Diabetes Metab J.  2019 Dec;43(6):867-878. 10.4093/dmj.2018.0130.

The Relationship between Thyroid Function and Different Obesity Phenotypes in Korean Euthyroid Adults

• Kim JM
• Kim BH
• Lee H
• Kim EH
• Kim M
• Kim JH
• Jeon YK
• Kim SS
• Kim IJ
• Kim YK

• KMID: 2466507
• DOI: http://doi.org/10.4093/dmj.2018.0130

Abstract

BACKGROUND
Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete.
METHODS
This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health.
RESULTS
At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P<0.001) in total study population. However, this significant association no longer remained after adjustment for age, urine iodine concentration, and smoking (P=0.085). After adjustment for confounders, statistically significant association was observed between lower thyroid stimulating hormone (TSH) and MHNO phenotype (P=0.044). In men participants (not women), higher fT4 values were significantly associated with MHNO phenotype (P<0.001). However, no significant association was observed between thyroid function (TSH or fT4) and obesity phenotypes in groups classified by age (cutoff age of 55 years).
CONCLUSION
Although there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.

Keyword

Metabolic syndrome; Obesity; Phenotype; Sex; Thyroid hormones

MeSH Terms

Adipose Tissue
Adult*
Body Mass Index
Cardiovascular Diseases
Humans
Iodine
Korea
Male
Nutrition Surveys
Obesity*
Obesity, Metabolically Benign
Phenotype*
Smoke
Smoking
Thyroid Diseases
Thyroid Gland*
Thyroid Hormones
Thyrotropin
Thyroxine
Iodine
Smoke
Thyroid Hormones
Thyrotropin
Thyroxine

Reference

1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr. International Diabetes Federation Task Force on Epidemiology and Prevention. Hational Heart, Lung, and Blood Institute. American Heart Association. World Heart Federation. International Atherosclerosis Society. International Association for the Study of Obesity. 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; 120:1640–1645. PMID: 19805654.

2. Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome vs Framingham risk score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch Intern Med. 2005; 165:2644–2650. PMID: 16344423.

3. Scuteri A, Najjar SS, Morrell CH, Lakatta EG. Cardiovascular Health Study. The metabolic syndrome in older individuals: prevalence and prediction of cardiovascular events: the Cardiovascular Health Study. Diabetes Care. 2005; 28:882–887. PMID: 15793190.

4. Ford ES. The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis. 2004; 173:309–314. PMID: 15064107.

5. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003; 289:76–79. PMID: 12503980.

6. Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S, Buchan I, Day N, Khaw KT. Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation Into Cancer and Nutrition in Norfolk cohort: a population-based prospective study. Circulation. 2007; 116:2933–2943. PMID: 18071080.

7. Seo MH, Rhee EJ. Metabolic and cardiovascular implications of a metabolically healthy obesity phenotype. Endocrinol Metab (Seoul). 2014; 29:427–434. PMID: 25559571.

8. Kantartzis K, Machann J, Schick F, Rittig K, Machicao F, Fritsche A, Haring HU, Stefan N. Effects of a lifestyle intervention in metabolically benign and malign obesity. Diabetologia. 2011; 54:864–868. PMID: 21174075.

9. Geetha L, Deepa M, Anjana RM, Mohan V. Prevalence and clinical profile of metabolic obesity and phenotypic obesity in Asian Indians. J Diabetes Sci Technol. 2011; 5:439–446. PMID: 21527117.

10. Jung CH, Lee WJ, Song KH. Metabolically healthy obesity: a friend or foe? Korean J Intern Med. 2017; 32:611–621. PMID: 28602062.

11. Arnlov J, Ingelsson E, Sundstrom J, Lind L. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2010; 121:230–236. PMID: 20038741.

12. Jeon MJ, Kim WG, Kwon H, Kim M, Park S, Oh HS, Han M, Kim TY, Shong YK, Kim WB. Excessive iodine intake and thyrotropin reference interval: data from the Korean National Health and Nutrition Examination Survey. Thyroid. 2017; 27:967–972. PMID: 28471294.

13. Kim WG, Kim WB, Woo G, Kim H, Cho Y, Kim TY, Kim SW, Shin MH, Park JW, Park HL, Oh K, Chung JH. 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 (Seoul). 2017; 32:106–114. PMID: 28116874.

14. Bahi L, Garnier A, Fortin D, Serrurier B, Veksler V, Bigard AX, Ventura-Clapier R. Differential effects of thyroid hormones on energy metabolism of rat slow- and fast-twitch muscles. J Cell Physiol. 2005; 203:589–598. PMID: 15605382.

