title: Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia.
abstract: BACKGROUND
  Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR).
  
  
  METHODS
  A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensive and nonsmokers. We measured lipid profile, glucose and insulin levels in plasma, and markers of oxidative stress and inflammation such as oxidized glutathione (GSSG), reduced glutathione (GSH) and TRX.
  
  
  RESULTS
  Familial combined hyperlipidaemia subjects showed significantly higher levels of GSSG, GSSG/GSH ratio and TRX than controls. In addition, FCH individuals with IR showed the worst profile of oxidative stress status compared to controls and FCH patients without IR (P < 0·01). TRX levels correlated with higher insulin resistance.
  
  
  CONCLUSIONS
  Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.|CIBERDEM, Biomedical Network Research Centre in Diabetes and Metabolic Related Diseases, Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martinez-Hervas
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Artero
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.
authors.forename: Juncal
authors.initials: J
authors.lastname: Martinez-Ibañez
authors.affiliation: CIBEROBN, Madrid, Spain.
authors.forename: Mari C
authors.initials: MC
authors.lastname: Tormos
authors.affiliation: CIBERDEM, Biomedical Network Research Centre in Diabetes and Metabolic Related Diseases, Madrid, Spain.|Institute of Health Research-INCLIVA, Valencia, Spain.
authors.forename: Herminia
authors.initials: H
authors.lastname: Gonzalez-Navarro
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Priego
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Martinez-Valls
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia-INCLIVA, Valencia, Spain.|Service of Clinical Analysis, Dr. Peset University Hospital, Valencia, Spain.
authors.forename: Guillermo T
authors.initials: GT
authors.lastname: Saez
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.|CIBERDEM, Biomedical Network Research Centre in Diabetes and Metabolic Related Diseases, Madrid, Spain.
authors.forename: Jose T
authors.initials: JT
authors.lastname: Real
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.|CIBERDEM, Biomedical Network Research Centre in Diabetes and Metabolic Related Diseases, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
authors.affiliation: Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.|CIBERDEM, Biomedical Network Research Centre in Diabetes and Metabolic Related Diseases, Madrid, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013879:Thioredoxins / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D013879:Thioredoxins; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: Atherosclerosis; familial combined hyperlipidaemia; insulin resistance; oxidative stress; thioredoxin