Abstract
BackgroundCarotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.MethodsSixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured.ResultsAfter adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP.ConclusionsOur findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.
Highlights
Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM)
This hypothesis was further confirmed in a recent study on young T1DM patients [7] that demonstrated a severe impairment of flow-mediated vasodilation (FMD), important reduction in bone marrow derived circulating endothelial progenitor cells (EPCs), moderate increase in carotid artery intima-media thickness (C-IMT) and an inverse relationship between FMD and C-IMT
The results of this study suggest that young subjects with relatively long-lasting T1DM and free of overt clinical complications, have a significantly lower count of circulating EPCs and a generalized preclinical involvement of large artery structure and function as compared to healthy controls
Summary
Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). Endothelial dysfunction has been suggested to anticipate structural changes in large artery wall in young T1DM patients [5], in keeping with the hypothesis that functional abnormalities of the endothelium represent an early marker of atherosclerosis but above all a pathophysiologic mechanism promoting the development of arterial wall thickening and stiffening [6] This hypothesis was further confirmed in a recent study on young T1DM patients [7] that demonstrated a severe impairment of FMD, important reduction in bone marrow derived circulating endothelial progenitor cells (EPCs), moderate increase in C-IMT and an inverse relationship between FMD and C-IMT. Reports on large artery stiffness in young diabetic patients are still limited and indirect, based mainly on applanation tonometry [12,13]
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