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

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 (1.690.41 vs. 1.440.29mmol/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 O-2 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.