title: Low-normal free thyroxine confers decreased serum bilirubin in type 2 diabetes mellitus.
abstract: BACKGROUND
  Bilirubin may confer cardiovascular protection because of its strong antioxidative properties. Both thyroid dysfunction and the diabetic state affect bilirubin metabolism. Here we tested whether low-normal thyroid function affects serum bilirubin among euthyroid subjects with and without type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Serum total bilirubin, thyrotropin and free thyroxine (free T4), transaminases, insulin sensitivity (homeostasis model assessment), and lipids were measured in 74 T2DM and 82 nondiabetic subjects with thyrotropin and free T4 levels within the euthyroid range.
  
  
  RESULTS
  Bilirubin was positively related to free T4 in T2DM subjects (r = 0.370, p < 0.001), but not in nondiabetic subjects (r = 0.047, p = 0.68). In age- and sex-adjusted multiple linear regression analysis, free T4 was found to interact positively with the presence of T2DM on serum bilirubin (interaction term: β = 0.251, p = 0.024). This interaction remained present after additional adjustment for alcohol intake, aspartate aminotransferase and insulin sensitivity (interaction term: β = 0.222, p = 0.043), or alternatively for cholesterol and triglycerides (interaction term: β = 0.203, p = 0.057).
  
  
  CONCLUSIONS
  Lower free T4 levels within the euthyroid range confer decreased bilirubin in T2DM. Low-normal thyroid function could enhance atherosclerosis susceptibility in T2DM by decreasing serum bilirubin.
authors: Department of Internal Medicine, University of Groningen and University Medical Center Groningen , Groningen, The Netherlands .
authors: Petronella E
authors: PE
authors: Deetman
authors: Arjan J
authors: AJ
authors: Kwakernaak
authors: Stephan J L
authors: SJ
authors: Bakker
authors: Robin P F
authors: RP
authors: Dullaart
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D001663:Bilirubin / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012044:Regression Analysis; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000378:metabolism / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*; D014280:Triglycerides / Q000097:blood
chemical_list: D000975:Antioxidants; D007328:Insulin; D014280:Triglycerides; D013972:Thyrotropin; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D013974:Thyroxine; D001663:Bilirubin
references: Curr Pharm Des. 2008;14(5):412-21
references: 18289068
references: Hepatology. 1989 Feb;9(2):314-21
references: 2536351
references: Diabetologia. 2005 Mar;48(3):529-38
references: 15729582
references: JAMA. 2006 Mar 1;295(9):1033-41
references: 16507804
references: Diabetes Care. 2010 Oct;33(10):e131
references: 20876705
references: Endocrine. 2011 Feb;39(1):28-32
references: 21072691
references: Transpl Int. 2012 Aug;25(8):876-81
references: 22716194
references: Front Pharmacol. 2012 Apr 03;3:55
references: 22493581
references: PLoS One. 2010 Aug 25;5(8):e12371
references: 20811623
references: Ann Intern Med. 2008 Jun 3;148(11):832-45
references: 18490668
references: Am J Gastroenterol. 2003 May;98(5):960-7
references: 12809815
references: Clin Chim Acta. 2012 Dec 24;414:161-5
references: 23010146
references: Science. 1987 Feb 27;235(4792):1043-6
references: 3029864
references: Cardiovasc Res. 1997 Apr;34(1):55-68
references: 9217873
references: Clin Endocrinol (Oxf). 2012 Apr;76(4):526-32
references: 21848645
references: Am J Physiol. 1972 May;222(5):1091-9
references: 5022368
references: Curr Opin Lipidol. 2006 Oct;17(5):510-8
references: 16960499
references: JAMA. 2010 Sep 22;304(12):1365-74
references: 20858880
references: Clin Endocrinol (Oxf). 2012 Dec;77(6):911-7
references: 22724581
references: Clin Endocrinol (Oxf). 2009 Mar;70(3):469-74
references: 18727709
references: Atherosclerosis. 2011 Dec;219(2):728-33
references: 21840000
references: Atherosclerosis. 2009 Jun;204(2):e77-81
references: 18977482
references: J Clin Endocrinol Metab. 1984 Sep;59(3):521-5
references: 6430948
references: Biochim Biophys Acta. 1991 Oct 10;1075(2):119-22
references: 1657172
references: Atherosclerosis. 2013 Mar;227(1):18-25
references: 23159101
references: J Endocrinol. 2000 Jun;165(3):599-606
references: 10828843
references: Mol Aspects Med. 1987;9(5):391-404
references: 3306238
references: J Biol Chem. 1994 Jun 17;269(24):16712-9
references: 8206992
references: Vasc Med. 2009 May;14(2):129-36
references: 19366819
references: J Neurosci Methods. 2005 Apr 30;143(2):209-16
references: 15814153
references: Diabetologia. 2013 Apr;56(4):683-5
references: 23354127
references: Clin Endocrinol (Oxf). 2008 Mar;68(3):375-81
references: 17877759
references: Am J Cardiol. 2011 Nov 15;108(10):1438-42
references: 21864819
references: Cerebrovasc Dis. 2006;21(5-6):408-14
references: 16534198
references: Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):458-63
references: 21088253
references: Clin Endocrinol (Oxf). 2007 Nov;67(5):668-73
references: 17596198
references: Exp Biol Med (Maywood). 2003 May;228(5):568-71
references: 12709588
references: Kidney Int. 2011 Mar;79(6):686
references: 21358656
references: Am J Med. 1959 Feb;26(2):214-27
references: 13617278
references: Eur J Clin Invest. 2012 May;42(5):487-95
references: 21955281
references: Mol Cell Endocrinol. 2011 Jun 6;339(1-2):54-62
references: 21458530