Division of Endocrinology and Metabolism, University of Toronto, Toronto, Canada.
Biostatistics Center, The George Washington University, Rockville, MD.
Diabetes Care. 2019 May;42(5):883-890. doi: 10.2337/dc18-2062. Epub 2019 Mar 4.
In type 1 diabetes (T1D), the course of microalbuminuria is unpredictable and timing of glomerular filtration rate (GFR) loss is uncertain. Thus, there is a need to identify the risk factors associated with the development of more advanced stages of kidney disease through large, long-term systematic analysis.
Multivariable Cox proportional hazards models assessed the association of baseline and time-dependent glycemic and nonglycemic risk factors for incident macroalbuminuria and reduced estimated GFR (eGFR; defined as <60 mL/min/1.73 m) over a mean of 27 years in the Diabetes Control and Complications Trial (DCCT) cohort.
Higher mean HbA (hazard ratio [HR] 1.969 per 1% higher level [95% CI 1.671-2.319]) and male sex (HR 2.767 [95% CI 1.951-3.923]) were the most significant factors independently associated with incident macroalbuminuria, whereas higher mean triglycerides, higher pulse, higher systolic blood pressure (BP), longer diabetes duration, higher current HbA, and lower mean weight had lower magnitude associations. For incident reduced eGFR, higher mean HbA (HR 1.952 per 1% higher level [95% CI 1.714-2.223]) followed by higher mean triglycerides, older age, and higher systolic BP were the most significant factors.
Although several risk factors associated with macroalbuminuria and reduced eGFR were identified, higher mean glycemic exposure was the strongest determinant of kidney disease among the modifiable risk factors. These findings may inform targeted clinical strategies for the frequency of screening, prevention, and treatment of kidney disease in T1D.
在 1 型糖尿病(T1D)中,微量白蛋白尿的病程不可预测,肾小球滤过率(GFR)丧失的时间也不确定。因此,需要通过大型、长期的系统分析来确定与更严重肾脏疾病发展相关的风险因素。
多变量 Cox 比例风险模型评估了基线和时间依赖性血糖和非血糖危险因素与糖尿病控制和并发症试验(DCCT)队列中平均 27 年时间内发生大量白蛋白尿和估算肾小球滤过率(eGFR;定义为 <60 mL/min/1.73 m)降低的相关性。
较高的平均 HbA(每升高 1%的风险比 [HR] 为 1.969[95%CI 1.671-2.319])和男性(HR 为 2.767[95%CI 1.951-3.923])是与发生大量白蛋白尿最显著的独立相关因素,而较高的平均甘油三酯、较高的脉搏、较高的收缩压(BP)、较长的糖尿病病程、较高的当前 HbA 和较低的平均体重与较低的关联幅度相关。对于发生 eGFR 降低,较高的平均 HbA(每升高 1%的 HR 为 1.952[95%CI 1.714-2.223])紧随其后的是较高的平均甘油三酯、年龄较大和较高的收缩压。
尽管确定了与大量白蛋白尿和 eGFR 降低相关的几个危险因素,但较高的平均血糖暴露是可改变危险因素中导致肾脏疾病的最强决定因素。这些发现可能为 T1D 中肾脏疾病的筛查、预防和治疗的靶向临床策略提供信息。