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Published in: BMC Endocrine Disorders 1/2017

Open Access 01-12-2017 | Research article

Thyroid function and metabolic syndrome in the population-based LifeLines cohort study

Authors: Bruce H. R. Wolffenbuttel, Hanneke J. C. M. Wouters, Sandra N. Slagter, Robert P. van Waateringe, Anneke C. Muller Kobold, Jana V. van Vliet-Ostaptchouk, Thera P. Links, Melanie M. van der Klauw

Published in: BMC Endocrine Disorders | Issue 1/2017

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Abstract

Background

The metabolic syndrome (MetS) is a combination of unfavourable health factors which includes abdominal obesity, dyslipidaemia, elevated blood pressure and impaired fasting glucose. Earlier studies have reported a relationship between thyroid function and some MetS components or suggested that serum free thyroxine (FT4) or free triiodothyronine (FT3) levels within the normal range were independently associated with insulin resistance. We assessed how thyroid function relates to MetS prevalence in a large population-based study.

Methods

Data of 26,719 people of western European descent, aged 18–80 years from the Dutch LifeLines Cohort study, all with normal thyroid stimulating hormone (TSH), FT4 and FT3 levels (electrochemiluminescent immunoassay, Roche Modular E170 Analyzer), were available. MetS was defined with the revised National Cholesterol Education Programs Adults Treatment Panel III (NCEP ATP III) criteria. We calculated prevalence of all MetS components according to TSH, FT4 and FT3 quartiles.

Results

At similar TSH levels and age (mean 45 yrs), men had significantly higher levels of FT4, FT3, blood pressure (BP), heart rate, total and LDL-cholesterol, triglycerides (TG), and creatinine, but lower HDL-cholesterol compared to women (all p < 0.001). In total, 11.8% of women and 20.7% of men had MetS. In men, lower FT4 levels were associated with higher prevalence of MetS and all MetS components. In women, lower FT4 quartile was only associated with a higher prevalence of elevated TG, waist circumference, and MetS. However, when corrected for confounding factors like age, BMI, current smoking and alcohol consumption, a significant relationship was found between FT3 and three MetS components in men, and all five components in women. Moreover, the highest quartiles of FT3 and the FT3FT4 ratio predicted a 49% and 67% higher prevalence of MetS in men, and a 62 and 80% higher prevalence in women.

