Subscribe to RSS
DOI: 10.1055/s-0030-1267997
© Georg Thieme Verlag KG Stuttgart · New York
T3/rT3-Ratio is Associated with Insulin Resistance Independent of TSH
Publication History
received 29.06.2010
accepted 20.10.2010
Publication Date:
22 November 2010 (online)

Abstract
Thyroid dysfunction has been shown to be associated with insulin resistance (IR). This may involve peripheral thyroid hormone metabolism, which is assumed to be reflected by the ratio triiodothyronine/reverse triiodothyronine (T3/rT3-ratio). To explore a potential association between the T3/rT3-ratio and IR we investigated pairs which differed in IR, but were matched by sex, age, body mass index (BMI), and thyroid stimulating hormone (TSH). For this purpose, matched pair analyses were embedded into a cross sectional study group. 22 pairs were matched from either the first or the third tertile of HOMA%S of a cohort of 353 euthyroid subjects with normal glucose metabolism who did not take any medication. The T3/rT3-ratio was compared in the matched pairs. The T3/rT3-ratio was significantly increased in the insulin resistant subjects compared to their insulin sensitive partners (8.78±0.47 vs. 7.33±0.33, p=0.019). Furthermore the T3/rT3-ratio was lower in men compared to women (p for the within-subject effect=0.046) both in the insulin sensitive and the insulin resistant subjects. Here we show that the T3/rT3-ratio, which is supposed to reflect the tissue thyroid hormone metabolism, is significantly increased in insulin resistant subjects. This further supports a link between thyroid function and IR.
Key words
diabetes mellitus type 2 - insulin resistance - thyroid function
References
- 1
Ronnemaa T, Laakso M, Pyorala K, Kallio V, Puukka P.
High fasting plasma insulin is an indicator of coronary heart disease in non-insulin-dependent
diabetic patients and nondiabetic subjects.
Arterioscler Thromb.
1991;
11
80-90
Reference Ris Wihthout Link
- 2
Skarfors ET, Selinus KI, Lithell HO.
Risk factors for developing non-insulin dependent diabetes: a 10 year follow up of
men in Uppsala.
BMJ.
1991;
303
755-760
Reference Ris Wihthout Link
- 3
Zimmet P, Dowse G, Bennett P.
Hyperinsulinaemia is a predictor of non-insulin-dependent diabetes mellitus.
Diabetes Metab.
1991;
17
101-108
Reference Ris Wihthout Link
- 4
Faggiano A, Pivonello R, Spiezia S, De Martino MC, Filippella M, Di Somma C, Lombardi G, Colao A.
Cardiovascular risk factors and common carotid artery caliber and stiffness in patients
with Cushing's disease during active disease and 1 year after disease remission.
J Clin Endocrinol Metab.
2003;
88
2527-2533
Reference Ris Wihthout Link
- 5
Seidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R.
Visceral fat accumulation in men is positively associated with insulin, glucose, and
C-peptide levels, but negatively with testosterone levels.
Metabolism.
1990;
39
897-901
Reference Ris Wihthout Link
- 6
Simon D, Charles MA, Nahoul K, Orssaud G, Kremski J, Hully V, Joubert E, Papoz L, Eschwege E.
Association between plasma total testosterone and cardiovascular risk factors in healthy
adult men: The Telecom Study.
J Clin Endocrinol Metab.
1997;
82
682-685
Reference Ris Wihthout Link
- 7
Ohguni S, Notsu K, Kato Y.
Correlation of plasma free thyroxine levels with insulin sensitivity and metabolic
clearance rate of insulin in patients with hyperthyroid Graves’ disease.
Intern Med.
1995;
34
339-341
Reference Ris Wihthout Link
- 8
Cavallo-Perin P, Bruno A, Boine L, Cassader M, Lenti G, Pagano G.
Insulin resistance in Graves’ disease: a quantitative in-vivo evaluation.
Eur J Clin Invest.
1988;
18
607-613
Reference Ris Wihthout Link
- 9
Dimitriadis G, Baker B, Marsh H, Mandarino L, Rizza R, Bergman R, Haymond M, Gerich J.
Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in
humans.
Am J Physiol.
1985;
248
E593-E601
Reference Ris Wihthout Link
- 10
Tene C, Zarate A, Basurto L, Islas S, Revilla C, Ochoa R, Galvan R, Santos P.
