胰岛自身免疫和 1 型糖尿病在遗传风险儿童中的生长和发育。
Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk.
机构信息
Department of Nutrition, Georgia State University, Atlanta, GA, USA.
Welfare and Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
出版信息
Diabetologia. 2021 Apr;64(4):826-835. doi: 10.1007/s00125-020-05358-3. Epub 2021 Jan 21.
AIMS/HYPOTHESIS: We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes.
METHODS
Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10-14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05.
RESULTS
In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2-10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling.
CONCLUSIONS/INTERPRETATION: In children at genetic risk of type 1 diabetes, being overweight at 2-10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00179777.
目的/假设：我们旨在评估儿童生长指标与胰岛自身免疫（IA）和 1 型糖尿病风险之间的关系，这些儿童存在一级亲属受累和 HLA 相关风险增加的情况。我们假设儿童期超重或肥胖与 IA 和 1 型糖尿病的风险增加有关。
方法
在一项随机婴儿喂养试验（N=2149）中，参与者每隔 12 个月测量体重和身长/身高，并从出生到 10-14 岁时进行 IA（至少有一个胰岛素自身抗体、胰岛抗原-2 自身抗体、GAD 自身抗体和锌转运蛋白 8 自身抗体阳性）和 1 型糖尿病的发展情况进行随访。在这项二次分析中，使用出生体重和身长 Z 分数、性别、HLA 风险、母亲 1 型糖尿病、分娩方式和母乳喂养持续时间进行 Cox 比例风险回归模型调整，并按居住地区（澳大利亚、加拿大、北欧、南欧、中欧和美国）进行分层。通过时间变化的 Cox 比例风险回归和联合建模来研究纵向暴露。使用 0.05 的全家族错误率考虑多重测试。
结果
在遗传危险的 1 型糖尿病减少试验（TRIGR）人群中，305 例（14.2%）发生 IA，172 例（8%）发生 1 型糖尿病。在 10 岁时，超重（包括肥胖）和肥胖儿童的比例分别为 28%和 9%。年度生长指标与 IA 无关，但 2-10 岁时超重与 1 型糖尿病的发生风险增加两倍相关（时间变化 Cox 回归的 HR 2.39；95%CI 1.46，3.92；p<0.001），联合建模也有类似的结果。
结论/解释：在 1 型糖尿病遗传风险的儿童中，2-10 岁时超重与从多种 IA 进展为 1 型糖尿病和 1 型糖尿病的发生风险增加有关，但与 IA 的发生无关。未来的研究应评估体重管理策略对这些结果的影响。
试验注册
ClinicalTrials.gov NCT00179777。
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