LAUSR

Persons with type 1 diabetes (T1D) have increased risk of cardiovascular disease. Large artery stiffness is an important determinant of cardiovascular risk. Carotid–femoral pulse wave velocity (cfPWV) is considered the gold standard measure of arterial stiffness, and has been shown to be a strong predictor of mortality and cardiovascular outcome [1]. Arterial stiffening reflects fragmentation and loss of elastin fibers and accumulation of collagen fibers in the media of large arteries. However, the mechanisms responsible for arterial stiffening remain incompletely understood [2]. In this cross-sectional study, we measured two biomarkers reflecting collagen formation and degradation, namely PRO-C6, which detects the C-terminal pro-peptide of type VI collagen released upon normal maturation of the collagen and C3M which is a specific fragment of type III collagen generated by matrix metalloproteinase 9 [3, 4]. High serological levels of PRO-C6 and C3M have been observed in patients with cardiovascular disease [4]. However, the association between cfPWV and PRO-C6 and C3M has never been evaluated before. We, therefore, evaluated the associations between cfPWV and PRO-C6 and C3M measured in serum and urine in 634 persons with T1D and various degrees of diabetic nephropathy. The participants were stratified according to different stages of nephropathy as one of the aims of the overall study was to examine the relation between arterial stiffness and diabetes complications [5]. The participants were recruited from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Written informed patient consent and ethical approval of the study were obtained. The details of the study have previously been described [5]. PRO-C6 and C3M in serum and urine were measured with the enzyme-linked immunosorbent assay (ELISA) method developed by Nordic Bioscience, Denmark [3, 4]. cfPWV was measured with the SphygmoCor device (Actor Medical, Sydney, Australia) by trained laboratory technicians following 15 min of supine rest. Three measurements were performed and averaged. We applied unadjusted and adjusted linear regression analyses. Adjustment included sex, age, mean arterial pressure, LDL cholesterol, smoking, HbA1c, treatment with renin–angiotensin–aldosterone system blockers, estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (UACR). To adjust for urine output levels, the urinary markers were normalized for urinary creatinine. We tested for effect modulation in the associations for the influence of different stages of nephropathy by introducing the appropriate interaction term in the regression models. Of the 634 participants, 349 (55%) were male, mean ± SD age was 54.6 ± 12.6 years, eGFR 81 ± 26 ml/ min/1.73 m2, systolic blood pressure 132 ± 17 mmHg and cfPWV 10.4 ± 3.3 m/s. Table 1 shows the unadjusted and adjusted associations between cfPWV and the biomarkers. Higher serum and urinary levels of the collagen formation marker PRO-C6 were associated with higher cfPWV in unadjusted models (p ≤ 0.039). After adjustment only higher serum level remained significantly associated with higher cfPWV (β estimate per doubling of serum PRO-C6: 0.48 ± 0.21; p = 0.026). Higher serum level of the collagen degradation marker C3M was associated with higher cfPWV in the unadjusted model (p = 0.002), but significance was lost after adjustment (p = 0.24). Higher urinary level of C3M was associated with lower cfPWV in the unadjusted model (p < 0.001), but significance was lost after adjustment (p = 0.44). Managed By Antonio Secchi.