Guy's and St Thomas' NHS Foundation Trust London UK.
Royal Devon and Exeter Hospital Exeter UK.
J Diabetes Investig. 2016 May;7(3):332-7. doi: 10.1111/jdi.12432. Epub 2015 Oct 26.
AIMS/INTRODUCTION: Monogenic diabetes accounts for approximately 1-2% of all diabetes, and is difficult to distinguish from type 1 and type 2 diabetes. Molecular diagnosis is important, as the molecular subtype directs appropriate treatment. Patients are selected for testing according to clinical criteria, but up to 80% of monogenic diabetes in the UK has not been correctly diagnosed. We investigated outcomes of genetic testing in our center to compare methods of selecting patients, and consider avenues to increase diagnostic efficiency.
We reviewed 36 probands tested for monogenic diabetes in the last 10 years in a large adult diabetes outpatient clinic, serving an ethnically diverse urban population. We compared published clinical criteria and an online maturity onset diabetes of the young calculator applied to these 36 patients, and presented the predictions together with the molecular results.
The overall mutation detection rate was 42%, reflecting the strict clinical selection process applied before genetic testing. Both methods had high sensitivity for identifying patients with mutations: 88 and 89% for the clinical criteria and online calculator, respectively. Cascade testing in a total of 16 relatives led to diagnosis of a further 13 cases.
Existing patient selection criteria were effective in identifying patients with monogenic forms of diabetes, but the number of patients missed using these strict criteria is unknown. Because of the potential savings resulting from correct molecular diagnosis, it is possible that testing a larger pool of patients using less stringent selection criteria would be cost-effective. Further evidence is required to inform this assessment.
目的/引言：单基因糖尿病占所有糖尿病的 1-2%左右，难以与 1 型和 2 型糖尿病区分。分子诊断很重要，因为分子亚型指导着合适的治疗方法。根据临床标准选择患者进行检测，但英国高达 80%的单基因糖尿病尚未得到正确诊断。我们调查了我们中心的基因检测结果，以比较选择患者的方法，并考虑提高诊断效率的途径。
我们回顾了过去 10 年在一家大型成人糖尿病门诊诊所中对 36 名单基因糖尿病患者进行的检测，该诊所服务于一个种族多样化的城市人群。我们比较了已发表的临床标准和应用于这 36 名患者的在线青年发病成年型糖尿病计算器，并将预测结果与分子结果一起呈现。
总的基因突变检测率为 42%，反映了在进行基因检测之前应用的严格临床选择过程。两种方法在识别携带突变的患者方面均具有高敏感性：临床标准和在线计算器分别为 88%和 89%。对总共 16 名亲属进行级联检测，又诊断出了 13 例。
现有的患者选择标准在识别单基因糖尿病患者方面是有效的，但使用这些严格标准遗漏的患者数量尚不清楚。由于正确的分子诊断可以节省成本，因此使用不太严格的选择标准对更大的患者群体进行测试可能具有成本效益。需要进一步的证据来支持这一评估。