Conclusions

When corrected for possible confounding factors, higher plasma levels of FT3 are associated with several components of the MetS. Only in men, lower FT4 is related to MetS. In the highest FT3 and FT3FT4 quartiles, there is a 50–80% increased risk of having MetS compared to the lowest quartile. Further studies are needed to assess the possible causality of this relationship.
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Literature
1.
go back to reference Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; world heart federation; international atherosclerosis society; and International Association for the Study of obesity. Circulation. 2009;120:1640–5.CrossRefPubMed Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; world heart federation; international atherosclerosis society; and International Association for the Study of obesity. Circulation. 2009;120:1640–5.CrossRefPubMed
3.
go back to reference Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007;92:491–6.CrossRefPubMed Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007;92:491–6.CrossRefPubMed
4.
go back to reference Kim BJ, Kim TY, Koh JM, Kim HK, Park JY, Lee KU, et al. Relationship between serum free T4 (FT4) levels and metabolic syndrome (MS) and its components in healthy euthyroid subjects. Clin Endocrinol. 2009;70:152–60.CrossRef Kim BJ, Kim TY, Koh JM, Kim HK, Park JY, Lee KU, et al. Relationship between serum free T4 (FT4) levels and metabolic syndrome (MS) and its components in healthy euthyroid subjects. Clin Endocrinol. 2009;70:152–60.CrossRef
5.
go back to reference Park SB, Choi HC, Joo NS. The relation of thyroid function to components of the metabolic syndrome in Korean men and women. J Korean Med Sci. 2011;26:540–5.CrossRefPubMedPubMedCentral Park SB, Choi HC, Joo NS. The relation of thyroid function to components of the metabolic syndrome in Korean men and women. J Korean Med Sci. 2011;26:540–5.CrossRefPubMedPubMedCentral
6.
go back to reference Kim HJ, Bae JC, Park HK, Byun DW, Suh K, Yoo MH, et al. Triiodothyronine levels are independently associated with metabolic syndrome in Euthyroid middle-aged subjects. Endocrinol Metab (Seoul). 2016;31:311–9.CrossRef Kim HJ, Bae JC, Park HK, Byun DW, Suh K, Yoo MH, et al. Triiodothyronine levels are independently associated with metabolic syndrome in Euthyroid middle-aged subjects. Endocrinol Metab (Seoul). 2016;31:311–9.CrossRef
7.
go back to reference Park SY, Park SE, Jung SW, Jin HS, Park IB, Ahn SV, et al. Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects. Clin Endocrinol. 2017;87:87–96.CrossRef Park SY, Park SE, Jung SW, Jin HS, Park IB, Ahn SV, et al. Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects. Clin Endocrinol. 2017;87:87–96.CrossRef
8.
go back to reference Slagter SN, van Vliet-Ostaptchouk JV, Vonk JM, Boezen HM, Dullaart RP, Kobold AC, et al. Combined effects of smoking and alcohol on metabolic syndrome: the LifeLines cohort study. PLoS One. 2014;9:e96406.CrossRefPubMedPubMedCentral Slagter SN, van Vliet-Ostaptchouk JV, Vonk JM, Boezen HM, Dullaart RP, Kobold AC, et al. Combined effects of smoking and alcohol on metabolic syndrome: the LifeLines cohort study. PLoS One. 2014;9:e96406.CrossRefPubMedPubMedCentral
9.
go back to reference Stolk RP, Rosmalen JG, Postma DS, de Boer RA, Navis G, Slaets JP, et al. Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study. Eur J Epidemiol. 2008;23:67–74.CrossRefPubMed Stolk RP, Rosmalen JG, Postma DS, de Boer RA, Navis G, Slaets JP, et al. Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study. Eur J Epidemiol. 2008;23:67–74.CrossRefPubMed
10.
go back to reference Scholtens S, Smidt N, Swertz MA, Bakker SJ, Dotinga A, Vonk JM, et al. Cohort profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol. 2015;44:1172–80.CrossRefPubMed Scholtens S, Smidt N, Swertz MA, Bakker SJ, Dotinga A, Vonk JM, et al. Cohort profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol. 2015;44:1172–80.CrossRefPubMed
11.
go back to reference Schubert CC, Boustani M, Callahan CM, Perkins AJ, Carney CP, Fox C, et al. Comorbidity profile of dementia patients in primary care: are they sicker? J Am Geriatr Soc. 2006;54:104–9.CrossRefPubMed Schubert CC, Boustani M, Callahan CM, Perkins AJ, Carney CP, Fox C, et al. Comorbidity profile of dementia patients in primary care: are they sicker? J Am Geriatr Soc. 2006;54:104–9.CrossRefPubMed
12.
go back to reference Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines cohort study. Thyroid. 2013;23:1066–73.CrossRefPubMedPubMedCentral Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines cohort study. Thyroid. 2013;23:1066–73.CrossRefPubMedPubMedCentral
13.
go back to reference American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–9.CrossRef American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–9.CrossRef
14.
