Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Roya Pasandideh, Seyed M. Hosseini*, Gholamreza Veghari and Sharebeh Hezarkhani

DOI: 10.2174/1871530319666191105123005

DownloadDownload PDF Flyer Cite As
The Effects of 8 Weeks of Levothyroxine Replacement Treatment on Metabolic and Anthropometric Indices of Insulin Resistance in Hypothyroid Patients

Page: [745 - 752] Pages: 8

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: Insulin resistance (IR) is an independent cardiovascular risk factor. IR predisposes to metabolic syndrome and diabetes. Meanwhile, little evidence exists about the effect of levothyroxine replacement treatment (LRT) on IR in hypothyroid patients.

Objective: To investigate metabolic and anthropometric indices of IR in hypothyroid patients before and after 8 weeks of LRT.

Methods: This pre-post study evaluated the 8 weeks outcomes of LRT on 66 patients with recently diagnosed hypothyroidism. Outcome measures included body mass index (BMI), waist circumferences (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), body fat percent (BF%), free thyroxin (FT4), triglyceride (TG), low density lipoprotein (LDL), fasting plasma levels of glucose (FPG) and insulin. Sex- specific cut offs of two metabolic indices i.e. the triglyceride-glucose (TyG) and the homeostasis model assessment (HOMA) were used for IR diagnosis. The changes in TyG and HOMA were also compared after LRT.

Results: Participants were overt and subclinical hypothyroidism 71% and 29%, respectively. After LRT the mean values of the following anthropometric indices significantly decreased: weight (79.61 vs. 78.64), BMI (29.53 vs. 29.2), WC (98.25 vs. 97.39) and BF% (35.34 vs. 34.95). After LRT the HOMA and TyG had no significant changes relative to their initial values. Also, IR that was determined on the basis of these metabolic indices more commonly observed in participants.

Conclusion: Despite decreasing some anthropometric indices, the diagnosis of IR based on metabolic indices increased following 8 weeks LRT in hypothyroid cases.

Keywords: Insulin resistance, hypothyroidism, anthropometric indices, TyG, HOMA, levothyroxine.

