Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, München-Neuherberg, Germany.
Biotechnol Adv. 2020 Mar-Apr;39:107359. doi: 10.1016/j.biotechadv.2019.02.015. Epub 2019 Feb 23.
Harmonization of biomarkers is important for the comparability of laboratory results as it allows the definition of universal reference values and clinical decision limits. In diabetology, immunoassays are widely used to determine HbA1c, C-peptide, insulin, and autoantibodies to beta cell proteins, which are essential biomarkers for the diagnosis and classification of diabetes mellitus. Furthermore, as large clinical studies have identified HbA1c as a predictor for the development of diabetic complications, HbA1c has evolved as the general treatment target. For decades, the use of non-harmonized assays caused confusion. After the standardization of HbA1c, the worldwide comparability improved and increased the confidence in this laboratory biomarker. Insulin and C-peptide are not only valuable biomarkers to assess beta-cell function, but may also be used to evaluate insulin resistance, a metabolic feature of type 2 diabetes often occurring before its manifestation. Long-lasting efforts led to substantial improvements in the harmonization process of C-peptide assays, but harmonization of insulin assays is still ongoing. Therefore, C-peptide is now sometimes used as a surrogate biomarker for insulin. Furthermore, autoantibodies against beta cell components are important biomarkers for the accurate differentiation of type 1, type 2, and other special types of diabetes. Owing to the heterogeneity of these autoantibodies against beta cell proteins, harmonization is very difficult to achieve. International efforts are in progress to harmonize the current assays, as the presence of autoantibodies against beta cell proteins predicts the development of type 1 diabetes in early life. In conclusion, clinical studies linking diagnosis, classification, prediction, and treatment to laboratory values of the respective biomarkers need to be harmonized to avoid misdiagnosis and incorrect clinical decisions, thus improving patient care and safety.
生物标志物的协调一致对于实验室结果的可比性非常重要，因为它允许定义通用参考值和临床决策界限。在糖尿病学中，免疫测定被广泛用于确定 HbA1c、C 肽、胰岛素和胰岛自身抗体，这些都是糖尿病诊断和分类的重要生物标志物。此外，由于大型临床研究已经确定 HbA1c 是糖尿病并发症发展的预测指标，因此 HbA1c 已成为一般治疗目标。几十年来，非协调免疫测定的使用造成了混乱。在 HbA1c 标准化之后，全球可比性得到了提高，对这种实验室生物标志物的信心也增强了。胰岛素和 C 肽不仅是评估胰岛功能的有价值的生物标志物，还可用于评估胰岛素抵抗，这是 2 型糖尿病的代谢特征，常发生在其表现之前。经过长期努力，C 肽测定的协调一致过程取得了实质性的改进，但胰岛素测定的协调一致仍在进行中。因此，C 肽现在有时被用作胰岛素的替代生物标志物。此外，针对胰岛β细胞成分的自身抗体是准确区分 1 型、2 型和其他特殊类型糖尿病的重要生物标志物。由于针对胰岛β细胞蛋白的这些自身抗体存在异质性，因此很难实现协调一致。正在进行国际努力以协调当前的测定方法，因为针对胰岛β细胞蛋白的自身抗体的存在可预测 1 型糖尿病在生命早期的发展。总之，需要协调将与诊断、分类、预测和治疗相关的临床研究与各自生物标志物的实验室值联系起来，以避免误诊和错误的临床决策，从而改善患者的护理和安全。
