Adolescents and young adults with youth-onset type 2 diabetes (T2D) are disproportionally
impacted by hyperuricemia compared to non-diabetic peers and youth with type 1 diabetes
(T1D). In fact, 50% of males with youth-onset T2D have serum uric acid (SUA) greater than 6.8
mg/dl. The investigators also recently demonstrated that higher SUA conferred greater odds of
developing hypertension and diabetic kidney disease (DKD) in youth with T2D over 7 years
follow-up. Elevated SUA is thought to lead to cardiovascular disease (CVD) and DKD by
inflammation, mitochondrial dysfunction and deleterious effects on nephron mass. While there
are studies demonstrating beneficial effects of uric acid (UA) lowering on vascular health in
the general population, there are no studies in youth-onset T2D. Youth-onset T2D carries a
greater risk of DKD and CVD compared to adult-onset T2D and T1D.
Accordingly, a clinical trial evaluating UA lowering therapies is needed in youth-onset T2D.
Krystexxa (pegloticase), a uricase, effectively lowers SUA and therefore holds promise as a
novel therapy to impede the development of CVD and DKD in youth-onset T2D. This proposal
describes a pilot and feasibility trial evaluating the effect of UA lowering by pegloticase
on markers of CVD and DKD in ten (n=10) youth aged 18-25 with youth-onset T2D (diagnosed <21
years of age) over 7 days. The overarching hypothesis is that pegloticase improves marker of
cardiorenal health by lowering UA.
Phase:
Phase 2
Details
Lead Sponsor:
University of Colorado Denver School of Medicine Barbara Davis Center