Xie Yan, Bowe Benjamin, Li Tingting, Xian Hong, Al-Aly Ziyad
1 Clinical Epidemiology Center, Research and Education Service, VA St Louis Health Care System, St Louis, MO, USA.
2 Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Diab Vasc Dis Res. 2018 Sep;15(5):409-416. doi: 10.1177/1479164118785050. Epub 2018 Jul 5.
Laboratory evidence suggests that urea suppresses insulin secretion and sensitivity. Emerging epidemiologic evidence suggests that higher levels of urea are associated with increased risk of incident diabetes mellitus. However, whether elevated levels of blood urea nitrogen are associated with increased risk of insulin use among people with diabetes is unknown. We used the Department of Veterans Affairs databases to assemble a cohort of 197,994 incident users of non-insulin hypoglycaemic agents with an estimated glomerular filtration rate > 60 mL/min per 1.73 m and followed them for a median of 4.93 years. Spline analyses suggested that the relationship between blood urea nitrogen and the risk of insulin use was neutral below blood urea nitrogen level of 25 mg/dL and increased exponentially with blood urea nitrogen levels above 25 mg/dL. In survival models, compared to those with blood urea nitrogen ⩽ 25 mg/dL, those with blood urea nitrogen > 25 mg/dL had an increased risk of insulin use (hazard ratio = 1.40; confidence interval = 1.30-1.50). The risk of insulin use was increased in models which accounted for haemoglobin A1c at time zero (hazard ratio = 1.39; confidence interval = 1.28-1.50) and as a time-varying variable (hazard ratio = 1.38; confidence interval = 1.28-1.50). Two-step residual estimation analyses showed that, independent of the impact of estimated glomerular filtration rate, every 10-mg/dL increase in blood urea nitrogen concentration was associated with increased risk of insulin use (hazard ratio = 1.16; confidence interval = 1.12-1.20). Our results suggest that, among people with diabetes, higher levels of blood urea nitrogen are associated with an increased risk of insulin use.
实验室证据表明，尿素会抑制胰岛素分泌及敏感性。新出现的流行病学证据表明，较高水平的尿素与新发糖尿病风险增加有关。然而，糖尿病患者血尿素氮水平升高是否与胰岛素使用风险增加相关尚不清楚。我们利用退伍军人事务部数据库，纳入了197994名新使用非胰岛素降糖药、估计肾小球滤过率>60 mL/（min·1.73 m²）的患者队列，并对他们进行了中位时间为4.93年的随访。样条分析表明，血尿素氮水平低于25 mg/dL时，其与胰岛素使用风险之间的关系呈中性，而血尿素氮水平高于25 mg/dL时，二者风险呈指数增长。在生存模型中，与血尿素氮≤25 mg/dL的患者相比，血尿素氮>25 mg/dL的患者胰岛素使用风险增加（风险比=1.40；置信区间=1.30-1.50）。在将零时间糖化血红蛋白作为变量（风险比=1.39；置信区间=1.28-1.50）以及作为随时间变化的变量（风险比=1.38；置信区间=1.28-1.50）的模型中，胰岛素使用风险均增加。两步残差估计分析表明，在不考虑估计肾小球滤过率影响的情况下，血尿素氮浓度每升高10 mg/dL，胰岛素使用风险增加（风险比=1.16；置信区间=1.12-1.20）。我们的研究结果表明，糖尿病患者中，较高的血尿素氮水平与胰岛素使用风险增加相关。
