, Volume 42, Issue 1, pp 139–145 | Cite as

Insulin sensitivity modifies the relationship between thyroid function and lipid profile in euthyroid type 1 diabetic patients

  • Tomislav Bulum
  • Branko Kolarić
  • Lea Duvnjak
Original Article


It has been suggested that association between hypothyroidism with dyslipidemia might be present already at the stage of normal thyroid function through altered insulin sensitivity. We analyzed the role of insulin sensitivity as a mediator of thyroid-induced lipid changes in euthyroid type 1 diabetic patients. Study included 304 patients with type 1 diabetes and normal thyroid function. Insulin sensitivity was measured with estimated glucose disposal rate calculated using the equation: eGDR = 24.31 − (12.22 × WHR) − (3.29 × HT) − (0.57 × HbA1c); WHR = waist-to-hip ratio, HT = hypertension. TSH, FT4, FT3, and serum lipids were measured. Correlations and multiple linear regressions analysis were performed to identify relationships between thyroid status and serum lipid parameters after stratifying patients in quartiles of eGDR. After adjustment for age, sex, BMI, duration of diabetes and insulin dose TSH, FT3, and FT4 was not significantly associated with serum lipids in all patients, independently of level of insulin sensitivity. However, after stratifying patients for the degree of insulin sensitivity in subjects in the lowest quartile of insulin sensitivity TSH was independently associated with LDL cholesterol (β = 0.210, p = 0.02). The independent relation of eGDR with TSH and LDL cholesterol suggests that the influence of thyroid function on lipid metabolism might extend into euthyroid range through altered insulin sensitivity.


Type 1 diabetes Insulin sensitivity Thyroid function Serum lipids Estimated glucose disposal rate 


