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Eur Heart J. 2019 Mar 12. pii: ehz114. doi: 10.1093/eurheartj/ehz114. [Epub ahead of print]

Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation.

Author information

1
Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, UK.
2
1st Cardiology Clinic, University of Athens, Hippokratio Hospital, Athens, Greece.
3
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
4
Department of Paediatrics, University of Cambridge, Cambridge, UK.
5
Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
6
WellChild Laboratory, St. Thomas' Hospital, King's College London, London, UK.

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.

KEYWORDS:

Adolescents ; Endothelial function ; HDL function ; Inflammation; Type 1 diabetes

PMID:
30863865
DOI:
10.1093/eurheartj/ehz114

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