正常但不断升高的糖化血红蛋白水平预示着从胰岛自身免疫进展为显性1型糖尿病：青少年糖尿病自身免疫研究（DAISY）。

Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY).

作者信息

Stene Lars C, Barriga Katherine, Hoffman Michelle, Kean Jaime, Klingensmith Georgeanna, Norris Jill M, Erlich Henry A, Eisenbarth George S, Rewers Marian

机构信息

Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045-6511, USA.

出版信息

Pediatr Diabetes. 2006 Oct;7(5):247-53. doi: 10.1111/j.1399-5448.2006.00198.x.

DOI:10.1111/j.1399-5448.2006.00198.x

PMID:17054445

Abstract

OBJECTIVE

The aim of this study was to assess the utility of hemoglobin A1c (HbA1c) measurements in the early detection of clinical type 1 diabetes during prospective follow-up of children with islet autoimmunity.

METHODS

The Diabetes Autoimmunity Study in the Young (DAISY) has followed for development of islet autoimmunity and diabetes general population newborns carrying human leukocyte antigen (HLA) genotypes conferring risk for type 1 diabetes and young siblings or offspring of people with type 1 diabetes. Testing for autoantibodies was performed at least once in 2234 and twice or more in 1887 children. Among the latter, 100 children tested positive on at least two consecutive visits. To date, 92 children have developed persistent islet autoantibodies to glutamic acid decarboxylase 65 (GAD65), insulin, or insulinoma associated antigen-2 (IA-2) and had at least two subsequent clinic visits. These children had study visits with point-of-care testing for HbA1c and random glucose every 3-6 months and those with random plasma glucose above 11.1 mmol/L or HbA1c above 6.3% were evaluated by a pediatric endocrinologist for clinical diabetes.

RESULTS

During a mean follow-up of 3.4 yr from onset of autoimmunity, 28 children developed type 1 diabetes, at mean age of 6.5 yr. Mean prediagnostic HbA1c was 5.1% [standard deviation (SD) = 0.4%]. In a Cox regression model accounting for changes in values in individuals over time, increase in HbA1c predicted increased risk of progression to type 1 diabetes, hazard ratio = 4.8 (95% confidence interval 3.0-7.7) for each SD of 0.4%, independent of random glucose and number of autoantibodies. Increase in random plasma glucose levels only marginally predicted risk of progression (hazard ratio = 1.4, 95% confidence interval 1.02-1.8, per SD of 1.1 mmol/L).

CONCLUSIONS

Normal but increasing Hb1Ac may be useful in early detection of type 1 diabetes, whereas random plasma glucose levels were less predictive.

摘要

目的

本研究旨在评估在对患有胰岛自身免疫的儿童进行前瞻性随访期间，糖化血红蛋白（HbA1c）检测在临床1型糖尿病早期检测中的效用。

方法

青少年糖尿病自身免疫研究（DAISY）对携带赋予1型糖尿病风险的人类白细胞抗原（HLA）基因型的普通人群新生儿以及1型糖尿病患者的年轻兄弟姐妹或后代进行胰岛自身免疫和糖尿病发展情况的随访。对2234名儿童至少进行了一次自身抗体检测，对1887名儿童进行了两次或更多次检测。在后者中，100名儿童在至少连续两次就诊时检测呈阳性。迄今为止，92名儿童已产生针对谷氨酸脱羧酶65（GAD65）、胰岛素或胰岛素瘤相关抗原2（IA-2）的持续性胰岛自身抗体，并随后至少进行了两次门诊就诊。这些儿童每3 - 6个月进行一次糖化血红蛋白即时检测和随机血糖检测，随机血浆葡萄糖高于11.1 mmol/L或糖化血红蛋白高于6.3%的儿童由儿科内分泌学家评估是否患有临床糖尿病。

结果

在自身免疫发病后的平均3.4年随访期间，28名儿童患1型糖尿病，平均年龄为6.5岁。诊断前糖化血红蛋白的平均值为5.1% [标准差（SD）= 0.4%]。在一个考虑个体随时间变化值的Cox回归模型中，糖化血红蛋白的升高预示着进展为1型糖尿病的风险增加，每0.4%标准差的风险比为4.8（95%置信区间3.0 - 7.7），与随机血糖和自身抗体数量无关。随机血浆葡萄糖水平的升高仅略微预示进展风险（风险比 = 1.4，95%置信区间1.02 - 1.8，每1.1 mmol/L标准差）。