15. Roef GL, Rietzschel ER, Van Daele CM, Taes YE, De Buyzere ML, Gillebert TC, Kaufman JM. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid. 2014; 24:223–231. PMID: 24032604.

16. Bensenor IM, Goulart AC, Molina Mdel C, de Miranda EJ, Santos IS, Lotufo PA. Thyrotropin levels, insulin resistance, and metabolic syndrome: a cross-sectional analysis in the Brazilian longitudinal study of adult health (ELSA-Brasil). Metab Syndr Relat Disord. 2015; 13:362–369. PMID: 26177236.

17. Lin SY, Wang YY, Liu PH, Lai WA, Sheu WH. Lower serum free thyroxine levels are associated with metabolic syndrome in a Chinese population. Metabolism. 2005; 54:1524–1528. PMID: 16253643.

18. 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; 28:180–186. PMID: 23525791.

19. Lee YK, Kim JE, Oh HJ, Park KS, Kim SK, Park SW, Kim MJ, Cho YW. Serum TSH level in healthy Koreans and the association of TSH with serum lipid concentration and metabolic syndrome. Korean J Intern Med. 2011; 26:432–439. PMID: 22205844.

20. Kim BJ, Kim TY, Koh JM, Kim HK, Park JY, Lee KU, Shong YK, Kim WB. Relationship between serum free T4 (FT4) levels and metabolic syndrome (MS) and its components in healthy euthyroid subjects. Clin Endocrinol (Oxf). 2009; 70:152–160. PMID: 18494864.

21. 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; 92:491–496. PMID: 17090642.

22. Lai Y, Wang J, Jiang F, Wang B, Chen Y, Li M, Liu H, Li C, Xue H, Li N, Yu J, Shi L, Bai X, Hou X, Zhu L, Lu L, Wang S, Xing Q, Teng X, Teng W, Shan Z. The relationship between serum thyrotropin and components of metabolic syndrome. Endocr J. 2011; 58:23–30. PMID: 21135510.

23. Amouzegar A, Kazemian E, Abdi H, Mansournia MA, Bakhtiyari M, Hosseini MS, Azizi F. Association between thyroid function and development of different obesity phenotypes in euthyroid adults: a nine-year follow-up. Thyroid. 2018; 28:458–464. PMID: 29620968.

24. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001; 285:2486–2497. PMID: 11368702.

25. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol (Oxf). 2005; 62:487–491. PMID: 15807881.

26. Mantzoros CS, Ozata M, Negrao AB, Suchard MA, Ziotopoulou M, Caglayan S, Elashoff RM, Cogswell RJ, Negro P, Liberty V, Wong ML, Veldhuis J, Ozdemir IC, Gold PW, Flier JS, Licinio J. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab. 2001; 86:3284–3291. PMID: 11443202.

27. Zhai X, Zhang L, Chen L, Lian X, Liu C, Shi B, Shi L, Tong N, Wang S, Weng J, Zhao J, Teng X, Yu X, Lai Y, Wang W, Li C, Mao J, Li Y, Fan C, Li L, Shan Z, Teng W. An age-specific serum thyrotropin reference range for the diagnosis of thyroid diseases in older adults: a cross-sectional survey in China. Thyroid. 2018; 28:1571–1579.

28. Mehran L, Amouzegar A, Bakhtiyari M, Mansournia MA, Rahimabad PK, Tohidi M, Azizi F. Variations in serum free thyroxine concentration within the reference range predicts the incidence of metabolic syndrome in non-obese adults: a cohort study. Thyroid. 2017; 27:886–893. PMID: 28486021.

29. Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report. 2009; 13:1–7.

30. Kuk JL, Ardern CI. Age and sex differences in the clustering of metabolic syndrome factors: association with mortality risk. Diabetes Care. 2010; 33:2457–2461. PMID: 20699434.

31. Geer EB, Shen W. Gender differences in insulin resistance, body composition, and energy balance. Gend Med. 2009; 6(Suppl 1):60–75. PMID: 19318219.

32. Shin JA, Mo EY, Kim ES, Moon SD, Han JH. Association between lower normal free thyroxine concentrations and obesity phenotype in healthy euthyroid subjects. Int J Endocrinol. 2014; 2014:104318. PMID: 24872812.

33. De Pergola G, Ciampolillo A, Paolotti S, Trerotoli P, Giorgino R. Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women. Clin Endocrinol (Oxf). 2007; 67:265–269. PMID: 17547687.

34. Roef G, Lapauw B, Goemaere S, Zmierczak HG, Toye K, Kaufman JM, Taes Y. Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men. Eur J Endocrinol. 2012; 167:719–726. PMID: 22956557.

35. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol. 2010; 316:165–171. PMID: 19540303.