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Diabetes Care. 2020 Jan;43(1):178-186. doi: 10.2337/dc19-0772. Epub 2019 Oct 9.

High Concentration of Medium-Sized HDL Particles and Enrichment in HDL Paraoxonase 1 Associate With Protection From Vascular Complications in People With Long-standing Type 1 Diabetes.

Author information

1
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA.
2
Research Division, Joslin Diabetes Center, Boston, MA.
3
Department of Medicine, Harvard Medical School, Boston, MA.
4
Diabetes Program, Benaroya Research Institute, Seattle, WA.
5
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA bornf@uw.edu.
6
Department of Pathology, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA.

Abstract

OBJECTIVE:

A subset of people with long-standing type 1 diabetes (T1D) appears to be protected from microvascular and macrovascular complications. Previous studies have focused on improved abilities to respond to glucose and its downstream effects as protective mechanisms. It is unclear whether lipoproteins play a role in the vascular health of these people. We therefore determined whether HDL particle concentration, size, function, and/or protein composition associate with protection from vascular complications.

RESEARCH DESIGN AND METHODS:

We studied two independent cross-sectional cohorts with T1D: the T1D Exchange Living Biobank (n = 47) and the Joslin Medalist Study (n = 100). Some of the subjects had vascular complications, whereas others never exhibited vascular complications, despite an average duration of diabetes in the cohorts of 45 years. We assessed HDL particle size and concentration by calibrated ion mobility analysis, the HDL proteome by targeted mass spectrometry, and HDL function ex vivo by quantifying cholesterol efflux capacity and inhibition of monocyte adhesion to endothelial cells.

RESULTS:

In both cohorts, people without vascular complications exhibited significantly higher concentrations of medium-sized HDL particles (M-HDL) independently of total and HDL cholesterol levels. While no consistent differences in HDL functions were observed ex vivo, people without vascular complications had higher levels of HDL-associated paraoxonase 1 (PON1), an enzyme that inhibits atherosclerosis in animal models.

CONCLUSIONS:

Elevated concentrations of M-HDL particles and elevated levels of HDL-associated PON1 may contribute to long-term protection from the vascular complications of diabetes by pathways that are independent of total cholesterol and HDL cholesterol.

PMID:
31597668
PMCID:
PMC6925582
[Available on 2021-01-01]
DOI:
10.2337/dc19-0772

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