Introduction 1 3 1 3 4 5 6 7 8 9 11 12 14 15 7 8 In the present study, we set out to evaluate the potential relationship between structural changes of the carotid artery and hyaluronan metabolism in patients with uncomplicated type 1 diabetes. Subjects and methods We enrolled non-smoking Europid patients with type 1 diabetes, all without clinical signs of micro- or macrovascular disease. The patients were recruited from the Internal Medicine outpatient clinics of the Academic Medical Center and Onze Lieve Vrouwe Gasthuis in Amsterdam, the Netherlands. The presence of macrovascular disease, defined as ECG abnormalities or a history of cardiac, cerebral or peripheral vascular events, was an exclusion criterion for the study. Moreover, subjects with retinopathy, neuropathy, (micro) albuminuria, or hypertension were excluded from participation. All patients were on multiple daily injections of insulin with no other concomitant medication use. Matched non-smoking controls (selected for this study specifically) were unrelated volunteers of similar age and sex. Investigations of both study groups were randomly performed during the study period. Approval for the study was obtained from the Internal Review Board of the Academic Medical Center Amsterdam and all subjects gave written informed consent. The study was carried out in accordance with the principles of the Declaration of Helsinki. 1c 16 Clinical chemistry 1c 8 17 Ultrasound B-mode protocol for cIMT measurement 18 19 Statistical analysis t t p Results 1 1c r p 1 Table 1 Demographic and baseline parameters of the study cohort   Type 1 diabetes patients Controls Number of participants 99 99 Sex (male/female) 44/55 44/55 Age (years) 32.8 ± 14.8 34.9 ± 16.4 Duration of diabetes (years) 16.4 ± 11.9 – Daily insulin dose (IU)  52.9 ± 20.3 – Smoking (yes/no) 0/99 0/99 2 23.4 ± 3.5 23.3 ± 3.6 Systolic blood pressure (mmHg) 123 ± 17 125 ± 20 Diastolic blood pressure (mmHg) 72 ± 9 73 ± 12 Heart rate (beats/min) 71 ± 11** 60 ± 14  Total cholesterol (mmol/l) 4.9 ± 0.9 4.9 ± 1.0 LDL-cholesterol (mmol/l) 2.8 ± 0.7 2.9 ± 0.8 HDL-cholesterol (mmol/l) 1.6 ± 0.5 1.5 ± 0.4 Triacylglycerol (mmol/l) 0.9 (0.5–1.1) 1.0 (0.5–1.2) ASAT (U/l) 24 (21–27) 25 (21–29) ALAT (U/l) 22 (15–28) 20 (14–24) 1c 8.3 ± 1.6** 5.1 ± 0.3 Hyaluronan (ng/ml) 78 ± 43* 60 ± 18 Hyaluronidase (U/ml) 362 ± 23** 242 ± 13 hsCRP (mg/l) 2.6 (0.4–2.9)* 1.1 (0.2–2.0) cIMT (mm) 0.61 ± 0.15** 0.53 ± 0.12 Data are means±SD, except for triacylglycerol, ASAT, ALAT and hsCRP, which are expressed as median (inter-quartile range). p p Fig. 1 a b  p 1 1c 2 Table 2 Univariate and multivariate associations of cIMT with various risk factors in patients with type 1 diabetes Parameter Univariate β coefficient p Multivariate β coefficient p Female sex  −0.86* 0.005 −0.048* 0.029 Age 0.007* 0.001 0.07* 0.0001 Duration of diabetes  0.008* 0.001 −0.110 0.340 Daily insulin dose −0.001 0.109   BMI 0.004 0.433   Mean blood pressure 0.004* 0.004 −0.027 0.726 Heart rate 0.0001 0.994   Total cholesterol 0.016 0.366   LDL-cholesterol 0.021 0.321   HDL-cholesterol 0.026 0.416   Triacylglycerol −0.054 0.076   ASAT 0.037 0.615   ALAT −0.019 0.589   1c −0.008 0.441   Hyaluronan 0.126* 0.001 0.116 0.130 Hyaluronidase 0.036 0.731   hsCRP −0.013 0.306   p Discussion In line with expectation, type 1 diabetes patients were characterised by structural changes of the arterial wall. In addition, we observed significant elevations of plasma hyaluronan and hyaluronidase activity levels in type 1 diabetes patients, whereas hyaluronan was correlated to cIMT. These present data imply that disturbances of hyaluronan metabolism may be associated with vascular damage in type 1 diabetes patients. Intima-media thickness in type 1 diabetes 3 3 1 20 21 1c 1c 1 3 1c 1c Hyaluronan metabolism and type 1 diabetes 7 10 14 15 22 20 23 24 8 19 25 26 27 28 Study limitations 1c 29 30 6 31