@article{3105451, title = "Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation", author = "Chiesa, S.T. and Charakida, M. and McLoughlin, E. and Nguyen, H.C. and Georgiopoulos, G. and Motran, L. and Elia, Y. and Loredana Marcovecchio, M. and Dunger, D.B. and Neil Dalton, R. and Daneman, D. and Sochett, E. and Mahmud, F.H. and Deanfield, J.E.", journal = "EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY", year = "2019", volume = "40", number = "43", pages = "3559-3566", publisher = "Oxford University Press", doi = "10.1093/eurheartj/ehz114", keywords = "hemoglobin A1c; high density lipoprotein; high density lipoprotein cholesterol; nitric oxide; biological marker; high density lipoprotein, adolescent; Article; blood sampling; cardiovascular risk; child; controlled study; disease association; endothelial dysfunction; female; glycemic control; hemoglobin blood level; human; inflammation; insulin dependent diabetes mellitus; kidney failure; lipid fingerprinting; major clinical study; male; microalbuminuria; priority journal; risk factor; scoring system; urine sampling; blood; case control study; chronic disease; complication; hyperlipidemia; inflammation; insulin dependent diabetes mellitus; kidney failure; pathophysiology; vascular endothelium, Adolescent; Biomarkers; Case-Control Studies; Child; Chronic Disease; Diabetes Mellitus, Type 1; Endothelium, Vascular; Female; Humans; Hyperlipidemias; Inflammation; Lipoproteins, HDL; Male; Renal Insufficiency", abstract = "Aims High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed. Methods and results Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05). Conclusion Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology." }