Thyroid hormones have generally been found normal in diabetic patients. The question of whether variation within the euthyroid range influences insulin sensitivity in type 2 diabetes remains to be established. To investigate this, a meal was given to four groups: 17 healthy volunteers (controls), 22 first-degree relatives of type 2 diabetic subjects (relatives), 15 subjects with impaired glucose tolerance (IGT), and 24 subjects with overt type 2 diabetes (DM). Blood was drawn for 360 min for measurements of glucose and insulin. Plasma-free-T4(FT4) and plasma-free-T3(FT3) levels were measured. Fasting and postprandial insulin resistance was assessed by HOMA-IR and ISI indices, respectively. FT4 levels were found to be lower in controls (13.73 ± 0.48 pmol/l) than relatives, IGT, and DM (15.33 ± 0.52, 16.13 ± 0.65, and 17.7 ± 0.85 pmol/l, respectively, P = 0.007). FT3 levels were lower in controls (3.68 ± 0.09 pmol/l) than in relatives, IGT, and DM (4.35 ± 0.1, 4.8 ± 0.067, and 4.87 ± 0.11 pmol/l, respectively, P = 0.001). HOMA-IR was positively associated with FT4 and FT3 levels (β-co-efficient = 1.876 ± 0.476, P = 0.001; and 0.406 ± 0.090, P = 0.001, respectively). ISI was negatively associated with FT4 and FT3 levels (β-co-efficient = −0.051 ± 0.009, P = 0.001 and −0.009 ± 0.002, P = 0.001, respectively). In conclusion, increases of thyroid hormone levels within the normal range associate positively with insulin resistance. These data suggest that thyroid hormones may be part of the pathogenetic mechanism to explain metabolic derangement early in the development of type 2 diabetes.
Insulin resistance Thyroid hormones Type 2 diabetes
This is a preview of subscription content, log in to check access.
The authors thank E. Pappas for the technical support and V. Frangaki, R.N. for the nursing help.
Conflict of interest
The authors declare that “no financial conflict of interest exists”.
S.R. Kim, E.S. Tull, E.O. Talbott, M.T. Vogt, L.H. Kuller, A hypothesis of synergism: the interrelationship of T3 and insulin to disturbances in metabolic homeostasis. Med. Hypotheses 59, 650–666 (2002)Google Scholar
A. Wennlund, P. Felig, L. Hagenfeldt, J. Warhen, Hepatic glucose production and splanchnic glucose exchange in hyperthyroidism. J. Clin. Endocrinol. Metab. 62, 174–180 (1986)CrossRefPubMedGoogle Scholar
G. Dimitriadis, B. Baker, H. Marsh, L. Mandarino, R. Rizza, R. Bergman et al., Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am. J. Physiol. 248, 593–601 (1985)Google Scholar
G. Dimitriadis, P. Mitrou, V. Lambadiari, E. Boutati, E. Maratou, E. Koukkou et al., Glucose and lipid fluxes in the adipose tissue after meal ingestion in hyperthyroidism. J. Clin. Endocrinol. Metab. 91, 1112–1118 (2006)CrossRefPubMedGoogle Scholar
G. Dimitriadis, P. Mitrou, V. Lambadiari, E. Boutati, E. Maratou, D.B. Panagiotakos et al., Insulin action in adipose tissue and muscle in hypothyroidism. J. Clin. Endocrinol. Metab. 91, 4930–4937 (2006)CrossRefPubMedGoogle Scholar
E. Ortega, J. Koska, N. Pannacciulli, J.C. Bunt, J. Krakoff, Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals. Eur. J. Endocrinol. 158, 217–221 (2008)CrossRefPubMedGoogle Scholar
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)CrossRefPubMedGoogle Scholar
S.A. Chubb, W. 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)CrossRefPubMedGoogle Scholar
D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations. Diabetologia 28, 412–419 (1985)CrossRefPubMedGoogle Scholar
M. Gutt, C.L. Davis, S.B. Spitzer, M.M. Llabre, M. Kumar, E.M. Czarnecki et al., Validation of the insulin sensitivity index (ISI 1, 120): comparison with other measures. Diabetes Res. Clin. Pract. 47, 177–184 (2000)CrossRefPubMedGoogle Scholar
D.G. Yavuz, M. Yüksel, O. Deyneli, Y. Ozen, H. Aydin, S. Akalin, Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goiter patients. Clin. Endocrinol. (Oxf). 61, 515–521 (2004)CrossRefGoogle Scholar
J.I. Botella-Carretero, F. Alvarez-Blasco, J. Sancho, H.F. Escobar-Morreale, Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal. Thyroid 16, 397–402 (2006)CrossRefPubMedGoogle Scholar
C.S. Pittman, A.K. Suda, J.B. Chambers Jr, G.Y. Ray, Impaired 3,5,3′- triiodothyronine (T3) production in diabetic patients. Metabolism 28, 333–338 (1979)CrossRefPubMedGoogle Scholar
C.M. Alexander, E.M. Kaptein, S.M. Lum, C.A. Spencer, D. Kumar, J.T. Nicoloff, Pattern of recovery of thyroid hormone indices associated with treatment of diabetes mellitus. J. Clin. Endocrinol. Metab. 54, 362–366 (1982)CrossRefPubMedGoogle Scholar
R. Naeije, J. Golstein, N. Clumeck, H. Meinhold, K.W. Wenzel, L. Vanhaelst, A low T3 syndrome in diabetic ketoacidosis. Clin. Endocrinol. (Oxf). 8, 467–472 (1978)CrossRefGoogle Scholar
C.S. Pittman, A.K. Suda, J.B. Chambers Jr, H.G. McDaniel, G.Y. Ray, B.K. Preston, Abnormalities of thyroid hormone turnover in patients with diabetes mellitus before and after insulin therapy. J. Clin. Endocrinol. Metab. 48, 854–860 (1979)CrossRefPubMedGoogle Scholar
J.L. Schlienger, A. Anceau, G. Chabrier, M.L. North, F. Stephan, Effect of diabetic control on the level of circulating thyroid hormones. Diabetologia 22, 486–488 (1982)CrossRefPubMedGoogle Scholar
S. Madsbad, P. Laurberg, J. Weeke, H. Orskov, O.K. Faber, C. Binder, Very early changes in circulating T3 and rT3 during the development of metabolic derangement in diabetic patients. Acta Med. Scand. 209, 385–387 (1981)CrossRefPubMedGoogle Scholar
E. Maratou, D.J. Hadjidakis, A. Kollias, K. Tsegka, M. Peppa, M. Alevizaki et al., Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur. J. Endocrinol. 160, 785–790 (2009)CrossRefPubMedGoogle Scholar
D.G. Yavuz, D. Yazici, A. Toprak, O. Deyneli, H. Aydin, M. Yüksel et al., Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients. Thyroid 18, 395–400 (2008)CrossRefPubMedGoogle Scholar
E. Maratou, D.J. Hadjidakis, M. Peppa, M. Alevizaki, K. Tsegka, V. Lambadiari et al. (2010). Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism. Eur. J. Endocrinol. 163, 625–630 (2010)CrossRefPubMedGoogle Scholar