OBJECTIVE Sustained excess BMI increases the risk of type 1 diabetes (T1D) in autoantibody-positive relatives without diabetes of patients. We tested whether elevated BMI also accelerates the progression of islet autoimmunity before T1D diagnosis. RESEARCH DESIGN AND METHODS We studied 706 single autoantibody-positive pediatric TrialNet participants (ages 1.6-18.6 years at baseline). Cumulative excess BMI (ceBMI) was calculated for each participant based on longitudinally accumulated BMI ≥85th age- and sex-adjusted percentile. Recursive partitioning analysis and multivariable modeling defined the age cut point differentiating the risk for progression to multiple positive autoantibodies. RESULTS At baseline, 175 children (25%) had a BMI ≥85th percentile. ceBMI range was -9.2 to 15.6 kg/m2 (median -1.91), with ceBMI ≥0 kg/m2 corresponding to persistently elevated BMI ≥85th percentile. Younger age increased the progression to multiple autoantibodies, with age cutoff of 9 years defined by recursive partitioning analysis. Although ceBMI was not significantly associated with progression from single to multiple autoantibodies overall, there was an interaction with ceBMI ≥0 kg/m2, age, and HLA (P = 0.009). Among children ≥9 years old without HLA DR3-DQ2 and DR4-DQ8, ceBMI ≥0 kg/m2 increased the rate of progression from single to multiple positive autoantibodies (hazard ratio 7.32, P = 0.004) and conferred a risk similar to that in those with T1D-associated HLA haplotypes. In participants <9 years old, the effect of ceBMI on progression to multiple autoantibodies was not significant regardless of HLA type. CONCLUSIONS These data support that elevated BMI may exacerbate islet autoimmunity prior to clinical T1D, particularly in children with lower risk based on age and HLA. Interventions to maintain normal BMI may prevent or delay the progression of islet autoimmunity.

中文翻译：

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体重指数过高会加速大龄儿童和青少年的胰岛自身免疫性。

目的持续过量的BMI会增加未患糖尿病的自身抗体阳性亲戚的1型糖尿病（T1D）风险。在T1D诊断之前，我们测试了BMI升高是否还加速了胰岛自身免疫的进程。研究设计和方法我们研究了706名单抗自身抗体阳性的儿科TrialNet参与者（基线年龄1.6-18.6岁）。根据纵向累积的BMI≥85岁和性别调整的百分位数，为每个参与者计算累积的过量BMI（ceBMI）。递归分区分析和多变量建模定义了年龄切入点，从而区分了发展为多种阳性自身抗体的风险。结果基线时，有175名儿童（25％）的BMI≥85％。ceBMI范围为-9.2至15.6 kg / m2（中位数-1.91），ceBMI≥0kg / m2对应于BMI持续升高≥85％。年龄越小，向多种自身抗体的进展就越多，通过递归分区分析确定的年龄界限为9岁。尽管ceBMI与从单个抗体到多个自身抗体的进展没有显着相关性，但与ceBMI≥0kg / m2，年龄和HLA相互作用（P = 0.009）。在没有HLA DR3-DQ2和DR4-DQ8且≥9岁的儿童中，ceBMI≥0kg / m2增加了从单一阳性抗体向多个阳性自身抗体的进展速度（危险比7.32，P = 0.004），并赋予了与具有T1D相关HLA单倍型的人。在<9岁的参与者中，无论HLA类型如何，ceBMI对进展为多种自身抗体的影响均不显着。结论这些数据支持BMI升高可能会在临床T1D之前加重胰岛自身免疫性，特别是对于年龄和HLA风险较低的儿童。维持正常BMI的干预措施可能会阻止或延迟胰岛自身免疫性疾病的进展。