Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

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.

Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus

“…110 With the use of arterial tonometry, augmentation index, a measure that incorporates central arterial stiffness and wave reflections, and pulse-wave velocity, a measure of wave propagation, were found to be increased in children with T1DM. 93,94 Similar results were found in the larger SEARCH cardiovascular study (n=535), which found reduced brachial distensibility in youth with T1DM in addition to increased augmentation index and pulse-wave velocity. 111 Studies that found no increase in arterial stiffness in T1DM used nonstandard methods of assessing arterial stiffness that have not been validated in youth.…”

“…[93][94][95][96][97] Factors associated with this higher cIMT include lower vitamin C levels 98 and longer duration of disease. 99,100 Adolescents with T2DM also demonstrate higher cIMT compared with healthy control subjects, 101,102 with diabetes mellitus duration 103 and glucose control playing a role.…”

Relationship between circulating endothelial progenitor cells and endothelial dysfunction in children with type 1 diabetes: a novel paradigm of early atherosclerosis in high-risk young patients

“…Similar to the others (23), we did not find any relationship between IMT and EPCs; in addition, the relationship between FMD and IMT was not itself strong. However, in the recent study on young patients with long-standing T1DM (over 10 years), numbers of EPCs were an independent determinant of carotid IMT (35). Also, a study in middle-aged patients did find a significant correlation between EPCs and IMT (36).…”

Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function

“…22 Moreover, decreased secretion of NO and vascular endothelial growth factor (VEGF), reduced activity of superoxide dismutase, and impaired function, such as migration and tube formation, are observed in activated late EPCs after exposure to a hyperglycemic condition 23 or advanced glycation end products. 24 Reduced number and function of EPCs are also more prevalent in patients with type 1 and type 2 DM with diabetic nephropathy [25][26][27][28] and macrovascular 26,[29][30][31][32][33] complications and correlate with the degree of atherosclerosis. 34 These observations suggest that the burden of DM-related cardiovascular complications correlates with the number and function of EPCs: alterations in EPCs may contribute to the development and progression of atherosclerosis in patients with DM.…”