C., Costache, A., et al. (2022) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2022.100299 · Cited by 9
“This increases the risk of T2DM onset in this population, especially if low access to healthcare is a problem [35,36].”
BackgroundDecreased circulating levels of ANGPTL8 in Graves’ disease patients
Li, H., Xu, M., Zhao, L., Xia, H., Li, Y., Hong, X., Deng, X., Yuan, J., Ding, Y., Guo, C. Y., et al. (2019) · HORMONES · doi:10.1007/s42000-019-00095-8 · Cited by 9
Human immunodeficiency virus, diabetes mellitus and thyroid abnormalities: Should we be screening?
Pillay, S., Pillay, D., Deepak, S., & Pillay, R. (2020) · Southern African Journal of HIV Medicine · doi:10.4102/sajhivmed.v21i1.1116 · Cited by 8
Alterations of the gut microbiota in type 2 diabetics with or without subclinical hypothyroidism
Lv, Y., Liu, R., Jia, H., Sun, X., Gong, Y., Ma, L., Qiu, W., & Wang, X. (2023) · PeerJ · doi:10.7717/peerj.15193 · Cited by 8
“Compare to T2D patients, T2D_SCH patients are more likely to suffer from diabetes complications such as diabetic nephropathy ( Han et al., 2015 ; Mansournia et al., 2017 ).”
Result
Metadata
- Authors
- Han, C., He, X., Xia, X., Li, Y., Shi, X., Shan, Z., & Teng, W.
- Affiliations
- First Hospital of China Medical University (CN)
- Corresponding author
- Shi, Xiaoguang
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-08-13
- Volume
- 10
- Issue
- 8
- Pages
- e0135233
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4535849
- OpenAlex
- W1766479548
- Cited by
- 258
- References
- 65
- Citations by year
- 2026: 10 · 2025: 31 · 2024: 25 · 2023: 36 · 2022: 23 · 2021: 29 · 2020: 31 · 2019: 25 · 2018: 24 · 2017: 10 · 2016: 11 · 2015: 3
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- China Medical University
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- subclinical hypothyroidism, type 2 diabetes, prevalence, diabetes complications, diabetic nephropathy, diabetic retinopathy, peripheral arterial disease, diabetic peripheral neuropathy, thyroid function
- MeSH terms
- Diabetes Mellitus, Type 2, Diabetic Nephropathies, Diabetic Neuropathies, Diabetic Retinopathy, Humans, Hypothyroidism, Risk Factors, Prevalence, Odds Ratio
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