title: Differential impact of subclinical carotid artery disease on cerebral structure and functioning in type 1 diabetes patients with versus those without proliferative retinopathy.
abstract: BACKGROUND
  Type 1 diabetes mellitus (T1DM) is associated with cerebral compromise, typically found in patients with microangiopathy. Associations between subclinical macroangiopathy and the brain, whether or not in the presence of microangiopathy, have not been fully explored in T1DM. We hypothesized that subclinical macroangiopathy in adult T1DM may affect the brain and interacts with microangiopathy.
  
  
  METHODS
  In 51 asymptomatic T1DM patients with, 53 without proliferative retinopathy and 51 controls, right common carotid artery ultrasound was used to assess intima media thickness (cIMT) and distensibility (cD). Neuropsychological tests for cognitive functions, and magnetic resonance imagining for white matter integrity and functional connectivity, i.e. neuronal communication, were used.
  
  
  RESULTS
  After correction for confounders, cIMT was borderline significantly increased in all T1DM patients (P = 0.071), whereas cD was not statistically significantly altered (P = 0.45). Patients with proliferative retinopathy showed the largest increase in cIMT and decrease in cD. In all participants, after adjustment for confounders, increased cIMT was related to decreased white matter integrity (β = -0.198 P = 0.041) and decreased functional connectivity in visual areas (β = -0.195 P = 0.046). For cognition, there was a significant interaction between cIMT and the presence of proliferative retinopathy after adjustment for confounding factors (all P < 0.05). Increased cIMT was associated with lower general cognitive ability (β = -0.334; P = 0.018), information processing speed (β = -0.361; P = 0.010) and attention (β = -0.394; P = 0.005) scores in patients without, but not in patients with proliferative retinopathy.
  
  
  CONCLUSIONS
  These findings suggest that subclinical macroangiopathy may be a factor in the development of diabetes-related cognitive changes in uncomplicated T1DM, whereas in patients with advanced T1DM, proliferative retinopathy may rather be the driving force of cerebral compromise.
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 - Room MF-G417, 1081 HV, Amsterdam, The Netherlands. e.vanduinkerken@vumc.nl.
authors.forename: Eelco
authors.initials: E
authors.lastname: van Duinkerken
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ijzerman
authors.forename: Nynke J
authors.initials: NJ
authors.lastname: van der Zijl
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.forename: Annette C
authors.initials: AC
authors.lastname: Moll
authors.forename: Jeannette
authors.initials: J
authors.lastname: Boerop
authors.forename: Alette M
authors.initials: AM
authors.lastname: Wessels
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Snoek
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000293:Adolescent; D000328:Adult; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D049109:Cell Proliferation; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D055815:Young Adult