Department of Pediatrics, College of Medicine, University of South Florida, Tampa, Florida, USA.
Diabetes Care. 2012 Oct;35(10):1975-80. doi: 10.2337/dc12-0183. Epub 2012 Jul 11.
To establish and compare the prognostic accuracy of immunologic and metabolic markers in predicting onset of type 1 diabetes in those with high risk in a prospective study.
A total of 339 subjects from the Diabetes Prevention Trial-Type 1 (DPT-1) parenteral study, who were islet cell antibody (ICA)-positive, with low first-phase insulin response (FPIR) and/or abnormal glucose tolerance at baseline, were followed until clinical diabetes onset or study end (5-year follow-up). The prognostic performance of biomarkers was estimated using receiver operating characteristic (ROC) curve analysis and compared with nonparametric testing of ROC curve areas. Pearson correlation was used to assess the relationship between the markers.
Individually, insulin autoantibody titer, ICA512A titer, peak C-peptide, 2-h glucose, FPIR, and FPIR/homeostasis model assessment of insulin resistance provided modest but significant prognostic values for 5-year risk with a similar level of area under ROC curve ranging between 0.61 and 0.67. The combination of 2-h glucose, peak C-peptide, and area under the curve C-peptide significantly improved the prognostic accuracy compared with any solitary index (P < 0.05) with an area under ROC curve of 0.76 (95% CI 0.70-0.81). The addition of antibody titers and/or intravenous glucose tolerance test (IVGTT) markers did not increase the prognostic accuracy further (P = 0.46 and P = 0.66, respectively).
The combination of metabolic markers derived from the oral glucose tolerance test improved accuracy in predicting progression to type 1 diabetes in a population with ICA positivity and abnormal metabolism. The results indicate that the autoimmune activity may not alter the risk of type 1 diabetes after metabolic function has deteriorated. Future intervention trials may consider eliminating IVGTT measurements as an effective cost-reduction strategy for prognostic purposes.
在一项前瞻性研究中，建立并比较免疫和代谢标志物在预测高危人群 1 型糖尿病发病中的预后准确性。
共有 339 名来自糖尿病预防试验-1（DPT-1）的受试者参与了本项研究，这些受试者均为胰岛细胞抗体（ICA）阳性，在基线时存在低胰岛素第一时相反应（FPIR）和/或葡萄糖耐量异常。这些受试者一直随访至临床糖尿病发病或研究结束（5 年随访）。使用受试者工作特征（ROC）曲线分析来评估生物标志物的预后性能，并与 ROC 曲线下面积的非参数检验进行比较。使用 Pearson 相关性分析来评估标志物之间的关系。
单独来看，胰岛素自身抗体滴度、ICA512A 滴度、峰值 C 肽、2 小时血糖、FPIR 和 FPIR/稳态模型评估的胰岛素抵抗提供了对 5 年风险的适度但显著的预后价值，ROC 曲线下面积的相似水平在 0.61 到 0.67 之间。与任何单一指标相比，2 小时血糖、峰值 C 肽和 C 肽曲线下面积的组合显著提高了预测准确性（P < 0.05），ROC 曲线下面积为 0.76（95%CI 0.70-0.81）。增加抗体滴度和/或静脉葡萄糖耐量试验（IVGTT）标志物并不能进一步提高预测准确性（P = 0.46 和 P = 0.66）。
来自口服葡萄糖耐量试验的代谢标志物的组合改善了 ICA 阳性和代谢异常人群预测 1 型糖尿病进展的准确性。结果表明，在代谢功能恶化后，自身免疫活动可能不会改变 1 型糖尿病的发病风险。未来的干预试验可能考虑消除 IVGTT 测量，作为一种用于预后目的的有效降低成本的策略。