Correction of insulin resistance in methimazole-treated patients with Graves disease.
Rev Invest Clin.
2001;
53
531-535
Reference Ris Wihthout Link
- 11
Yavuz DG, Yuksel M, Deyneli O, Ozen Y, Aydin H, Akalin S.
Association of serum paraoxonase activity with insulin sensitivity and oxidative stress
in hyperthyroid and TSH-suppressed nodular goitre patients.
Clin Endocrinol (Oxf).
2004;
61
515-521
Reference Ris Wihthout Link
- 12
Heemstra KA, Smit JW, Eustatia-Rutten CF, Heijboer AC, Frolich M, Romijn JA, Corssmit EP.
Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism
and the effects of restoration of euthyroidism, a randomised controlled trial.
Clin Endocrinol (Oxf).
2006;
65
737-744
Reference Ris Wihthout Link
- 13
Rochon C, Tauveron I, Dejax C, Benoit P, Capitan P, Fabricio A, Berry C, Champredon C, Thieblot P, Grizard J.
Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism.
Clin Sci (Lond).
2003;
104
7-15
Reference Ris Wihthout Link
- 14
Stanicka S, Vondra K, Pelikanova T, Vlcek P, Hill M, Zamrazil V.
Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid
hormone replacement therapy.
Clin Chem Lab Med.
2005;
43
715-720
Reference Ris Wihthout Link
- 15
Owecki M, Nikisch E, Sowinski J.
Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in totally
thyroidectomized patients.
Acta Clin Belg.
2006;
61
69-73
Reference Ris Wihthout Link
- 16
Harris PE, Walker M, Clark F, Home PD, Alberti KG.
Forearm muscle metabolism in primary hypothyroidism.
Eur J Clin Invest.
1993;
23
585-588
Reference Ris Wihthout Link
- 17
Jackson IM, Prentice CR, McKiddie MT.
The effect of hypothyroidism on glucose tolerance and insulin metabolism.
J Endocrinol.
1970;
47
257-258
Reference Ris Wihthout Link
- 18
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
Reference Ris Wihthout Link
- 19
Fernandez-Real JM, Lopez-Bermejo A, Castro A, Casamitjana R, Ricart W.
Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent
vasodilation in healthy euthyroid subjects.
J Clin Endocrinol Metab.
2006;
91
3337-3343
Reference Ris Wihthout Link
- 20
Park HT, Cho GJ, Ahn KH, Shin JH, Hong SC, Kim T, Hur JY, Kim YT, Lee KW, Kim SH.
Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal
women.
Maturitas.
2009;
62
301-305
Reference Ris Wihthout Link
- 21
Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, Schöfl C, Pfeiffer AF, Möhlig M.
A high normal TSH is associated with the metabolic syndrome.
Clin Endocrinol (Oxf).
2010;
72
696-701
Reference Ris Wihthout Link
- 22
Mueller A, Schöfl C, Dittrich R, Cupisti S, Oppelt PG, Schild RL, Beckmann MW, Haberle L.
Thyroid-stimulating hormone is associated with insulin resistance independently of
body mass index and age in women with polycystic ovary syndrome.
Hum Reprod.
2009;
24
2924-2930
Reference Ris Wihthout Link
- 23
Bakker SJ, ter Maaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO.
The relationship between thyrotropin and low density lipoprotein cholesterol is modified
by insulin sensitivity in healthy euthyroid subjects.
J Clin Endocrinol Metab.
2001;
86
1206-1211
Reference Ris Wihthout Link
- 24
Ortega E, Koska J, Pannacciulli N, Bunt JC, Krakoff J.
Free triiodothyronine plasma concentrations are positively associated with insulin
secretion in euthyroid individuals.
Eur J Endocrinol.
2008;
158
217-221
Reference Ris Wihthout Link
- 25
Köhrle J.
Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination.
Best Pract Res Clin Endocrinol Metab.
2007;
21
173-191
Reference Ris Wihthout Link
- 26
Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeold A, Bianco AC.
Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling.
Endocr Rev.
2008;
29
898-938
Reference Ris Wihthout Link
- 27
Peeters RP, van der Deure WM, Visser TJ.
Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor
and the iodothyronine deiodinases.
Eur J Endocrinol.
