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Open Access 01-04-2019 | Original Article

Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus

Authors: T. I. de Vries, L. J. Kappelle, Y. van der Graaf, H. W. de Valk, G. J. de Borst, H. M. Nathoe, F. L. J. Visseren, Jan Westerink, on behalf of the SMART study group

Published in: Acta Diabetologica | Issue 4/2019

Abstract

Aim

To evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies.

Methods

We included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model.

Results

In patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95–1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99–1.14)].

Conclusion

There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.

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Vanderpump MPJ (2011) The epidemiology of thyroid disease. Br Med Bull 99:39–51. https://doi.org/10.1093/bmb/ldr030 CrossRefPubMed

Centers for Disease Control and Prevention (2014) National diabetes statistics report: estimates of diabetes and its burden in the United States. https://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html. Accessed 3 Apr 2017

Wang C (2013) The relationship between type 2 diabetes mellitus and related thyroid diseases. J Diabetes Res 2013:390534. https://doi.org/10.1155/2013/390534 CrossRefPubMedPubMedCentral

Han C, He X, Xia X et al (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

Barker JM (2006) Clinical review: Type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening. J Clin Endocrinol Metab 91:1210–1217CrossRefPubMed

Fleiner HF, Bjoro T, Midthjell K et al (2016) Prevalence of thyroid dysfunction in autoimmune and type 2 diabetes: the population-based HUNT study in Norway. J Clin Endocrinol Metab 101:669–677. https://doi.org/10.1210/jc.2015-3235 CrossRefPubMed

Song F, Bao C, Deng M et al (2017) The prevalence and determinants of hypothyroidism in hospitalized patients with type 2 diabetes mellitus. Endocrine 55:179–185. https://doi.org/10.1007/s12020-016-1095-2 CrossRefPubMed

Coller FA, Huggins CB (1927) Effect of hyperthyroidism upon diabetes mellitus: striking improvement in diabetes mellitus from thyroidectomy. Ann Surg 86:877–884CrossRefPubMedPubMedCentral

Dimitriadis G, Baker B, Marsh H et al (1985) Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am J Physiol 248:E593–E601PubMed

10.

Lambadiari V, Mitrou P, Maratou E et al (2011) Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes. Endocrine 39:28–32. https://doi.org/10.1007/s12020-010-9408-3 CrossRefPubMed

11.

Dimitriadis G, Mitrou P, Lambadiari V et al (2006) Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab 91:4930–4937CrossRefPubMed

12.

Verga Falzacappa C, Panacchia L, Bucci B et al (2006) 3,5,3′-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis. J Cell Physiol 206:309–321CrossRefPubMed

13.

Stanicka S, Vondra K, Pelikanova T et al (2005) Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy. Clin Chem Lab Med 43:715–720CrossRefPubMed

14.

Cho JH, Kim HJ, Lee JH et al (2016) Poor glycemic control is associated with the risk of subclinical hypothyroidism in patients with type 2 diabetes mellitus. Korean J Intern Med 31:703–711. https://doi.org/10.3904/kjim.2015.198 CrossRefPubMedPubMedCentral

15.

Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC (2002) The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol 174:121–125CrossRefPubMed

16.

Gu Y, Li H, Bao X et al (2017) The relationship between thyroid function and the prevalence of type 2 diabetes mellitus in euthyroid subjects. J Clin Endocrinol Metab 102:434–442. https://doi.org/10.1210/jc.2016-2965 CrossRefPubMed

17.

Chaker L, Ligthart S, Korevaar TIM et al (2016) Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Med 14:150. https://doi.org/10.1186/s12916-016-0693-4 CrossRefPubMedPubMedCentral

18.

Jun JE, Jee JH, Bae JC et al (2017) Association between changes in thyroid hormones and incident type 2 diabetes: a seven-year longitudinal study. Thyroid 27:29–38. https://doi.org/10.1089/thy.2016.0171 CrossRefPubMed

19.

Jun JE, Jin SM, Jee JH et al (2017) TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects. Endocrine 55:944–953. https://doi.org/10.1007/s12020-016-1221-1 CrossRefPubMed

20.

Simons PC, Algra A, van de Laak MF et al (1999) Second manifestations of ARTerial disease (SMART) study: rationale and design. Eur J Epidemiol 15:773–781CrossRefPubMed

21.

Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral

22.

Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive summary. Cardiol Rev 13:322–327PubMed

23.

Hollowell JG, Staehling NW, Flanders WD et al (2002) Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87:489–499CrossRefPubMed

24.

