title: Plasma homocysteine and S-adenosylmethionine in erythrocytes as determinants of carotid intima-media thickness: different effects in diabetic and non-diabetic individuals. The Hoorn Study.
abstract: OBJECTIVE
  Hyperhomocysteinemia is a risk factor for atherothrombosis. Through unknown mechanisms, individuals with type 2 diabetes appear particularly susceptible. We determined whether components of homocysteine metabolism are associated with intima-media thickness in individuals with and without type 2 diabetes.
  
  
  RESULTS
  In a cross-sectional design, we studied 231 Caucasian individuals, 60.6% having type 2 diabetes. We measured fasting homocysteine, vitamin B6 and vitamin B12 in plasma, and folate, S-adenosylmethionine and S-adenosylhomocysteine in plasma and erythrocytes. A homocysteine concentration >12 micromol/l was associated with a greater intima-media thickness of +0.07 mm (95% CI, +0.01 to +0.13; P=0.03) among diabetic individuals and of -0.004 mm (95%CI, -0.08 to +0.07; P=0.92) among non-diabetic individuals. An erythrocyte S-adenosylmethionine concentration above >4000 nmol/l was associated with a smaller intima-media thickness of -0.04 mm (95%CI, -0.10 to +0.02; P=0.17) for diabetic individuals versus -0.12 mm (95%CI, -0.20 to -0.36; P=0.005) for non-diabetic individuals.
  
  
  CONCLUSIONS
  With regard to carotid intima-media thickness, individuals with diabetes appear more susceptible to the detrimental effects of homocysteine than non-diabetic individuals. In addition, diabetic individuals may lack the protective effect on the vascular wall conferred by high concentrations of S-adenosylmethionine. These findings may help explain why hyperhomocysteinemia is an especially strong risk factor for atherothrombosis among individuals with type 2 diabetes.
authors.affiliation: Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Becker
authors.forename: R M A
authors.initials: RM
authors.lastname: Henry
authors.forename: P J
authors.initials: PJ
authors.lastname: Kostense
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: T
authors.initials: T
authors.lastname: Teerlink
authors.forename: S
authors.initials: S
authors.lastname: Zweegman
authors.forename: J M
authors.initials: JM
authors.lastname: Dekker
authors.forename: G
authors.initials: G
authors.lastname: Nijpels
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
authors.forename: L M
authors.initials: LM
authors.lastname: Bouter
authors.forename: Y M
authors.initials: YM
authors.lastname: Smulders
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology*; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012436:S-Adenosylmethionine / Q000097:blood*; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology*; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
chemical_list: D006710:Homocysteine; D012436:S-Adenosylmethionine; D025101:Vitamin B 6; D014805:Vitamin B 12