Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 East 17th Ave, Aurora, CO 80045, USA.
Diabetologia. 2012 Dec;55(12):3359-68. doi: 10.1007/s00125-012-2719-6. Epub 2012 Sep 20.
AIMS/HYPOTHESIS: Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study.
Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models.
Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month).
CONCLUSIONS/INTERPRETATION: SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.
目的/假设：很少有研究探讨过青少年糖尿病患者β细胞丢失的流行病学。本报告描述了 SEARCH for Diabetes in Youth 研究中，通过空腹 C 肽 (FCP) 评估的β细胞功能的演变和主要决定因素。
参与者为 1277 名患有糖尿病的青少年（948 名糖尿病自身抗体 [DAs] 阳性，329 名 DAs 阴性），诊断时年龄<20 岁，自诊断后中位数随访 8 个月，约 30 个月。我们使用重复测量一般线性模型，对 log FCP 变化率与感兴趣的决定因素之间的关系进行建模。
在 DA 阳性的青少年中，β细胞功能每月下降 4%，与人口统计学因素（年龄、性别、种族/民族）、自身免疫遗传易感性（HLA 风险）、HbA1c 和 BMI z 评分或胰岛素抵抗无关。在 DA 阴性的青少年中，β细胞丢失存在明显的异质性，反映了病因学上混杂的一组。这一组可能包括未检测到自身免疫的青少年（其下降与 DA 阳性青少年相似）和非自身免疫、胰岛素抵抗性糖尿病的青少年，其下降幅度有限（每月约 0.7%）。
结论/解释：SEARCH 为大量患有糖尿病的青少年提供了β细胞功能下降的独特估计，表明自身免疫是主要原因。这些数据有助于更好地了解青少年糖尿病β细胞功能的临床演变，为糖尿病的病因分类提供了强有力的支持，并可能为针对高危人群的三级预防措施提供信息。
