Moon Shinje, Yoo Hyung-Joon, Ahn You-Hern, Kim Gheun-Ho, Yu Jae Myung, Park Joon-Sung
Department of Internal Medicine, Hallym University College of Medicine Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.
Medicine (Baltimore). 2018 Jan;97(3):e9351. doi: 10.1097/MD.0000000000009351.
The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regression analysis was constructed to evaluate the association between DR and related clinical parameters, including urinary albumin-creatinine ratio (UACR, mg/g creatinine). The biological interaction of glycemic status and UACR on DR was evaluated by 3 indices: RERI, the relative excess risk due to the interaction; AP, the attributable proportion due to the interaction; and S, the additive interaction index of synergy.We found that UACR, glycated hemoglobin (HbA1c), and diabetic duration were deeply associated with increased risk of DR (UACR, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02-1.07; HbA1c, OR = 1.16, 95% CI = 1.04-1.30; diabetic duration, OR = 1.06, 95% CI = 1.04-1.07). Furthermore, our interaction analysis demonstrated that synergistic interaction between HbA1c and UACR on development of DR was prominent in participants with diabetic duration of ≥10 years (adjusted RERI = 0.92, 95% CI = 0.10-1.74; adjusted AP = 0.29, 95% CI = -0.82-1.41; adjusted S = 1.76, 95% CI = 1.27-2.25), but not subjects with shorter diabetic duration.These findings imply that there is the interaction between prolonged hyperglycemic exposure and increased urinary albumin excretion may exert additive synergistic effect on vascular endothelial dysfunction in the eye, even before the appearance of overt diabetic nephropathy.
在临床研究中，尿白蛋白排泄轻度增加与糖尿病视网膜病变（DR）之间的关联存在争议。本研究旨在阐明血糖暴露增加与尿白蛋白排泄轻度增加之间的相互作用对DR风险的影响。数据收集自2005年至2012年的美国国家健康与营养检查调查（NHANES）。总体而言，对953名无微量白蛋白尿的参与者（477名男性和476名女性）的数据进行了评估。构建逻辑回归分析以评估DR与相关临床参数之间的关联，包括尿白蛋白肌酐比值（UACR，mg/g肌酐）。通过3个指标评估血糖状态和UACR对DR的生物学相互作用：RERI，即由于相互作用导致的相对超额风险；AP，即由于相互作用导致的归因比例；以及S，即协同作用的相加相互作用指数。我们发现，UACR、糖化血红蛋白（HbA1c）和糖尿病病程与DR风险增加密切相关（UACR，比值比[OR]=1.04，95%置信区间[CI]=1.02-1.07；HbA1c，OR=1.16，95%CI=1.04-1.30；糖尿病病程，OR=1.06，95%CI=1.04-1.07）。此外，我们的相互作用分析表明，在糖尿病病程≥10年的参与者中，HbA1c和UACR对DR发生的协同相互作用较为显著（调整后的RERI=0.92，95%CI=0.10-1.74；调整后的AP=0.29，95%CI=-0.82-1.41；调整后的S=1.76，95%CI=1.27-2.25），而在糖尿病病程较短的受试者中则不显著。这些发现表明，即使在明显的糖尿病肾病出现之前，长期高血糖暴露与尿白蛋白排泄增加之间的相互作用可能会对眼部血管内皮功能障碍产生相加协同效应。
