Winkler C, Marienfeld S, Zwilling M, Bonifacio E, Ziegler A-G
Institut für Diabetesforschung der Forschergruppe Diabetes e.V., Helmholtz Center Munich, Neuherberg, Germany.
Diabetologia. 2009 Oct;52(10):2072-8. doi: 10.1007/s00125-009-1461-1. Epub 2009 Jul 30.
AIMS/HYPOTHESIS: It has been suggested that metabolic demand and insulin resistance play a role in the development of type 1 diabetes, including the onset of autoimmunity. The aim of the present study was to determine whether insulin demand is increased in children with islet autoantibodies.
BMI standard deviation score (BMI-SDS) was measured from 2 years of age in 1,650 prospectively followed children of mothers or fathers with type 1 diabetes, including 135 who developed persistent islet autoantibodies. HOMA of insulin resistance (HOMA-IR) was determined using fasting samples from 777 of the children starting from age 5 years.
An increased HOMA-IR was associated with female sex (p = 0.0004), older age (p < 0.0001) and increased BMI-SDS (p < 0.0001). Children with islet autoantibodies did not have an increased HOMA-IR compared with age-matched islet autoantibody-negative children (age 8 years: mean 0.61 vs mean 0.72, respectively, p = 0.21; age 11 years: mean 0.96 vs mean 1.21, respectively, p = 0.07). Furthermore, after correction for age and sex, autoantibody positivity was associated with decreased HOMA-IR values (p = 0.01). BMI-SDS was similar between islet autoantibody-positive and -negative children at age 2 (mean 0.07 vs mean 0.16, respectively), 5 (mean 0.06 vs 0.08, respectively), 8 (mean - 0.09 vs mean 0.02, respectively), and 11 years (mean 0.22 vs mean 0.16, respectively) and similar to that of national reference values.
CONCLUSIONS/INTERPRETATION: Islet autoantibody-positive children in the BABYDIAB cohort are not insulin resistant and do not have an increased BMI around and early after islet autoantibody seroconversion. These findings are inconsistent with the notion that insulin resistance is a risk factor for islet autoimmunity.
目的/假设：有人提出，代谢需求和胰岛素抵抗在1型糖尿病的发生发展中起作用，包括自身免疫的发作。本研究的目的是确定胰岛自身抗体阳性儿童的胰岛素需求是否增加。
对1650名母亲或父亲患有1型糖尿病的前瞻性随访儿童从2岁起测量体重指数标准差评分（BMI-SDS），其中135名儿童出现持续性胰岛自身抗体。从5岁起，对777名儿童的空腹样本测定胰岛素抵抗的稳态模型评估（HOMA-IR）。
HOMA-IR升高与女性性别（p = 0.0004）、年龄较大（p < 0.0001）和BMI-SDS升高（p < 0.0001）相关。与年龄匹配的胰岛自身抗体阴性儿童相比，胰岛自身抗体阳性儿童的HOMA-IR没有升高（8岁时：分别为平均0.61和平均0.72，p = 0.21；11岁时：分别为平均0.96和平均1.21，p = 0.07）。此外，在校正年龄和性别后，自身抗体阳性与较低的HOMA-IR值相关（p = 0.01）。在2岁（分别为平均0.07和平均0.16）、5岁（分别为平均0.06和0.08）、8岁（分别为平均 - 0.09和平均0.02）和11岁（分别为平均0.22和平均0.16）时，胰岛自身抗体阳性和阴性儿童的BMI-SDS相似，且与国家参考值相似。
结论/解读：BABYDIAB队列中胰岛自身抗体阳性儿童不存在胰岛素抵抗，在胰岛自身抗体血清转化前后及早期BMI也没有升高。这些发现与胰岛素抵抗是胰岛自身免疫危险因素的观点不一致。
