Schultz C J, Konopelska-Bahu T, Dalton R N, Carroll T A, Stratton I, Gale E A, Neil A, Dunger D B
Division of Public Health and Primary Health Care, University of Oxford, London, U.K.
Diabetes Care. 1999 Mar;22(3):495-502. doi: 10.2337/diacare.22.3.495.
The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes.
Between 1985 and 1996, 514 children (279 male) who developed type 1 diabetes before the age of 16 years (91% of those eligible from a region where ascertainment of new cases is 95%) were recruited for a longitudinal study with central annual assessment of HbAlc and albumin excretion (three urine samples). Dropout rates have been < 1% per year, and 287 children have been followed for > 4.5 years.
MA (defined as albumin-to-creatinine ratio > or = 3.5 and > or = 4.0 mg/mmol in boys and girls, respectively) developed in 63 (12.8%) and was persistent in 22 (4.8%) of the subjects. The cumulative probability (based on the Kaplan-Meier method) for developing MA was 40% after 11 years. HbAlc was worse in those who developed MA than in others (mean difference +/- SEM: 1.1% +/- 0.2, P < 0.001). In subjects who had been 5-11 years of age when their diabetes was diagnosed, the appearance of MA was delayed until puberty, whereas of those whose age was < 5 years at diagnosis of diabetes, 5 of 11 (45%) developed MA before puberty. The adjusted proportional probability (Cox model) of MA was greater for female subjects (200%), after pubertal onset (310%), and with greater HbAlc (36% increase for every 1% increase in HbAlc). Despite earlier differences based on age at diagnosis of diabetes (< 5, 5-11, and > 11 years), the overall cumulative risks in these groups were similar (38 vs. 29 vs. 39%, respectively) after 10 years' duration of diabetes.
Prepubertal duration of diabetes and prepubertal hyperglycemia contribute to the risk of postpubertal MA. The differences in rates of development of MA relating to HbAlc, sex, and age at diagnosis relative to puberty may have long-term consequences for the risk of subsequent nephropathy and for cardiovascular risk.
1型糖尿病患儿微量白蛋白尿（MA）的预测价值尚未明确。我们描述了一大群1型糖尿病确诊时招募的儿童中MA的自然病程。
1985年至1996年间，招募了514名16岁前患1型糖尿病的儿童（279名男性）（占一个新病例确诊率为95%的地区符合条件者的91%）进行纵向研究，每年集中评估糖化血红蛋白（HbAlc）和白蛋白排泄情况（采集三份尿液样本）。每年的失访率<1%，287名儿童随访时间>4.5年。
MA（分别定义为男孩白蛋白与肌酐比值≥3.5、女孩≥4.0mg/mmol）在63名（12.8%）受试者中出现，22名（4.8%）持续存在。根据Kaplan-Meier方法，11年后发生MA的累积概率为40%。发生MA者的HbAlc比未发生者更差（平均差值±标准误：1.1%±0.2，P<0.001）。糖尿病确诊时年龄为5-11岁的受试者，MA的出现延迟至青春期，而糖尿病确诊时年龄<5岁的受试者中，11名中有5名（45%）在青春期前发生MA。调整后的MA比例概率（Cox模型）在女性受试者中更高（200%），青春期开始后更高（310%），HbAlc越高也越高（HbAlc每升高1%增加36%）。尽管根据糖尿病确诊时的年龄（<5岁、5-11岁和>11岁）存在早期差异，但糖尿病病程10年后这些组的总体累积风险相似（分别为38%、29%和39%）。
青春期前糖尿病病程和青春期前高血糖会增加青春期后发生MA的风险。MA发生率与HbAlc、性别以及确诊时相对于青春期的年龄之间的差异，可能对随后肾病风险和心血管风险产生长期影响。