2006;
155
655-662
Reference Ris Wihthout Link
- 28
Matthaei S, Stumvoll M, Kellerer M, Häring HU.
Pathophysiology and pharmacological treatment of insulin resistance.
Endocr Rev.
2000;
21
585-618
Reference Ris Wihthout Link
- 29
Fischer A, Fisher E, Möhlig M, Schulze M, Hoffmann K, Weickert MO, Schueler R, Osterhoff M, Pfeiffer AF, Boeing H, Spranger J.
KCNJ11 E23K affects diabetes risk and is associated with the disposition index: results
of two independent German cohorts.
Diabetes Care.
2008;
31
87-89
Reference Ris Wihthout Link
- 30
Marassi MP, Fortunato RS, da Silva AC, Pereira VS, Carvalho DP, Rosenthal D, da Costa VM.
Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase activity
in pre-pubertal and adult rats.
J Endocrinol.
2007;
192
121-130
Reference Ris Wihthout Link
- 31
Lisboa PC, Cabanelas AP, Curty FH, Oliveira KJ, Ortiga-Carvalho TM, Moura EG, Nascimento-Saba CC, Rosenthal D, Pazos-Moura CC.
Modulation of type 2 iodothyronine deiodinase activity in rat thyroid gland.
Horm Metab Res.
2007;
39
538-541
Reference Ris Wihthout Link
- 32
Fisher DA.
Physiological variations in thyroid hormones: physiological and pathophysiological
considerations.
Clinical Chemistry.
1996;
42
135-139
Reference Ris Wihthout Link
- 33
Köhrle J.
Thyroid hormone metabolism and action.
Z Arztl Fortbild Qualitatssich.
2004;
98
(S 05)
17-24
Reference Ris Wihthout Link
- 34
Chidakel A, Mentuccia D, Celi FS.
Peripheral metabolism of thyroid hormone and glucose homeostasis.
Thyroid.
2005;
15
899-903
Reference Ris Wihthout Link
- 35
Shimizu Y, Shimazu T.
Thyroid hormone augments GLUT4 expression and insulin-sensitive glucose transport
system in differentiating rat brown adipocytes in culture.
J Vet Med Sci.
2002;
64
677-681
Reference Ris Wihthout Link
- 36
Torrance CJ, Devente JE, Jones JP, Dohm GL.
Effects of thyroid hormone on GLUT4 glucose transporter gene expression and NIDDM
in rats.
Endocrinology.
1997;
138
1204-1214
Reference Ris Wihthout Link
- 37
Silva JE, Larsen PR.
Hormonal regulation of iodothyronine 5′-deiodinase in rat brown adipose tissue.
American Journal of Physiology.
1986;
251
E639-E643
Reference Ris Wihthout Link
- 38
Mills I, Barge RM, Silva JE, Larsen PR.
Insulin stimulation of iodothyronine 5′-deiodinase in rat brown adipocytes.
Biochem Biophys Res Commun.
1987;
143
81-86
Reference Ris Wihthout Link
- 39
Heemstra KA, Soeters MR, Fliers E, Serlie MJ, Burggraaf J, van Doorn MB, van der Klaauw AA, Romijn JA, Smit JW, Corssmit EP, Visser TJ.
Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and
fasting.
J Clin Endocrinol Metab.
2009;
94
2144-2150
Reference Ris Wihthout Link
- 40
Sato K, Robbins J.
Thyroid hormone metabolism in primary cultured rat hepatocytes. Effects of glucose,
glucagon, and insulin.
J Clin Invest.
1981;
68
475-483
Reference Ris Wihthout Link
- 41
Wacholder S, Silverman DT, McLaughlin JK, Mandel JS.
Selection of controls in case-control studies. III. Design options.
Am J Epidemiol.
1992;
135
1042-1050
Reference Ris Wihthout Link
- 42
Wallace TM, Levy JC, Matthews DR.
Use and abuse of HOMA modeling.
Diabetes Care.
2004;
27
1487-1495
Reference Ris Wihthout Link
Correspondence
M. MöhligMD
Department of Endocrinology
Diabetes and Nutrition
Charité-University Medicine
Berlin
Campus Benjamin Franklin
Hindenburgdamm 30
12200 Berlin
Germany
Phone: +49/30/8445 2114
Fax: +49/30/8445 4204
Email: matthias.moehlig@charite.de