Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case-control study.
Adolescent
Age Factors
Animals
Biomarkers
/ blood
Blood Glucose
/ drug effects
Case-Control Studies
Cell Line
Child
Cholesterol, HDL
/ blood
Chromatography, Liquid
Diabetes Mellitus, Type 1
/ blood
Female
Humans
Hypoglycemic Agents
/ therapeutic use
Lipoproteins, HDL
/ blood
Macrophages
/ metabolism
Male
Mice
Proteomics
/ methods
Tandem Mass Spectrometry
Treatment Outcome
Young Adult
A1BG
Cardiovascular
HDL
ITIH4
Proteomics
Type 1 diabetes
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
28 03 2019
28 03 2019
Historique:
received:
16
01
2019
accepted:
18
03
2019
entrez:
30
3
2019
pubmed:
30
3
2019
medline:
14
6
2019
Statut:
epublish
Résumé
Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. This was a cross-sectional case-control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P < 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P < 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091.
Sections du résumé
BACKGROUND
Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition.
METHODS
This was a cross-sectional case-control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification.
RESULTS
Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P < 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P < 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin.
CONCLUSIONS
Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091.
Identifiants
pubmed: 30922315
doi: 10.1186/s12933-019-0846-9
pii: 10.1186/s12933-019-0846-9
pmc: PMC6437869
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Cholesterol, HDL
0
Hypoglycemic Agents
0
Lipoproteins, HDL
0
Banques de données
ClinicalTrials.gov
['NCT02275091']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
43Subventions
Organisme : NCI NIH HHS
ID : P30 CA051008
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA135069
Pays : United States
Organisme : NIH HHS
ID : S10 OD023557
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001409
Pays : United States
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