Graphical Abstract

[1]
Biondi, B.; Kahaly, G.J.; Robertson, R.P. Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders. Endocr. Rev., 2019, 40(3), 789-824.
[http://dx.doi.org/10.1210/er.2018-00163] [PMID: 30649221]
[2]
Martinez, B.; Ortiz, R.M. Thyroid hormone regulation and insulin resistance: Insights from animals naturally adapted to fasting. Physiology (Bethesda), 2017, 32(2), 141-151.
[3]
Gyawali, P.; Takanche, J.S.; Shrestha, R.K.; Bhattarai, P.; Khanal, K.; Risal, P.; Koju, R. Pattern of thyroid dysfunction in patients with metabolic syndrome and its relationship with components of metabolic syndrome. Diabetes Metab. J., 2015, 39(1), 66-73.
[http://dx.doi.org/10.4093/dmj.2015.39.1.66] [PMID: 25729715]
[4]
Vondra, K.; Vrbikova, J.; Dvorakova, K. Thyroid gland diseases in adult patients with diabetes mellitus. Minerva Endocrinol., 2005, 30(4), 217-236.
[PMID: 16319810]
[5]
Grassetto, G.; Rubello, D. Thyroid disorders and diabetes mellitus. Minerva Med., 2008, 99(3), 263-267.
[PMID: 18497724]
[6]
Jamshir, M.; Fayaz, M.; Mirbehbahani, N.; Hosseini, S.M. TyG index and insulin resistance in beta-thalassemia. Int. J. Diabetes Dev. Ctries., 2015, 35(3), 529-534.
[http://dx.doi.org/10.1007/s13410-015-0418-9]
[7]
Borai, A.; Livingstone, C.; Kaddam, I.; Ferns, G. Selection of the appropriate method for the assessment of insulin resistance. BMC Med. Res. Methodol., 2011, 11, 158-168.
[http://dx.doi.org/10.1186/1471-2288-11-158] [PMID: 22112229]
[8]
Vanesa, N.; Svjetlana, L.Z.; Jasmin, S. Anthropometric Correlation with Metabolic Syndrome in Sarajevo Population. Endocr. Metab. Immune Disord. Drug Targets, 2016, 16(2), 113-119.
[http://dx.doi.org/10.2174/1871530316666160208150135] [PMID: 26853885]
[9]
Corrêa, M.M.; Thumé, E.; De Oliveira, E.R.; Tomasi, E. Performance of the waist-to-height ratio in identifying obesity and predicting non-communicable diseases in the elderly population: A systematic literature review. Arch. Gerontol. Geriatr., 2016, 65, 174-182.
[http://dx.doi.org/10.1016/j.archger.2016.03.021] [PMID: 27061665]
[10]
Yang, H.; Xin, Z.; Feng, J.P.; Yang, J.K. Waist-to-height ratio is better than body mass index and waist circumference as a screening criterion for metabolic syndrome in Han Chinese adults. Medicine (Baltimore), 2017, 96(39)e8192
[http://dx.doi.org/10.1097/MD.0000000000008192] [PMID: 28953680]
[11]
Cheng, Y.H.; Tsao, Y.C.; Tzeng, I.S.; Chuang, H.H.; Li, W.C.; Tung, T.H.; Chen, J.Y. Body mass index and waist circumference are better predictors of insulin resistance than total body fat percentage in middle-aged and elderly Taiwanese. Medicine (Baltimore), 2017, 96(39)e8126
[http://dx.doi.org/10.1097/MD.0000000000008126] [PMID: 28953643]
[12]
Lam, B.C.; Koh, G.C.; Chen, C.; Wong, M.T. Comparison of Body Mass Index (BMI), Body Adiposity Index (BAI), Waist Circumference (WC), Waist-To-Hip Ratio (WHR) and Waist-To-Height Ratio (WHtR) as predictors of cardiovascular disease risk factors in an adult population in Singapore. PLoS One, 2015, 16,10(4)e0122985
[13]
Chen, S.; Chen, Y.; Liu, X.; Li, M.; Wu, B.; Li, Y.; Liang, Y.; Shao, X.; Holthöfer, H.; Zou, H. Insulin resistance and metabolic syndrome in normal-weight individuals. Endocrine, 2014, 46(3), 496-504.
[http://dx.doi.org/10.1007/s12020-013-0079-8] [PMID: 24190050]
[14]
Qureshi, N.K.; Hossain, T.; Hassan, M.I.; Akter, N.; Rahman, M.M.; Sultana, M.M.; Ashrafuzzaman, S.M.; Latif, Z.A. Neck Circumference as a Marker of Overweight and Obesity and Cutoff Values for Bangladeshi Adults. Indian J. Endocrinol. Metab., 2017, 21(6), 803-808.
[http://dx.doi.org/10.4103/ijem.IJEM_196_17] [PMID: 29285438]
[15]
Fantin, F.; Comellato, G.; Rossi, A.P.; Grison, E.; Zoico, E.; Mazzali, G.; Zamboni, M. Relationship between neck circumference, insulin resistance and arterial stiffness in overweight and obese subjects. Eur. J. Prev. Cardiol., 2017, 24(14), 1532-1540.
[http://dx.doi.org/10.1177/2047487317721655] [PMID: 28728486]
[16]
