Background:
Type 1 diabetes (T1D) increases CVD risk, and early detection of CV changes could mitigate CVD risk. Increased arterial stiffness is an early marker of adverse CV health and precedes hypertension. Uric acid has been associated with arterial stiffness, hypertension, and CVD in select conditions such as obesity, but its relationship to T1D is undefined. We hypothesized that uric acid predicts increased arterial stiffness and BP over time in youth with T1D, especially those with overweight/obesity.
Methods:
Prospective cohort of 451 participants with T1D from the SEARCH for Diabetes in Youth Study. We measured uric acid, BP, and arterial stiffness assessed by pulse wave velocity (PWV) in the arm (PWV-R), trunk (PWV-T), and lower extremity (PWV-LE). BP and PWV were repeated a mean of 4.5 years later (±1.1). We defined high BP as ≥90
th
%ile for age/sex/height (<13 years) and ≥120/80 mmHg (≥13 years). We applied multivariable regression models to estimate the association of uric acid with annualized changes in each outcome. Directed acyclic graph-informed models were adjusted for age, sex, race/ethnicity, health insurance, family history of CVD, A1c, antihypertensive use, T1D duration, dyslipidemia, and study site. We assessed for effect modification by overweight/obesity.
Results:
Mean age was 18.1 years (±4.5), 50.8% (229/451) were female, 66.1% (298/451) were White, and 42.4% (191/451) had overweight/obesity. A 1 mg/dl increase in uric acid was associated with increased PWV-R (adjusted
β
: 0.02 m/s/year, 95% CI -0.01 to 0.06), decreased SBP (-0.45 mmHg/year, -0.73 to -0.18), and sustained high BP (referenced to normal BP, adjusted OR 1.28, 0.91 to 1.79), but not PWV-T or PWV-LE. Compared to normal BMI, those with overweight/obesity demonstrated somewhat stronger associations between uric acid and PWV-R (0.05 m/s/year, 0.0 to 0.1 vs. 0.0 m/s/year, -0.05 to 0.05, interaction
p
=0.17) and sustained high BP (1.58, 0.99 to 2.51 vs. 0.79, 0.44 to 1.4, interaction
p
=0.06).
Discussion:
Among participants with T1D, uric acid was modestly associated with changes in PWV-R and BP over time, particularly in those with overweight/obesity. Further investigations are warranted to determine uric acid’s role in hypertension and arterial stiffness in T1D.
Burden of Cardiovascular Risk Factors Over Time and Arterial Stiffness in Youth With Type 1 Diabetes Mellitus: The SEARCH for Diabetes in Youth Study