Serum urate and cardiovascular events in the DCCT/EDIC study

Abstract

In type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997-2000, and (a) concurrent MetS and (b) incident 'any CVD' and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p < 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p < 0.0001). During follow-up, 110 participants (11%) experienced "any CVD", and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07-2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01-2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

Figure 1

Distribution of serum urate concentrations in (A) 540 men and (B) 433 women with type 1 diabetes from the DCCT/EDIC cohort in 1997–2000. The vertical lines indicate the upper limit of normal range, 6.8 mg/dl.

Figure 2

Hazard ratios for risk of ‘any CVD’ and MACE in men and women with type 1 diabetes, according to serum urate quartiles (relative to the lowest quartile). Hazard ratios for ‘any CVD’ are shown in (A) for men and (B) for women; those for MACE are shown in (C) for men and (D) for women.