title: Glucosepane and oxidative markers in skin collagen correlate with intima media thickness and arterial stiffness in long-term type 1 diabetes.
abstract: OBJECTIVE
  To study intima media thickness (cIMT) and arterial stiffness in type 1 diabetes of long duration, and their associations with the collagen cross-linker glucosepane and inflammatory and oxidative markers.
  
  
  METHODS
  Twenty-seven individuals with type 1 diabetes mellitus of 40 years duration from the Oslo Study cohort and 24 age-matched controls were included. cIMT measurements of the carotid artery were performed longitudinally. Pulse wave velocity (PWV), augmentation index (AIx) and augmentation pressure (AP) were assessed cross-sectionally. Glucosepane and the oxidative product methionine sulfoxide (MetSO) were determined in skin collagen by liquid chromatography-mass spectrometry. Circulating inflammatory markers were determined by ELISAs.
  
  
  RESULTS
  The diabetes patients had significantly increased cIMT and arterial stiffness compared to controls. Significant correlations were noted for skin glucosepane with cIMT (r=0.41) and PWV (r=0.44). Skin MetSO and monocyte chemoattractant protein-1 (MCP-1) correlated significantly with AIx and AP. After correcting for age and mean arterial pressure in multiple linear regression analysis, MetSO and MCP-1 were both independently associated with AIx and AP.
  
  
  CONCLUSIONS
  These results suggest more premature atherosclerosis and arterial pathology in individuals with diabetes compared to age-matched controls. They also suggest an association between the arterial pathology and markers of collagen crosslinking, oxidative damage and inflammation in type 1 diabetes patients of forty years disease duration.
authors.affiliation: Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine University of Oslo, Oslo, Norway. Electronic address: k.a.sveen@medisin.uio.no.
authors.forename: Kari Anne
authors.initials: KA
authors.lastname: Sveen
authors.affiliation: Department of Pediatrics, Oslo University Hospital, Ullevaal, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine University of Oslo, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Dahl-Jørgensen
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Knut Haakon
authors.initials: KH
authors.lastname: Stensaeth
authors.affiliation: Department of Cardiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Angel
authors.affiliation: Department of Cardiology, Oslo University Hospital, Oslo, Norway; Center for Clinical Heart Research, Oslo University hospital, Ullevaal, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine University of Oslo, Oslo, Norway.
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
authors.affiliation: Departments of Pathology and Biochemistry Case Western Reserve University, Cleveland, OH, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Sell
authors.affiliation: Departments of Pathology and Biochemistry Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Monnier
authors.affiliation: Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine University of Oslo, Oslo, Norway.
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Hanssen
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D059289:Vascular Stiffness; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; C543060:glucosepane; D003094:Collagen
keywords: Arterial stiffness; Diabetes mellitus; Glucosepane; Methionine sulfoxide; Type 1