Four biomarkers are commonly employed to diagnose B12 deficiency: vitamin B12 (B12), holotranscobalamin (HoloTC), methylmalonic acid (MMA), and homocysteine (Hcy). 4cB12, a combined index of the B12 status, has been suggested to improve the recognition of B12 deficiency. We aimed to evaluate the four different markers for detecting B12 deficiency, as determined by 4cB12. Within a large, mixed patient population, 11,833 samples had concurrent measurements of B12, HoloTC, MMA, and Hcy. 4cB12 was calculated according to the methods described by Fedosov. Diagnostic cutoffs as well as diagnostic accuracy for the detection of B12 deficiency were assessed with receiver operating characteristic (ROC) analysis. The median age was 56 years, and women accounted for 58.8% of the samples. Overall, the area under the curve (AUC) for the detection of subclinical B12 deficiency was highest for HoloTC (0.92), followed by MMA (0.91), B12 (0.9) and Hcy (0.78). The difference between HoloTC and B12 was driven by a significantly higher AUC for HoloTC (0.93) than for B12 (0.89), MMA (0.91), and Hcy in women 50 years and older (0.79; for all). In the detection of subclinical B12 deficiency, there were no significant differences in the AUCs of HoloTC, B12, and MMA among men and women <50 years. In conclusion, in years and in men, HoloTC, MMA, or Hcy do not appear superior to B12 for the detection of B12 deficiency. For women 50 years and older, HoloTC seems to be the preferred first-line marker for the detection of subclinical B12 deficiency.

中文翻译：

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全反钴胺素，维生素B12，甲基丙二酸和同型半胱氨酸在大量混合患者群体中检测B12缺乏症的诊断准确性。

通常使用四种生物标记物来诊断B12缺乏症：维生素B12（B12），全反钴胺素（HoloTC），甲基丙二酸（MMA）和高半胱氨酸（Hcy）。已建议使用4cB12（B12状态的综合指标）来提高对B12缺乏症的认识。我们旨在评估由4cB12确定的用于检测B12缺乏症的四种不同标记。在大量的混合患者人群中，有11,833个样本同时测量了B12，HoloTC，MMA和Hcy。根据Fedosov描述的方法计算4cB12。使用接收器工作特征（ROC）分析评估了诊断B12缺乏症的临界值和诊断准确性。中位年龄为56岁，女性占样本的58.8％。总体，用于检测亚临床B12缺乏症的曲线下面积（AUC）最高的是HoloTC（0.92），其次是MMA（0.91），B12（0.9）和Hcy（0.78）。HoloTC和B12之间的差异是由HoloTC（0.93）的AUC显着高于B12（0.89），MMA（0.91）和Hcy的50岁及以上女性（0.79;对所有人）。在亚临床B12缺乏症的检测中，<50岁的男性和女性的HoloTC，B12和MMA的AUC没有显着差异。总之，在在男性中，HoloTC，MMA或Hcy在检测B12缺乏症方面似乎并不优于B12。对于50岁以上的女性，HoloTC似乎是检测亚临床B12缺乏症的首选一线标记。