无高尿酸血症的2型糖尿病患者血尿酸水平与新发心血管事件密切相关:基于10年多中心队列研究

Serum uric acid level is associated with the incidence of cardiovascular events in patients with type 2 diabetes mellitus without hyperuricemia:based on a 10-year multicenter cohort study

目的探讨无高尿酸血症的2型糖尿病(T_(2)DM)患者血尿酸(SUA)水平对新发大血管事件的影响。方法本研究基于北京社区糖尿病研究(BCDS)队列,自2008年8月至2009年7月,通过整群随机抽样法纳入来自北京市5个城区25个社区卫生服务中心的受试者,选择其中完成10年随访的2988例基线无高尿酸血症的T_(2)DM患者作为研究对象。收集研究对象的一般资料及实验室检查结果,新发大血管事件(心血管事件、脑血管事件、周围血管事件)由专家诊断评估小组进行审核。总人群和不同性别受试者分别根据基线SUA水平三分位数进行分组(T_(1)、T_(2)和T_(3)组)。组间比较采用方差分析、Kruskal-Wallis H检验和χ^(2)检验。应用Cox回归分析法分析基线SUA水平与新发大血管事件的关系。结果总人群中,T_(1)组(SUA≤252.00μmol/L)1005例,T_(2)组(252.00μmol/L<SUA≤315.07μmol/L)988例,T_(3)组(SUA>315.07μmol/L)995例。男性中,T_(1)组(SUA≤266.33μmol/L)404例,T_(2)组(266.33μmol/L<SUA≤332.22μmol/L)405例,T_(3)组(SUA>332.22μmol/L)404例。女性中,T_(1)组(SUA≤242.00μmol/L)594例,T_(2)组(242.00μmol/L<SUA≤305.00μmol/L)592例,T_(3)组(SUA>305.00μmol/L)589例。在总体及男女人群中,随着SUA水平的增加,新发心血管事件显著增加,差异均具有统计学意义(P<0.05),新发脑血管事件差异无统计学意义(P>0.05),而新发周围血管事件发生率在总人群T_(3)组最高(P=0.044)。Cox回归分析结果显示,在总人群中,校正性别、年龄、糖尿病病程、体重指数、腰围、血压、糖化血红蛋白、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、估算的肾小球滤过率、降糖方案、家庭人均月收入、教育程度、吸烟状态后,与T_(1)组相比,T_(3)组心血管事件发生风险显著增加(HR=1.998,95%CI 1.380~2.893,P<0.001);进一步按性别分组,校正上述混杂因素后,无论在男性还是女性中,与T_(1)组相比,T_(2)和T_(3)组心血管事件发生风险均显著增加(P<0.05)。在总体及男女人群,校正上述混杂因素后,随着SUA三分位数增加,脑血管事件和周围血管事件发生风险均无显著增加(P>0.05)。结论无高尿酸血症的T_(2)DM患者SUA水平是新发心血管事件的独立影响因素,提示T_(2)DM患者即使SUA水平在正常范围,较高的SUA仍可预测心血管事件的发生风险。

Objective To investigate the effect of baseline serum uric acid(SUA)on the incidence of macrovascular events in patients with type 2 diabetes mellitus(T_(2)DM)without hyperuricemia.Methods Based on a ten-year cohort of Beijing Community Diabetes Study,using cluster random sampling,participants from 25 communities of 5 districts of Beijing were selected between August 2008 and July 2009.A total of 2988 T_(2)DM patients without hyperuricemia who completed 10-year follow-up were included.The clinical information was collected at baseline,and the occurrence of macrovascular events(cardiovascular events,cerebrovascular events,peripheral vascular events)were adjudicated by the expert diagnosis group.The total,male and female populations were divided into three groups according to the baseline SUA tertiles(T_(1),T_(2),and T_(3)group),respectively.Differences among three groups were evaluated by one-way analysis of variance(ANOVA)or Kruskal-Wallis H test orχ^(2) test.Cox regression analyses were applied to evaluate the relationship between the SUA tertiles and the risks of macrovascular events.Results In the total population,the T_(1)group(SUA≤252.00μmol/L)consisted of 1005 cases,T_(2)group(252.00μmol/L<SUA≤315.07μmol/L)consisted of 988 cases,and T_(3)group(SUA>315.07μmol/L)consisted of 995 cases.In the male population,T_(1)group(SUA≤266.33μmol/L)included 404 cases,T_(2)group(266.33μmol/L<SUA≤332.22μmol/L)included 405 cases,and T_(3)group(SUA>332.22μmol/L)included 404 cases.In the female population,T_(1)group(SUA≤242.00μmol/L)included 594 cases,T_(2)group(242.00μmol/L<SUA≤305.00μmol/L)included 592 cases,and T_(3)group(SUA>305.00μmol/L)included 589 cases.In total,male and female populations,the incidence of cardiovascular events increased with the increasing of SUA level,and the difference among the three SUA tertiles groups was statistically significant(P<0.05),while there was no significant difference in the incidence of cerebrovascular events(P>0.05),and the incidence of peripheral vascular events was highest in T_(3)group of the total population(P=0.044).In total population,compared with the T_(1)group,Cox regression analysis indicated that the T_(3)group had a significantly increased risk of cardiovascular events(HR=1.998,95%CI 1.380-2.893,P<0.001)after adjustments for gender,age,body mass index,waist circumference,blood pressure,duration of diabetes,glycated hemoglobin A1c,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,estimated glomerular filtration rate,anti-hyperglycemic therapy,income,education level and smoking habits.After stratification by gender,the risk of cardiovascular events was also significantly increased in T_(2)and T_(3)groups compared with those in T_(1)groups in male and female(P<0.05).In total,male and female populations,the incidences of cerebrovascular events and peripheral vascular events were not significantly associated with the SUA tertiles after adjustment for multiple factors(P>0.05).Conclusions The SUA level was independently associated with the risk of cardiovascular events in the patients with T_(2)DM even without hyperuricemia,suggesting that higher level of SUA may predict the new occurrence of cardiovascular events in T_(2)DM patients with SUA levels in the normal range.