Androutsos, O.; Grammatikaki, E.; Moschonis, G.; Roma-Giannikou, E.; Chrousos, G.P.; Manios, Y.; Kanaka-Gantenbein, C. Neck circumference: a useful screening tool of cardiovascular risk in children. Pediatr. Obes., 2012, 7(3), 187-195.
[http://dx.doi.org/10.1111/j.2047-6310.2012.00052.x] [PMID: 22505226]
[17]
Gregory, A. Brent and Anthony, P.; Weetman. Hypothyroidism and Thyroiditis.Williams Textbook of Endocrinology; Melmed, S.; Polonsky, K.S.; Larsen, P.R; Kronenberg, H.M., Ed.; Elsevier: Philadelphia, PA, 2016.
[18]
Hosseini, S.M. Triglyceride-glucose (TyG) index computation and cut-off. Acta Endo, 2015, 11, 130-131.
[http://dx.doi.org/10.4183/aeb.2015.130]
[19]
Esteghamati, A.; Ashraf, H.; Esteghamati, A.R.; Meysamie, A.; Khalilzadeh, O.; Nakhjavani, M.; Abbasi, M. Optimal threshold of homeostasis model assessment for insulin resistance in an Iranian population: the implication of metabolic syndrome to detect insulin resistance. Diabetes Res. Clin. Pract., 2009, 84(3), 279-287.
[http://dx.doi.org/10.1016/j.diabres.2009.03.005] [PMID: 19359063]
[20]
Zadeh-Vakili, A.; Tehrani, F.R.; Hosseinpanah, F. Waist circumference and insulin resistance: a community based cross sectional study on reproductive aged Iranian women. Diabetol. Metab. Syndr., 2011, 3(3), 18.
[http://dx.doi.org/10.1186/1758-5996-3-18] [PMID: 21831271]
[21]
Lee, S.H.; Han, K.; Yang, H.K.; Kim, H.S.; Cho, J.H.; Kwon, H.S.; Park, Y.M.; Cha, B.Y.; Yoon, K.H. A novel criterion for identifying metabolically obese but normal weight individuals using the product of triglycerides and glucose. Nutr. Diabetes, 2015, 27(5), 49.
[http://dx.doi.org/10.1038/nutd.2014.46]
[22]
Mehdavi, E.; Hezarkhani, S.; Hosseini, S.M. Insulin resistance in hypothyroid patients using HOMA and triglyceride glucose indices. Majallah-i Danishgah-i Ulum-i Pizishki-i Gurgan, 2018, 20(1), 96-101. [Article in Persian].
[23]
Waist circumference and waist-hip ratio: report of a WHO expert consultation; Geneva, 2008.
[24]
Deurenberg, P.; Weststrate, J.A.; Seidell, J.C. Body mass index as a measure of body fatness: age- and sex-specific prediction formulas. Br. J. Nutr., 1991, 65(2), 105-114.
[http://dx.doi.org/10.1079/BJN19910073] [PMID: 2043597]
[25]
Sirigiri, S.; Vaikkakara, S.; Sachan, A.; Srinivasarao, P.V.; Epuri, S.; Anantarapu, S.; Mukka, A.; Chokkapu, S.R.; Venkatanarasu, A.; Poojari, R. Correction of hypothyroidism leads to change in lean body mass without altering insulin resistance. Eur. Thyroid J., 2016, 5(4), 247-252.
[http://dx.doi.org/10.1159/000448889] [PMID: 28101489]
[26]
Samuels, M.H.; Kolobova, I.; Smeraglio, A.; Peters, D.; Purnell, J.Q.; Schuff, K.G. Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition. Thyroid, 2016, 26(3), 347-355.
[http://dx.doi.org/10.1089/thy.2015.0345] [PMID: 26700485]
[27]
Kim, M.K.; Kwon, H.S.; Baek, K.H.; Lee, J.H.; Park, W.C.; Sohn, H.S.; Lee, K.W.; Song, K.H. Effects of thyroid hormone on A1C and glycated albumin levels in nondiabetic subjects with overt hypothyroidism. Diabetes Care, 2010, 33(12), 2546-2548.
[http://dx.doi.org/10.2337/dc10-0988] [PMID: 20823345]
[28]
Deyneli, O.; Akpınar, I.N.; Meriçliler, O.S.; Gözü, H.; Yıldız, M.E.; Akalın, N.S. Effects of levothyroxine treatment on insulin sensitivity, endothelial function and risk factors of atherosclerosis in hypothyroid women. Ann. Endocrinol. (Paris), 2014, 75(4), 220-226.
[http://dx.doi.org/10.1016/j.ando.2014.06.002] [PMID: 25145560]
[29]
Nada, A.M. Effect of treatment of overt hypothyroidism on insulin resistance. World J. Diabetes, 2013, 4(4), 157-161.
[30]
Sengupta, S.; Jaseem, T.; Ambalavanan, J.; Hegde, A. Homeostatic model assessment-insulin resistance (HOMA-IR 2) in mild subclinical hypothyroid subjects. Indian J. Clin. Biochem., 2018, 33(2), 214-217.
[http://dx.doi.org/10.1007/s12291-017-0647-4] [PMID: 29651214]
[31]
Singh, B.M.; Goswami, B.; Mallika, V. Association between insulin resistance and hypothyroidism in females attending a tertiary care hospital. Indian J. Clin. Biochem., 2010, 25(2), 141-145.