go back to reference Lee K. Gender-specific relationships between alcohol drinking patterns and metabolic syndrome: the Korea National Health and nutrition examination survey 2008. Public Health Nutr. 2012;15:1917–24.CrossRefPubMed Lee K. Gender-specific relationships between alcohol drinking patterns and metabolic syndrome: the Korea National Health and nutrition examination survey 2008. Public Health Nutr. 2012;15:1917–24.CrossRefPubMed
15.
go back to reference Marchi KC, Muniz JJ, Tirapelli CR. Hypertension and chronic ethanol consumption: what do we know after a century of study? World J Cardiol. 2014;6:283–94.PubMedPubMedCentral Marchi KC, Muniz JJ, Tirapelli CR. Hypertension and chronic ethanol consumption: what do we know after a century of study? World J Cardiol. 2014;6:283–94.PubMedPubMedCentral
16.
17.
go back to reference Lee YJ, Woo SY, Ahn JH, Cho S, Kim SR. Health-related quality of life in adults with metabolic syndrome: the Korea national health and nutrition examination survey, 2007-2008. Ann Nutr Metab. 2012;61:275–80.CrossRefPubMed Lee YJ, Woo SY, Ahn JH, Cho S, Kim SR. Health-related quality of life in adults with metabolic syndrome: the Korea national health and nutrition examination survey, 2007-2008. Ann Nutr Metab. 2012;61:275–80.CrossRefPubMed
18.
go back to reference van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K, Foco L, et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.CrossRefPubMedPubMedCentral van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K, Foco L, et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.CrossRefPubMedPubMedCentral
19.
go back to reference Slagter SN, van Vliet-Ostaptchouk JV, van Beek AP, Keers JC, Lutgers HL, van der Klauw MM, et al. Health-related quality of life in relation to obesity grade, type 2 diabetes, metabolic syndrome and inflammation. PloS one 2015;10:e0140599. Slagter SN, van Vliet-Ostaptchouk JV, van Beek AP, Keers JC, Lutgers HL, van der Klauw MM, et al. Health-related quality of life in relation to obesity grade, type 2 diabetes, metabolic syndrome and inflammation. PloS one 2015;10:e0140599.
20.
go back to reference Slagter SN, van Waateringe RP, van Beek AP, van der Klauw MM, Wolffenbuttel BHR, van Vliet-Ostaptchouk JV. Sex, BMI and age differences in metabolic syndrome: the Dutch Lifelines cohort study. Endocr Connect. 2017;6:278–88.CrossRefPubMedPubMedCentral Slagter SN, van Waateringe RP, van Beek AP, van der Klauw MM, Wolffenbuttel BHR, van Vliet-Ostaptchouk JV. Sex, BMI and age differences in metabolic syndrome: the Dutch Lifelines cohort study. Endocr Connect. 2017;6:278–88.CrossRefPubMedPubMedCentral
21.
go back to reference Kim HJ, Bae JC, Park HK, Byun DW, Suh K, Yoo MH, et al. Association of triiodothyronine levels with future development of metabolic syndrome in euthyroid middle-aged subjects: a 6-year retrospective longitudinal study. Eur J Endocrinol. 2017;176:441–50.CrossRefPubMed Kim HJ, Bae JC, Park HK, Byun DW, Suh K, Yoo MH, et al. Association of triiodothyronine levels with future development of metabolic syndrome in euthyroid middle-aged subjects: a 6-year retrospective longitudinal study. Eur J Endocrinol. 2017;176:441–50.CrossRefPubMed
22.
go back to reference Ferrannini E, Iervasi G, Cobb J, Ndreu R, Nannipieri M. Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis. Am J Physiol Endocrinol Metab. 2017;312:E429–E36.CrossRefPubMed Ferrannini E, Iervasi G, Cobb J, Ndreu R, Nannipieri M. Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis. Am J Physiol Endocrinol Metab. 2017;312:E429–E36.CrossRefPubMed
23.
go back to reference Oliveira RM. Role of type 2 deiodinase in hypothalamic control of feeding behavior. J Endocrinology, Diabetes & Obesity. 2014;2:1048. Oliveira RM. Role of type 2 deiodinase in hypothalamic control of feeding behavior. J Endocrinology, Diabetes & Obesity. 2014;2:1048.
24.
go back to reference Bianco AC, Silva JE. Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest. 1987;79:295–300.CrossRefPubMedPubMedCentral Bianco AC, Silva JE. Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest. 1987;79:295–300.CrossRefPubMedPubMedCentral
25.
go back to reference Silva JE. The thermogenic effect of thyroid hormone and its clinical implications. Ann Intern Med. 2003;139:205–13.CrossRefPubMed Silva JE. The thermogenic effect of thyroid hormone and its clinical implications. Ann Intern Med. 2003;139:205–13.CrossRefPubMed
26.
go back to reference Silvestri E, Schiavo L, Lombardi A, Goglia F. Thyroid hormones as molecular determinants of thermogenesis. Acta Physiol Scand. 2005;184:265–83.CrossRefPubMed Silvestri E, Schiavo L, Lombardi A, Goglia F. Thyroid hormones as molecular determinants of thermogenesis. Acta Physiol Scand. 2005;184:265–83.CrossRefPubMed
27.
go back to reference Lombardi A, de Lange P, Silvestri E, Busiello RA, Lanni A, Goglia F, et al. 3,5-Diiodo-L-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement. Am J Physiol Endocrinol Metab. 2009;296:E497–502.CrossRefPubMed Lombardi A, de Lange P, Silvestri E, Busiello RA, Lanni A, Goglia F, et al. 3,5-Diiodo-L-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement. Am J Physiol Endocrinol Metab. 2009;296:E497–502.CrossRefPubMed
28.
