中国与美国儿童青少年1型糖尿病患者发病年龄对生长发育的影响

Impact of onset age on the growth of children and adolescents with type 1 diabetes mellitus in China and America

目的探究中国湘雅二医院1型糖尿病(T1DM)数据集及美国T1DM交流注册(T1DX)数据集中儿童青少年T1DM患者发病年龄对生长发育的影响。方法利用中南大学湘雅二医院于2015年9月至2021年1月收集的536例,以及美国T1DX数据集于2010年9月至2012年8月收集的10963例18岁以下T1DM患者的首诊资料开展横断面研究。收集患者的性别、病程、糖化血红蛋白(HbA1c)水平、胰岛素治疗方式、糖尿病酮症酸中毒发生情况等,以世界卫生组织儿童生长发育评价标准计算不同性别受试者的年龄别身高Z评分(HAZ)和年龄别BMI Z评分(BMIZ)。利用限制性立方样条函数探究中美T1DM患者发病年龄与HAZ的非线性关系。基于非线性研究结果根据发病年龄分别对中美两组研究对象进行分组(<10岁组和≥10岁组),组间比较采用t检验、Wilcoxon秩和检验或χ^(2)检验。进一步采用多元线性回归模型探究病程、BMIZ、HbA1c水平、胰岛素治疗方式、糖尿病酮症酸中毒发生情况等因素对患者生长发育的潜在影响。结果4.67%(25/536)的中国湘雅二医院T1DM数据集患者及1.67%(183/10936)的美国T1DX数据集患者出现生长发育迟滞(HAZ<-2SD)(P<0.001)。中美两个数据集儿童青少年T1DM患者中,发病年龄与HAZ呈倒U型关系,以10岁左右为拐点。校正性别、年龄、病程、HbA1c、胰岛素治疗方式、糖尿病酮症酸中毒发生情况等因素后,在发病年龄≥10岁组中,发病年龄与HAZ呈负相关(中国湘雅:β=-0.191,P<0.001;美国T1DX:β=-0.039,P<0.001);发病年龄<10岁组中发病年龄与HAZ呈现正相关关系,但中国湘雅二医院T1DM数据集患者未达到统计学意义(美国T1DX:β=0.056,P<0.001;中国湘雅:P=0.315)。发病年龄≥10岁患者中,美国T1DX数据集患者的HAZ与病程、BMIZ、HbA1c等显著相关(β=-0.041、0.135、-0.035,均P<0.001);中国湘雅T1DM患者的HAZ仅与BMIZ相关(β=0.176,P=0.027)。结论发病年龄是影响中美儿童青少年T1DM患者生长发育的关键因素,两者呈倒U型曲线关系,以10岁左右发病为拐点。

Objective To investigate the association between age at onset of type 1 diabetes mellitus(T1DM)and growth in pediatric T1DM subjects from the Second Xiangya Hospital of China and the T1DM Exchange Registry(T1DX)of America.Methods We conducted a cross-sectional study using first visit data from 536 Chinese T1DM cases(age≤18 years old)collected by the Second Xiangya Hospital of Central South University between September 2015 and January 2021,and 10963 American T1DM cases(age≤18 years old)collected by the T1DX between September 2010 and August 2012.Gender,disease course,glycated hemoglobin A1c(HbA1c)level,insulin treatment,and incidence of diabetic ketoacidosis were collected.The age-specific height Z score(HAZ)and age-specific BMI Z score(BMIZ)of the subjects of different sexes were calculated according to the World Health Organization child growth and development evaluation criteria.The restricted cubic spline models were used to analyze the non-linear relationships between the age at onset and HAZ in children and adolescents with T1DM from China and America.Based on the non-linear research results,the Chinese and American subjects were divided into different groups according to the age of T1DM onset(<10 years group and≥10 years group).Comparisons between groups were performed by t test,Wilcoxon rank sum test andχ^(2) test.Multiple linear regression models were also used to explore the potential effects of disease course,BMIZ,insulin treatment and occurrence of diabetic ketoacidosis on the growth of patients.Results Growth retardation was present in 25 of 536(4.67%)Chinese patients with T1DM and 183 of 10936(1.67%)American patients(P<0.001).Inverted U-shaped relationships between age at onset and HAZ score were observed in both cohorts,with minimal effects at the onset age of 10 years.Clear negative associations between age at onset and HAZ were observed in patients with age at onset≥10 years in both country cohorts(Chinese:β=-0.191,P<0.001;American:β=-0.039,P<0.001),whereas a positive association was only found in American patients with age at onset<10 years(American:β=0.056,P<0.001;Chinese:P=0.315),after controlling for potential confounders.Furthermore,multivariable regression analysis showed that T1DM duration,BMIZ and HbA1c were significantly associated with HAZ in American subjects with T1DM(β=-0.041,0.135,-0.035,all P<0.001),but only BMIZ was marginally associated with HAZ in Chinese Xiangya subjects(β=-0.176,P=0.027).Conclusions Age at onset is the most important factor influencing linear growth in children with T1DM.Inverted U-shaped curves were found for the association between age at onset of T1DM and HAZ in both Chinese and American cohorts,with a turning point in the age at onset at around 10 years.