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新发儿童1型糖尿病部分临床缓解缺失的预测模型

A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes.

作者信息

Marino Katherine R, Lundberg Rachel L, Jasrotia Aastha, Maranda Louise S, Thompson Michael J, Barton Bruce A, Alonso Laura C, Nwosu Benjamin Udoka

机构信息

Division of Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

出版信息

PLoS One. 2017 May 1;12(5):e0176860. doi: 10.1371/journal.pone.0176860. eCollection 2017.

Abstract

IMPORTANCE

50% of patients with new-onset type 1 diabetes (T1D) do not enter partial clinical remission (PCR); early identification of these patients may improve initial glycemic control and reduce long-term complications.

AIM

To determine whether routinely obtainable clinical parameters predict non-remission in children and adolescents with new-onset T1D.

SUBJECTS AND METHODS

Data on remission were collected for the first 36 months of disease in 204 subjects of ages 2-14 years with new-onset type 1 diabetes. There were 86 remitters (age 9.1±3.0y; male 57%), and 118 non-remitters (age 7.0±3.1y; male 40.7%). PCR was defined as insulin-dose adjusted hemoglobin A1c of ≤9.

RESULTS

Non-remission occurred in 57.8% of subjects. Univariable analysis showed that the risk for non-remission was increased 9-fold in patients with 4 diabetes-associated auto-antibodies (OR = 9.90, p = 0.010); 5-fold in patients <5 years old (odds ratio = 5.38, p = 0.032), 3-fold in those with bicarbonate of <15 mg/dL at diagnosis (OR = 3.71, p = 0.008). Combined estimates of risk potential for HC03 and the number of autoantibodies by multivariable analysis, adjusted for BMI standard deviation score, showed HC03 <15 mg/dL with a clinically significant 10-fold risk (OR = 10.1, p = 0.074); and the number of autoantibodies with a 2-fold risk for non-remission (OR = 1.9, p = 0.105). Male sex and older age were associated with decreased risk for non-remission. A receiver-operating characteristic curve model depicting sensitivity by 1-specificity for non-remission as predicted by bicarbonate <15 mg/dL, age <5y, female sex, and >3 diabetes-associated autoantibodies had an area under the curve of 0.73.

CONCLUSIONS

More than 50% of children and adolescents with new-onset T1D do not undergo partial clinical remission and are thus at an increased risk for long-term complications of diabetes mellitus. A predictive model comprising of bicarbonate <15 mg/dL, age <5y, female sex, and >3 diabetes-associated autoantibodies has 73% power for correctly predicting non-remission in children and adolescents with new-onset T1D. Early identification of these non-remitters may guide the institution of targeted therapy to limit dysglycemia and reduce the prevalence of long-term deleterious complications.

摘要

重要性

超过50%的新发1型糖尿病(T1D)患者未进入部分临床缓解(PCR)状态;早期识别这些患者可能改善初始血糖控制并减少长期并发症。

目的

确定常规可获取的临床参数是否能预测新发T1D儿童和青少年的未缓解情况。

研究对象与方法

收集了204例年龄在2至14岁的新发1型糖尿病患者疾病最初36个月的缓解数据。其中有86例缓解者(年龄9.1±3.0岁;男性占57%),118例未缓解者(年龄7.0±3.1岁;男性占40.7%)。PCR定义为胰岛素剂量调整后的糖化血红蛋白A1c≤9。

结果

57.8%的受试者未出现缓解。单因素分析显示,具有4种糖尿病相关自身抗体的患者未缓解风险增加9倍(OR = 9.90,p = 0.010);5岁以下患者风险增加5倍(比值比 = 5.38,p = 0.032),诊断时碳酸氢盐水平<15 mg/dL的患者风险增加3倍(OR = 3.71,p = 0.008)。通过多因素分析对风险潜力进行联合估计,校正体重指数标准差评分后,显示碳酸氢盐<15 mg/dL具有临床上显著的10倍风险(OR = 10.1,p = 0.074);自身抗体数量使未缓解风险增加2倍(OR = 1.9,p = 0.105)。男性和年龄较大与未缓解风险降低相关。以碳酸氢盐<15 mg/dL、年龄<5岁、女性性别以及>3种糖尿病相关自身抗体预测未缓解情况的受试者工作特征曲线模型,曲线下面积为0.73。

结论

超过50%的新发T1D儿童和青少年未经历部分临床缓解,因此患糖尿病长期并发症的风险增加。由碳酸氢盐<15 mg/dL、年龄<5岁、女性性别以及>3种糖尿病相关自身抗体组成的预测模型,正确预测新发T1D儿童和青少年未缓解情况的能力为73%。早期识别这些未缓解者可能指导实施靶向治疗,以限制血糖异常并降低长期有害并发症的发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5043/5411061/59dfbe0d850c/pone.0176860.g002.jpg

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