Fox CS, Pencina MJ, D’Agostino RB et al (2008) Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Arch Intern Med 168:587–592. https://doi.org/10.1001/archinte.168.6.587 CrossRefPubMed

25.

Franssens BT, van der Graaf Y, Kappelle LJ et al (2015) Body weight, metabolic dysfunction, and risk of type 2 diabetes in patients at high risk for cardiovascular events or with manifest cardiovascular disease: a cohort study. Diabetes Care 38:1945–1951. https://doi.org/10.2337/dc15-0684 CrossRefPubMed

26.

Zhang Z (2016) Missing data imputation: focusing on single imputation. Ann Transl Med 4:9CrossRefPubMedPubMedCentral

27.

Wells G, Shea B, O’Connell D et al The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 11 April 2017

28.

Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327:557–560CrossRef

29.

Brockwell SE, Gordon IR (2001) A comparison of statistical methods for meta-analysis. Stat Med 20:825–840. https://doi.org/10.1002/sim.650 CrossRefPubMed

30.

Hage M, Zantout MS, Azar ST (2011) Thyroid disorders and diabetes mellitus. J Thyroid Res. https://doi.org/10.4061/2011/439463 CrossRefPubMedPubMedCentral

31.

Kim WG, Kim WB, Woo G et al (2017) Thyroid stimulating hormone reference range and prevalence of thyroid dysfunction in the Korean population: Korea National Health and nutrition examination survey 2013 to 2015. Endocrinol Metab 32:106–114. https://doi.org/10.3803/EnM.2017.32.1.106 CrossRef

32.

Casula M, Mozzanica F, Scotti L et al (2017) Statin use and risk of new-onset diabetes: a meta-analysis of observational studies. Nutr Metab Cardiovasc Dis 27:396–406. https://doi.org/10.1016/j.numecd.2017.03.001 CrossRefPubMed

33.

Spanakis EK, Golden SH (2013) Race/ethnic difference in diabetes and diabetic complications. Curr Diab Rep 13:814–823. https://doi.org/10.1007/s11892-013-0421-9 CrossRefPubMed

34.

Heymsfield SB, Peterson CM, Thomas DM et al (2016) Why are there race/ethnic differences in adult body mass index-adiposity relationships? A quantitative critical review. Obes Rev 17:262–275. https://doi.org/10.1111/obr.12358 CrossRefPubMed

35.

Bos MM, Smit RA, Trompet S et al (2017) Thyroid signaling, insulin resistance and type 2 diabetes mellitus: a Mendelian randomization study. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2016-2816 (Epub ahead of print) CrossRefPubMed

36.

Lawlor DA, Harbord RM, Sterne JAC et al (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27:1133–1163. https://doi.org/10.1002/sim.3034 CrossRefPubMed

37.

Hansen PS, Brix TH, Sorensen TIA et al (2004) Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins. J Clin Endocrinol Metab 89:1181–1187. https://doi.org/10.1210/jc.2003-031641 CrossRefPubMed

38.

Sandhu MS, Debenham SL, Barroso I, Loos RJF (2008) Mendelian randomisation studies of type 2 diabetes: future prospects. Diabetologia 51:211–213. https://doi.org/10.1007/s00125-007-0903-x CrossRefPubMedPubMedCentral

39.

Iwen KA, Schroder E, Brabant G (2013) Thyroid hormones and the metabolic syndrome. Eur Thyroid J 2:83–92. https://doi.org/10.1159/000351249 CrossRefPubMedPubMedCentral

40.

Gronich N, Deftereos SN, Lavi I et al (2015) Hypothyroidism is a risk factor for new-onset diabetes: a cohort study. Diabetes Care 38:1657–1664. https://doi.org/10.2337/dc14-2515 CrossRefPubMed

41.

Brandt F, Thvilum M, Almind D et al (2013) Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study. PLoS One 8:e66711. https://doi.org/10.1371/journal.pone.0066711 CrossRefPubMedPubMedCentral

42.

Thvilum M, Brandt F, Almind D et al (2013) Type and extent of somatic morbidity before and after the diagnosis of hypothyroidism. a nationwide register study. PLoS One 8:e75789. https://doi.org/10.1371/journal.pone.0075789 CrossRefPubMedPubMedCentral

Title: Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus
Authors: T. I. de Vries
L. J. Kappelle
Y. van der Graaf
H. W. de Valk
G. J. de Borst
H. M. Nathoe
F. L. J. Visseren
Jan Westerink
on behalf of the SMART study group
Publication date: 01-04-2019
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 4/2019
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-018-1231-y

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