[http://dx.doi.org/10.1007/s12291-010-0026-x] [PMID: 23105900]
[32]
Kar, K.; Sinha, S. Variations of adipokines and insulin resistance in primary hypothyroidism. J. Clin. Diagn. Res., 2017, 11(8), BC07-BC09.
[http://dx.doi.org/10.7860/JCDR/2017/26666.10345] [PMID: 28969110]
[33]
Samuels, M.H.; Kolobova, I.; Antosik, M.; Niederhausen, M. Purnell,J.Thyroid function variation in the normal range, energy expenditure, and body composition in L-T4-Treated subjects. J. Clin. Endocrinol. Metab., 2017, 102(7), 2533-2542.
[34]
Paolo, D. V.; Elena, C.; Ragab, G. A.; Paolo, L.; Paul, J. D.; Sandra, I.; Jens, Z. P. Role of Thyroid Hormones in Insulin Resistance and Diabetes. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization) 2015. 15, 86-93.
[35]
Peeters, R.P.; Visser, T.J. Metabolism of Thyroid Hormone. [Updated 2017 Jan 1]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc. 2000.Available from: . https://www.ncbi.nlm.nih.gov/books/NBK285545/
[36]
Hennessey, J.V.; Espaillat, R. Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy. Int. J. Clin. Pract., 2018, 72(2), 13062.
[http://dx.doi.org/10.1111/ijcp.13062] [PMID: 29381251]
[37]
Roti, E.; Minelli, R.; Salvi, M. Thyroid hormone metabolism in obesity. Int. J. Obes. Relat. Metab. Disord., 2000, 24(2)(Suppl. 2), S113-S115.
[http://dx.doi.org/10.1038/sj.ijo.0801293] [PMID: 10997624]
[38]
Younis, I.R.; Ahmed, M.A.; Burman, K.D.; Soldin, O.P.; Jonklaas, J. Stable Isotope Pharmacokinetic Studies Provide Insight into Effects of Age, Sex, and Weight on Levothyroxine Metabolism. Thyroid, 2018, 28(1), 41-49.
[http://dx.doi.org/10.1089/thy.2017.0380] [PMID: 29212434]
[39]
Hoermann, R.; Cheung, A.S.; Milne, M.; Grossmann, M. Hypothalamic-pituitary-thyroid axis set point alterations are associated with body composition in androgen-deprived men. J. Endocr. Soc., 2017, 1(7), 874-885.
[40]
Handisurya, A.; Pacini, G.; Tura, A.; Gessl, A.; Kautzky-Willer, A. Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH). Clin. Endocrinol. (Oxf.), 2008, 69(6), 963-969.
[http://dx.doi.org/10.1111/j.1365-2265.2008.03280.x] [PMID: 18429948]
[41]
Rajput, R.; Pathak, V. The effect of daily versus weekly levothyroxine replacement on thyroid function test in hypothyroid patients at a tertiary care centre in haryana. Eur. Thyroid J., 2017, 6(5), 250-254.
[http://dx.doi.org/10.1159/000477348] [PMID: 29071237]
[42]
Michaelsson, L.F.; la Cour, J.L.; Medici, B.B.; Watt, T.; Faber, J.; Nygaard, B. Levothyroxine/liothyronine combination therapy and quality of life: Is it all about weight loss? Eur. Thyroid J., 2018, 7(5), 243-250.
[http://dx.doi.org/10.1159/000490383] [PMID: 30374427]
[43]
Singh, R.; Tandon, A.; Gupta, S.K.; Saroja, K. Optimal levothyroxine replacement adequately improves symptoms of hypothyroidism; Residual symptoms need further evaluation for other than hypothyroidism causation. Indian J. Endocrinol. Metab., 2017, 21(6), 830-835.
[http://dx.doi.org/10.4103/ijem.IJEM_165_17] [PMID: 29285444]
[44]
Anantarapu, S.; Vaikkakara, S.; Sachan, A.; Phaneendra, B.V.; Suchitra, M.M.; Reddy, A.P.; Epuri, S.; Mukka, A.; Vemvakam, D. Effects of thyroid hormone replacement on glycated hemoglobin levels in non diabetic subjects with overt hypothyroidism. Arch. Endocrinol. Metab., 2015, 59(6), 495-500.
[http://dx.doi.org/10.1590/2359-3997000000065] [PMID: 26421666]
[45]
Stangierski, A.; Ruchała, M.; Krauze, T.; Moczko, J.; Guzik, P. Treatment of severe thyroid function disorders and changes in body composition. Endokrynol. Pol., 2016, 67(4), 359-366.
[PMID: 26884294]
[46]
Pearce, E.N. Thyroid hormone and obesity. Curr. Opin. Endocrinol. Diabetes Obes., 2012, 19(5), 408-413.
[http://dx.doi.org/10.1097/MED.0b013e328355cd6c] [PMID: 22931855]
[47]
Pinkney, J.H.; Goodrick, S.J.; Katz, J.; Johnson, A.B.; Lightman, S.L.; Coppack, S.W.; Mohamed-Ali, V. Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects. Clin. Endocrinol. (Oxf.), 1998, 49(5), 583-588.
[http://dx.doi.org/10.1046/j.1365-2265.1998.00573.x] [PMID: 10197072]