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

Marietta Charakida; Scott Chiesa; Evie McLoughlin; Helen Nguyen; George Georgiopoulos; L Motran; Y Elia; ML Marcovecchio; D Dunger; RN Dalton; D Daneman; E Sochett; FH Mahmud; JE Deanfield

doi:10.1093/eurheartj/ehz114

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

Marietta Charakida, Scott Chiesa, Evie McLoughlin, Helen Nguyen, George Georgiopoulos, L Motran, Y Elia, ML Marcovecchio, D Dunger, RN Dalton, D Daneman, E Sochett, FH Mahmud, JE Deanfield

UCL University College London

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3559-3566
Number of pages	8
Journal	European Heart Journal
Volume	40
Issue number	43
Early online date	Mar 2019
DOIs	https://doi.org/10.1093/eurheartj/ehz114
Publication status	Published - Mar 2019

Keywords

Adolescents
Endothelial function
HDL function
Inflammation
Type 1 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/eurheartj/ehz114

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Charakida, M., Chiesa, S., McLoughlin, E., Nguyen, H., Georgiopoulos, G., Motran, L., Elia, Y., Marcovecchio, ML., Dunger, D., Dalton, RN., Daneman, D., Sochett, E., Mahmud, FH., & Deanfield, JE. (2019). Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation. European Heart Journal, 40(43), 3559-3566. https://doi.org/10.1093/eurheartj/ehz114

@article{f7cf10f38426498f8617fa4ca9cde3ef,

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

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",

author = "Marietta Charakida and Scott Chiesa and Evie McLoughlin and Helen Nguyen and George Georgiopoulos and L Motran and Y Elia and ML Marcovecchio and D Dunger and RN Dalton and D Daneman and E Sochett and FH Mahmud and JE Deanfield",

year = "2019",

month = mar,

doi = "10.1093/eurheartj/ehz114",

language = "English",

volume = "40",

pages = "3559--3566",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "43",

}

Charakida, M, Chiesa, S, McLoughlin, E, Nguyen, H, Georgiopoulos, G, Motran, L, Elia, Y, Marcovecchio, ML, Dunger, D, Dalton, RN, Daneman, D, Sochett, E, Mahmud, FH & Deanfield, JE 2019, 'Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation.', European Heart Journal, vol. 40, no. 43, pp. 3559-3566. https://doi.org/10.1093/eurheartj/ehz114

TY - JOUR

T1 - Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation.

AU - Charakida, Marietta

AU - Chiesa, Scott

AU - McLoughlin, Evie

AU - Nguyen, Helen

AU - Georgiopoulos, George

AU - Motran, L

AU - Elia, Y

AU - Marcovecchio, ML

AU - Dunger, D

AU - Dalton, RN

AU - Daneman, D

AU - Sochett, E

AU - Mahmud, FH

AU - Deanfield, JE

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - Adolescents

KW - Endothelial function

KW - HDL function

KW - Inflammation

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85075115606&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehz114

DO - 10.1093/eurheartj/ehz114

M3 - Article

SN - 0195-668X

VL - 40

SP - 3559

EP - 3566

JO - European Heart Journal

JF - European Heart Journal

IS - 43

ER -

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

Abstract

Keywords

UN SDGs

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