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Differential impact of subclinical carotid artery disease on cerebral structure and functioning in type 1 diabetes patients with versus those without proliferative retinopathy

Eelco van Duinkerken12*, Richard G IJzerman1, Nynke J van der Zijl1, Frederik Barkhof3, Petra JW Pouwels4, Menno M Schoonheim35, Annette C Moll6, Jeannette Boerop1, Alette M Wessels27, Martin Klein2, Frank J Snoek2 and Michaela Diamant1

Author Affiliations

1 Diabetes Center/Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117 – Room MF-G417, 1081 HV, Amsterdam, The Netherlands

2 Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands

3 Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

4 Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands

5 Department of Anatomy and Neuroscience, VU University Medical Center, Amsterdam, The Netherlands

6 Department of Ophthalmology, VU University Medical Center, Amsterdam, The Netherlands

7 Eli Lilly and Company, Indianapolis, IN, USA

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Cardiovascular Diabetology 2014, 13:58  doi:10.1186/1475-2840-13-58

Published: 12 March 2014



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.


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.


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.


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.

Type 1 diabetes; Cognition; Subclinical macroangiopathy; Microangiopathy; Neuroimaging; Cognition