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.
Highlights
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
Higher serum urate (SU) was associated with higher BMI, higher mean DCCT/EDIC HbA1c, higher triglycerides, lower Estimated glomerular filtration rates (eGFR), the presence of microalbuminuria, and the presence of MetS
Higher SU was associated with younger age, DCCT secondary intervention cohort, longer duration of diabetes, higher pulse rate, hypertension, higher total and LDL-cholesterol concentrations, lower HDL-cholesterol concentrations, lower eGDR, higher C-Reactive Protein (CRP), and use of angiotensin converting enzyme (ACE) or angiotensin II receptor blocker (ARB) medications
Summary
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. 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. The sex-specific associations between SU and subsequent vascular events in T1D remain poorly defined To address this deficit, we utilized the remarkable long-term data collected by the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. We determined sex-specific associations of SU with concurrent clinical status including features of the M etS4,8–11, related SU to ‘any CVD’ event and ‘major adverse cardiovascular events’ (MACE) occurring over a median of 14 years of follow-up. These subjects represented 71% of the 1375 EDIC participants and were representative of the entire DCCT/EDIC cohort
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