go back to reference St-Onge MP, Grandner MA, Brown D, Conroy MB, Jean-Louis G, Coons M, et al. Sleep duration and quality: impact on lifestyle behaviors and cardiometabolic health: a scientific statement from the American Heart Association. Circulation. 2016;134:e367–e86.CrossRefPubMedPubMedCentral St-Onge MP, Grandner MA, Brown D, Conroy MB, Jean-Louis G, Coons M, et al. Sleep duration and quality: impact on lifestyle behaviors and cardiometabolic health: a scientific statement from the American Heart Association. Circulation. 2016;134:e367–e86.CrossRefPubMedPubMedCentral
30.
go back to reference Park HT, Cho GJ, Ahn KH, Shin JH, Hong SC, Kim T, et al. Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women. Maturitas. 2009;62:301–5.CrossRefPubMed Park HT, Cho GJ, Ahn KH, Shin JH, Hong SC, Kim T, et al. Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women. Maturitas. 2009;62:301–5.CrossRefPubMed
31.
go back to reference Garduno-Garcia Jde J, Alvirde-Garcia U, Lopez-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, et al. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol. 2010;163:273–8.CrossRefPubMed Garduno-Garcia Jde J, Alvirde-Garcia U, Lopez-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, et al. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol. 2010;163:273–8.CrossRefPubMed
32.
go back to reference Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, et al. A high normal TSH is associated with the metabolic syndrome. Clin Endocrinol. 2010;72:696–701.CrossRef Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, et al. A high normal TSH is associated with the metabolic syndrome. Clin Endocrinol. 2010;72:696–701.CrossRef
33.
go back to reference Tarcin O, Abanonu GB, Yazici D, Tarcin O. Association of metabolic syndrome parameters with TT3 and FT3/FT4 ratio in obese Turkish population. Metab Syndr Relat Disord. 2012;10:137–42.CrossRefPubMed Tarcin O, Abanonu GB, Yazici D, Tarcin O. Association of metabolic syndrome parameters with TT3 and FT3/FT4 ratio in obese Turkish population. Metab Syndr Relat Disord. 2012;10:137–42.CrossRefPubMed
34.
go back to reference Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic I, et al. Thyroid function and prevalent and incident metabolic syndrome in older adults: the health, ageing and body composition study. Clin Endocrinol. 2012;76:911–8.CrossRef Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic I, et al. Thyroid function and prevalent and incident metabolic syndrome in older adults: the health, ageing and body composition study. Clin Endocrinol. 2012;76:911–8.CrossRef
35.
go back to reference Oh JY, Sung YA, Lee HJ. Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in euthyroid young women. Korean J Intern Med. 2013;28:180–6.CrossRefPubMedPubMedCentral Oh JY, Sung YA, Lee HJ. Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in euthyroid young women. Korean J Intern Med. 2013;28:180–6.CrossRefPubMedPubMedCentral
36.
go back to reference Roef GL, Rietzschel ER, Van Daele CM, Taes YE, De Buyzere ML, Gillebert TC, et al. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid. 2014;24:223–31.CrossRefPubMedPubMedCentral Roef GL, Rietzschel ER, Van Daele CM, Taes YE, De Buyzere ML, Gillebert TC, et al. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid. 2014;24:223–31.CrossRefPubMedPubMedCentral
37.
go back to reference Mehran L, Amouzegar A, Tohidi M, Moayedi M, Azizi F. Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects. Thyroid. 2014;24:1566–74.CrossRefPubMed Mehran L, Amouzegar A, Tohidi M, Moayedi M, Azizi F. Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects. Thyroid. 2014;24:1566–74.CrossRefPubMed
38.
go back to reference Minami Y, Takaya R, Takitani K, Ishiro M, Okasora K, Niegawa T, et al. Association of thyroid hormones with obesity and metabolic syndrome in Japanese children. J Clin Biochem Nutr. 2015;57:121–8.CrossRefPubMedPubMedCentral Minami Y, Takaya R, Takitani K, Ishiro M, Okasora K, Niegawa T, et al. Association of thyroid hormones with obesity and metabolic syndrome in Japanese children. J Clin Biochem Nutr. 2015;57:121–8.CrossRefPubMedPubMedCentral
39.
go back to reference Laclaustra M, Hurtado-Roca Y, Sendin M, Leon M, Ledesma M, Andres E, et al. Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on Spanish men. Nutr Metab Cardiovasc Dis. 2015;25:1095–103.CrossRefPubMed Laclaustra M, Hurtado-Roca Y, Sendin M, Leon M, Ledesma M, Andres E, et al. Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on Spanish men. Nutr Metab Cardiovasc Dis. 2015;25:1095–103.CrossRefPubMed
Metadata
Title
Thyroid function and metabolic syndrome in the population-based LifeLines cohort study
Authors
Bruce H. R. Wolffenbuttel
Hanneke J. C. M. Wouters
Sandra N. Slagter
Robert P. van Waateringe
Anneke C. Muller Kobold
Jana V. van Vliet-Ostaptchouk
Thera P. Links
Melanie M. van der Klauw
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2017
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-017-0215-1

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