# HDL composition/function and cardiovascular risk in youths with diabetes

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $684,499

## Abstract

According to the World Health Organization, there are over 200 million people with diabetes with up to 1 million
deaths attributed to diabetes annually, and these numbers are expected to double by 2030. Importantly, there
has been a major increase in the incidence of diabetes in children and young adults with the increase in newly
diagnosed T2 diabetes reaching over 40% of the new diabetes cases before the age of 20. Cardiovascular
disease (CVD) begins to develop already in youth, and is marked by arterial stiffness. In youth with diabetes
the arterial stiffness is markedly accelerated. The underlying mechanisms leading to this marked acceleration
of arterial stiffening are not well understood and the current treatments have only limited efficacy. One of the
key mechanisms leading to the arterial stiffness is endothelial dysfunction mediated by decrease in NO
availability and increased inflammation. Recently, high-density lipoprotein (HDL) function, sterol efflux capacity
was shown to be a strong predictor of incident and prevalent CVD independent of HDL-cholesterol (HDL-C)
shifting the paradigm from HDL-C to HDL function as the metric for the HDL anti-atherogenic capacity. We
have strong preliminary data showing that in adults HDL becomes dysfunctional a) in people with T2D, b) in
people with endothelial dysfunction and c) in people with T1D and cardiovascular complications. Moreover, we
have preliminary data showing that specific proteins in HDL can prospectively predict people at risk for
cardiovascular events. We therefore hypothesize that changes in HDL composition and impaired HDL function
in youth with diabetes may be novel risk factors contributing to accelerated arterial stiffness and increased
cardiovascular risk found in this population. We propose to use our state-of-the-art assays to investigate
whether HDL composition and function associates with increased arterial stiffness in youth with diabetes: first,
we will establish the changes in HDL composition and function in youth with T1D or T2D compared to healthy
controls. We will then investigate the role of HDL in arterial stiffening in two complementary studies nested in
SEARCH study. First study will address whether our novel metrics of HDL function associate with increased
arterial stiffness in youth with T2D. Second study will address the same question in youth with T1D. In parallel
in the longitudinal Barbara Davis Center study of youth with T1D we will test whether changes in HDL metrics
associate with changes in arterial stiffness and whether the baseline HDL metrics can predict progression of
arterial stiffness. Collectively, our studies have great potential to discover novel roles for HDL function in early
stages of atherosclerosis progression, and, will advance our understanding of the physiology of the arterial
stiffness and increased cardiovascular risk in youth with diabetes. Identification of novel molecular risk factors
and biological pathways related to arterial stiff...

## Key facts

- **NIH application ID:** 9838255
- **Project number:** 5R01HL144558-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Tomas Vaisar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $684,499
- **Award type:** 5
- **Project period:** 2018-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838255

## Citation

> US National Institutes of Health, RePORTER application 9838255, HDL composition/function and cardiovascular risk in youths with diabetes (5R01HL144558-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9838255. Licensed CC0.

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