Conflicts of interest



  1. 1.
    Peppa M., Betsi G., Dimitriadis G. Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J. Lipids (2011). doi: 10.1155/2011/575840
  2. 2.
    B. Kim, Thyroid hormone as a determinant of energy expenditure and the basal metabolic state. Thyroid 18, 141–144 (2008)PubMedCrossRefGoogle Scholar
  3. 3.
    X. Zhu, S.Y. Cheng, New insights into regulation of lipid metabolism by thyroid hormone. Curr. Opin. Endocrinol. Diabetes Obes. 17, 408–413 (2010)PubMedCrossRefGoogle Scholar
  4. 4.
    A.E. Hak, H.A. Pols, T.J. Visser, H.A. Drexhage, A. Hofman, J.C. Witteman, Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann. Intern. Med. 132, 270–278 (2000)PubMedGoogle Scholar
  5. 5.
    L.H. Duntas, Thyroid disease and lipids. Thyroid 12, 287–293 (2002)PubMedCrossRefGoogle Scholar
  6. 6.
    S. Miura, H. Iitaka, H. Yoshimura, S. Kitahama, N. Fukasawa, Y. Kawakami, S. Sakurai, M. Urabe, Y. Sakatsume, K. Ito, J. Ishii, Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy. Intern. Med. 33, 413–417 (1994)PubMedCrossRefGoogle Scholar
  7. 7.
    G. Brenta, G. Berg, P. Arias, V. Zago, M. Schnitman, M. Luz Muzzio, I. Sinay, L. Schreier, Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in subclinical hypothyroidism: response to L-T4 treatment. Thyroid 17, 453–460 (2007)PubMedCrossRefGoogle Scholar
  8. 8.
    G. Brenta, G. Berg, V. Zago, M. Luz Muzzio, M. Schnitman, I. Sinay, P. Arias, L. Schreier, Proatherogenic mechanisms in subclinical hypothyroidism: hepatic lipase activity in relation to the VLDL remnant IDL. Thyroid 18, 1233–1236 (2008)PubMedCrossRefGoogle Scholar
  9. 9.
    A. Maratou, D.J. Hadjidakis, A. Kollias, K. Tsegka, M. Peppa, M. Alevizaki, P. Mitrou, V. Lambadiari, E. Boutati, D. Nikzas, N. Tountas, T. Economopoulos, S.A. Raptis, G. Dimitriadis, Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur. J. Endocrinol. 160, 785–790 (2009)PubMedCrossRefGoogle Scholar
  10. 10.
    C. Rochon, I. Tauveron, C. Dejax, P. Benoit, P. Capittan, A. Fabricio, C. Berry, C. Champredon, P. Thieblot, J. Grizard, Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin. Sci. 104, 7–15 (2003)PubMedCrossRefGoogle Scholar
  11. 11.
    F. Amati, J.J. Dube, F. Stefanovic-Racic, F.G. Toledo, B.H. Goodpaster, Improvements in insulin sensitivity are blunted by subclinical hypothyroidism. Med. Sci. Sports Exerc. 41, 265–269 (2009)PubMedGoogle Scholar
  12. 12.
    Peppa M., Koliaki C., Nikolopoulos P., Raptis S.A. Skeletal muscle insulin resistance in endocrine disease. J. Biomed. Biotechnol. (2010). doi: 10.1155/2010/527850
  13. 13.
    R.H. Eckel, S.M. Grundy, P.Z. Zimmet, The metabolic syndrome. Lancet 365, 1415–1428 (2005)PubMedCrossRefGoogle Scholar
  14. 14.
    H.K. Kumar, R.K. Yadav, J. Prajapati, C.V. Reddy, M. Raghunath, K.D. Modi, Association between thyroid hormones, insulin resistance, and metabolic syndrome. Saudi Med. J. 30, 179–183 (2009)Google Scholar
  15. 15.
    A. Roos, S.J. Bakker, T.P. Links, R.O. Gans, B.H. Wolffenbuttel, Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J. Clin. Endocrinol. Metab. 92, 491–496 (2007)PubMedCrossRefGoogle Scholar
  16. 16.
    R.A. DeFronzo, R. Hendler, D. Simonson, Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes 31, 795–801 (1982)PubMedGoogle Scholar
  17. 17.
    F.I. Martin, J.L. Hopper, The relationship of acute insulin sensitivity to the progression of vascular disease in long-term type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30, 149–153 (1987)PubMedCrossRefGoogle Scholar
  18. 18.
    J. Yip, M.B. Mattock, A. Morocutti, M. Sethi, R. Trevisan, G. Viberti, Insulin resistance in insulin-dependent diabetic patients with microalbuminuria. Lancet 342, 883–887 (1993)PubMedCrossRefGoogle Scholar
  19. 19.
    E.S. Kilpatrick, A.S. Rigby, S.L. Atkin, Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes. Double diabetes in the Diabetes Control and Complications Trial. Diabetes Care 30, 707–712 (2007)PubMedCrossRefGoogle Scholar
  20. 20.
    T.M. Davis, D.G. Bruce, W.A. Davis, Prevalence and prognostic implications of the metabolic syndrome in community-based patients with type 1 diabetes: The Fremantle Diabetes Study. Diab. Res. Clin. Prac. 78, 412–417 (2007)CrossRefGoogle Scholar
  21. 21.
