title: Low normal free T4 confers decreased high-density lipoprotein antioxidative functionality in the context of hyperglycaemia.
abstract: OBJECTIVE
  Low normal thyroid function may promote the development of atherosclerotic cardiovascular disease by thus far poorly defined mechanisms. We tested the impact of thyroid function on HDL antioxidative capacity, a metric of its antiatherogenic functionality, in euthyroid subjects with varying degrees of glucose tolerance.
  
  
  METHODS
  Seventy subjects with Type 2 diabetes mellitus (T2DM), 37 subjects with impaired fasting glucose (IFG) and 31 subjects with normal fasting glucose (NFG) (revised NCEP-ATPIII criteria) participated in a cross-sectional study.
  
  
  METHODS
  HDL antioxidative capacity (standardized for HDL cholesterol) was measured as the percentage inhibition of low-density lipoprotein oxidation in vitro.
  
  
  RESULTS
  TSH, free T4 and HDL antioxidative capacity were not different among NFG, IFG and T2DM subjects (P > 0·25 for each). HDL antioxidative capacity was correlated positively with free T4 (r = 0·320, P = 0·007), and negatively with plasma glucose (r = -0·394, P < 0·001) in T2DM only. Taking account of age and sex, the relationship of HDL antioxidative functionality with free T4 was modified by glucose tolerance status (P = 0·040 and P = 0·008 for interactions of IFG and T2DM with free T4 respectively). Prevailing plasma glucose also interacted positively with free T4 on HDL antioxidative capacity (P = 0·054).
  
  
  CONCLUSIONS
  In the context of chronic hyperglycaemia, low free T4 within the euthyroid range confers diminished HDL antioxidative capacity, a pathophysiologically relevant metric of HDL functionality.
authors.affiliation: Department of Endocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
authors.forename: Michela
authors.initials: M
authors.lastname: Triolo
authors.forename: Jan Freark
authors.initials: JF
authors.lastname: de Boer
authors.forename: Wijtske
authors.initials: W
authors.lastname: Annema
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012044:Regression Analysis; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000097:blood*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D008075:Lipoproteins, HDL; D013963:Thyroid Hormones; D013974:Thyroxine