循环胆红素水平与新诊断非增殖期糖尿病视网膜病变及其危险因素相关性的病例对照研究

Association of Circulating Bilirubin Levels with Newly Diagnosed Nonproliferative Diabetic Retinopathy and Its Related Risk Factors:A Case-control Study

【目的】本研究旨在评估循环胆红素谱[总胆红素(TBIL)、结合胆红素(DBIL)、未结合胆红素(IBIL)]与非增殖期糖尿病视网膜病变(NPDR)的相关性。【方法】采用病例对照研究设计,通过人工智能眼底相机对2型糖尿病患者视网膜病变情况进行筛查,并由眼科医生进一步阅片确认病例。最终纳入312名2型糖尿病(T2DM)患者(78例新诊断的NPDR患者与234例无糖尿病视网膜病变的T2DM患者进行1:3匹配)。同时收集患者人口学和相关临床资料,检测患者血清胆红素及相关生化指标。【结果】NPDR患者的TBIL、DBIL和IBIL浓度显著降低(P值分别为0.003、0.001、0.006),且与糖化血红蛋白(HbA1c)水平无关(P值均>0.05)。在调整了性别、糖尿病病程、HbA1c和收缩压等传统风险因素后,这种关联仍然存在。此外,在血糖控制良好的T2DM患者(HbA1c≤7%)或无微量白蛋白尿的T2DM患者[尿白蛋白/肌酐比值(UACR)≤30 mg/g]中,低水平未结合胆红素者的NPDR风险更高,比值比(OR)95%CI分别为3.44(1.04,11.38)和2.53(1.10,5.82);在血糖控制不良(HbA1c>7%)或有微量白蛋白尿(UACR>30 mg/g)的T2DM患者中,低水平结合胆红素者的NPDR风险更高,OR 95%CI分别为2.05(1.09,3.86)和2.40(1.14,5.02)。【结论】循环胆红素与NPDR的风险呈独立的负相关关系,这可能成为早期预测和防治糖尿病视网膜病变的临床生物标志物。

【Objective】This study aimed to assess the circulating bilirubin profile[total bilirubin(TBIL),conjugated bilirubin(DBIL),unconjugated bilirubin(IBIL)]and their associations with nonproliferative diabetic retinopathy(NPDR).【Methods】A case-control study which enrolled 312 type 2 diabetic mellitus(T2DM)patients(78 newly diagnosed NPDR 1:3 matched with 234 T2DM without diabetic retinopathy)was conducted. Diabetic retinopathy was screened by artificial intelligence fundus camera and further confirmed by the ophthalmologist,and demographic and clinical information were collected. Serum bilirubin and related biochemical indicators were assessed.【Results】Patients with NPDR had significantly lower serum TBIL,DBIL and IBIL concentrations(P values were 0.003,0.001 and 0.006),which were not associated with glycated hemoglobin(HbA1c)concentration(all P values >0.05). The association persisted after adjustment for traditional risk factors including gender,diabetes duration,HbA1c and systolic blood pressure. Moreover,low IBIL had a higher risk of NPDR with odds ratio(OR)95%CI of 3.44(1.04,11.38)in well glycemic controlled T2DM patients(HbA1c ≤7%) or of 2.53(1.10,5.82) in T2DM patients without microalbuminuria [urine albumin creatine ratio(UACR)≤30 mg/g];low DBIL had a higher risk of NPDR with OR 95%CI of 2.05(1.09,3.86)in poor glycemic controlled T2DM patients(HbA1c>7%)or of 2.40(1.14,5.02)in T2DM patients with microalbuminuria(UACR >30 mg/g).【Conclusion】Our results suggested that circulating bilirubin level is inversely and independently associated with NPDR which might be an early clinical biomarker for predicting and preventing diabetic retinopathy.