    T. Bulum, B. Kolarić, L. Duvnjak, M. Duvnjak, Nonalcoholic fatty liver disease markers are associated with insulin resistance in type 1 diabetes. Dig. Dis. Sci. 56, 3655–3663 (2011)PubMedCrossRefGoogle Scholar
  22. 22.
    K.V. Williams, J.R. Erbey, D. Becker, S. Arsianian, T.J. Orchard, Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 49, 626–632 (2000)PubMedCrossRefGoogle Scholar
  23. 23.
    E. Bruckert, P. Giral, R. Chadarevian, G. Turpin, Low free-thyroxine levels are a risk factor for subclinical atherosclerosis in euthyroid hyperlipidemic patients. J. Cardiovasc. Risk 6, 327–331 (1999)PubMedGoogle Scholar
  24. 24.
    B.O. Asvold, L.J. Vatten, T.I. Nilsen, T. Bjoro, The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur. J. Endocrinol. 156, 181–186 (2007)PubMedCrossRefGoogle Scholar
  25. 25.
    G.J. Canaris, N.R. Manowitz, G. Mayor, E.C. Ridgway, The Colorado thyroid disease prevalence study. Arch. Intern. Med. 160, 526–534 (2000)PubMedCrossRefGoogle Scholar
  26. 26.
    S.J. Bakker, J.C. Ter Maaten, C. Popp-Snijder, J.P. Slaets, R.J. Heine, R.O. Gans, The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J. Clin. Endocrinol. Metab. 86, 1206–1211 (2001)PubMedCrossRefGoogle Scholar
  27. 27.
    S.A. Chubb, W.A. Davis, T.M. Davis, Interactions among thyroid function, insulin sensitivity, and serum lipid concentrations: The Fremantle Diabetes Study. J. Clin. Endocrinol. Metab. 90, 5317–5320 (2005)PubMedCrossRefGoogle Scholar
  28. 28.
    J.M. Fernandez-Real, A. Lopez-Bermejo, A. Castro, R. Casamitjana, W. Ricart, Thyroid function in intrinsically linked to insulin sensitivity and endothelium-dependent vasodilatation in healthy euthyroid subjects. J. Clin. Endocrinol. Metab. 91, 3337–3343 (2006)PubMedCrossRefGoogle Scholar
  29. 29.
    L.H. Duntas, J. Orgiazzi, G. Brabant, The interface between thyroid and diabetes mellitus. Clin. Endocrinol. 75, 1–9 (2011)CrossRefGoogle Scholar
  30. 30.
    T. Tzotzas, G.E. Krassas, T. Konstantinidis, M. Bougoulia, Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid 10, 803–808 (2000)PubMedCrossRefGoogle Scholar
  31. 31.
    H.N. Ginsberg, Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels. Diabetes 45, S27–S30 (1996)PubMedGoogle Scholar
  32. 32.
    B.V. Howard, Insulin resistance and lipid metabolism. Am. J. Cardiol. 84, 28J–32J (1999)PubMedCrossRefGoogle Scholar
  33. 33.
    N.F. Galeano, R. Milne, Y.L. Marcel, M.T. Walsh, E. Levy, T.D. Ngu’yen, A. Gleeson, Y. Arad, L. Witte, M. Al-Haideri, S.C. Rumsey, R.J. Deckelbaum, Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size. J. Biol. Chem. 269, 511–519 (1994)PubMedGoogle Scholar
  34. 34.
    G.M. Reaven, Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988)PubMedCrossRefGoogle Scholar
  35. 35.
    N. Rotondi, W.P. den Elzen, D.C. Bauer, A.R. Cappola, S. Razvi, J.P. Walsh, B.O. Asvold, G. Iervasi, M. Imaizumi, T.H. Collet, A. Bremner, P. Maisonneuve, J.A. Sgarbi, K.T. Khaw, M.P. Vanderpump, A.B. Newman, J. Cornuz, J.A. Franklyn, R.G. Westendorp, E. Vittinghoff, J. Gussekloo, Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 304, 1365–1374 (2010)CrossRefGoogle Scholar
  36. 36.
    G. Michalopoulou, M. Alevizaki, G. Piperingos, D. Mitsibounas, E. Mantzos, P. Adamopoulos, D.A. Koutras, High serum cholesterol levels in persons with “high-normal” TSH levels: should one extend the definition of subclinical hypothyroidism? Eur. J. Endocrinol. 138, 141–145 (1998)PubMedCrossRefGoogle Scholar
  37. 37.
    M.D. Danese, P.W. Ladenson, C.L. Meinert, N.R. Powe, Effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J. Clin. Endocrinol. Metab. 85, 2993–3001 (2000)PubMedCrossRefGoogle Scholar
  38. 38.
    C. Meier, J.J. Staub, C.B. Roth, M. Guglielmetti, M. Kunz, A.R. Miserez, J. Drewe, P. Huber, R. Herzog, B. Müller, TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). J. Clin. Endocrinol. Metab. 86, 4860–4866 (2001)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tomislav Bulum
    • 1
  • Branko Kolarić
    • 2
    • 3
  • Lea Duvnjak
    • 1
    • 4
  1. 1.Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic DiseasesUniversity Hospital MerkurZagrebCroatia
  2. 2.Medical School, University of RijekaRijekaCroatia
  3. 3.Zagreb County Institute of Public HealthZagrebCroatia
  4. 4.Medical School, University of ZagrebZagrebCroatia

Personalised recommendations