Department of Nutrition, Georgia State University, Atlanta, GA, USA.
Welfare and Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
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.
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.
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.
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。
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。
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。
ClinicalTrials.gov NCT00179777。
