The University of Washington has received a USD 1.2 million NHLBI R35 award to investigate the lipoprotein mechanisms driving cardiovascular disease risk in youth with diabetes, reflecting sustained National Institutes of Health interest in closing the translational gap between metabolic biology and early vascular prevention.
The grant, issued under funding opportunity RFA-HL-26-002 and running through February 2033, supports a program led by Karin Bornfeldt, a University of Washington researcher with an h-index of 63 and more than 14,400 citations across 448 published works. The first-year award totals USD 1,233,682 in combined direct and indirect costs.
The program centers on apolipoprotein C3 (APOC3) and its role in governing the size distribution and concentration of triglyceride-rich lipoprotein (TRL) particles and their remnants. Standard LDL-cholesterol lowering, while recommended for children over 10 years of age with elevated cardiovascular risk, leaves a residual CVD burden in people with diabetes that current clinical metrics do not fully account for. The research proposes that adipose tissue insulin resistance — present in both type 1 and type 2 diabetes — drives excess hepatic APOC3 production, which in turn promotes accumulation of a mid-sized atherogenic TRL subpopulation capable of inducing vascular inflammation.
Translational design and youth focus
The program integrates longitudinal studies in youth with type 1 or type 2 diabetes with mechanistic investigation in mouse models of diabetes-accelerated atherosclerosis and cell systems. The longitudinal arm will test whether elevated plasma APOC3 associates with worsening trajectories of insulin resistance and arterial stiffness — an early subclinical marker of atherosclerotic cardiovascular disease — in pediatric and adolescent populations. A separate mechanistic line of inquiry examines whether dysfunction in the hepatic sortilin 1–APOB100 secretion pathway explains the elevated APOC3 output and downstream atherosclerosis observed in diabetes.
The youth emphasis is clinically relevant. Type 2 diabetes incidence in youth is projected by some models to rise by 700% between 2017 and 2060, and youth-onset type 2 diabetes is characterized by more severe insulin resistance than adult-onset disease, with a substantial rate of early arterial stiffening. CVD events also occur at younger ages in people with diabetes than in the general population, making early biomarker identification and preventive intervention a clinical priority that current frameworks do not adequately address.