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Background: To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function., Methods: A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER)., Results: Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI., Conclusions: Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: We assessed the association between early increases in albumin excretion and cardiovascular (CV) and renal markers in a large cohort of young people with type 1 diabetes., Research Design and Methods: As part of preliminary screening for a multicenter, randomized controlled trial of statins/ACE inhibitors, we measured albumin-creatinine ratio (ACR) in six early morning urine samples from 3,353 adolescents (10-16 years of age) and calculated tertiles based on an established algorithm. From those subjects deemed to be at higher risk (upper ACR tertile), we recruited 400 into the intervention study (trial cohort). From those subjects deemed to be at lower risk (middle-lower ACR tertiles), we recruited 329 to the observation cohort. At baseline, vascular measurements (carotid intima-media thickness, pulse wave velocity [PWV], flow-mediated dilatation, digital pulse amplitude tonometry), renal markers (symmetric dimethylarginine, cystatin C, creatinine), and CV disease markers (lipids and apolipoproteins [Apo] A-1 and B, C-reactive protein, asymmetric dimethylarginine) were assessed., Results: Age- and sex-adjusted PWV was higher in the trial than in the observational cohort (5.00 ± 0.84 vs. 4.86 ± 0.70 m/s; P = 0.021). Similarly, non-HDL cholesterol (2.95 ± 0.83 vs. 2.81 ± 0.78 mmol/L; P = 0.02) and ApoB-ApoA-1 ratio (0.50 ± 0.14 vs. 0.47 ± 0.11; P = 0.04) were higher in the trial cohort. Cystatin C and creatinine were decreased (0.88 ± 0.13 vs. 0.90 ± 0.13 mg/L, P = 0.04; 51.81 ± 10.45 vs. 55.35 ± 11.05 μmol/L, P < 0.001; respectively) and estimated glomerular filtration rate (137.05 ± 23.89 vs. 129.31 ± 22.41 mL/min/1.73 m(2); P < 0.001) increased in the trial compared with the observational cohort., Conclusions: Our data demonstrate that in adolescents with type 1 diabetes, the group with the highest tertile of albumin excretion showed more evidence of early renal and CV disease than those in the lower tertiles.

The incidence of type 1 diabetes (T1D) is increasing worldwide and is associated with a significant burden, mainly related to the development of vascular complications. Over the last decades, concomitant with the epidemic of childhood obesity, there has been an increasing number of cases of type 2 diabetes (T2D) among children and adolescents. Microvascular complications of diabetes, which include nephropathy, retinopathy and neuropathy, are characterized by damage to the microvasculature of the kidney, retina and neurons. Although clinically evident microvascular complications are rarely seen among children and adolescents with diabetes, there is clear evidence that their pathogenesis and early signs develop during childhood and accelerate during puberty. Diabetic vascular complications are often asymptomatic during their early stages, and once symptoms develop, there is little to be done to cure them. Therefore, screening needs to be started early during adolescence and, in the case of T2D, already at diagnosis. Identification of risk factors and subclinical signs of complications is essential for the early implementation of preventive and therapeutic strategies, which could change the course of vascular complications and improve the prognosis of children, adolescents and young adults with diabetes.

Diabetes mellitus is characterized by chronic hyperglycaemia and a significant risk of developing micro- and macrovascular complications. Growing evidence suggests that increased oxidative stress, induced by several hyperglycaemia-activated pathways, is a key factor in the pathogenesis of endothelial dysfunction and vascular disease. Reactive oxidant molecules, which are produced at a high rate in the diabetic milieu, can cause oxidative damage of many cellular components and activate several pathways linked with inflammation and apoptosis. Among the mechanisms involved in oxidative stress generation, mitochondria and uncoupling proteins are of particular interest and there is growing evidence suggesting their pivotal role in the pathogenesis of diabetic complications. Other important cellular sources of oxidants include nicotinamide adenine dinucleotide phosphate oxidases and uncoupling endothelial nitric oxide synthase. In addition, diabetes is associated with reduced antioxidant defences, which generally contrast the deleterious effect of oxidant species. This concept underlines a potential beneficial role of antioxidant therapy for the prevention and treatment of diabetic vascular disease. However, large scale trials with classical antioxidants have failed to show a significant effect on major cardiovascular events, thus underlying the need of further investigations in order to develop therapies to prevent and/or delay the development of micro- and macrovascular complications.