OBJECTIVE Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes. In 2009, >80% of U.K. cases were estimated to be misdiagnosed. Since then, there have been a number of initiatives to improve the awareness and detection of MODY, including education initiatives (Genetic Diabetes Nurse [GDN] project), the MODY probability calculator, and targeted next-generation sequencing (tNGS). We examined how the estimated prevalence of MODY and other forms of monogenic diabetes diagnosed outside the neonatal period has changed over time and how the initiatives have impacted case finding. RESEARCH DESIGN AND METHODS U.K. referrals for genetic testing for monogenic diabetes diagnosed >1 year of age from 1 January 1996 to 31 December 2019 were examined. Positive test rates were compared for referrals reporting GDN involvement/MODY calculator use with those that did not. RESULTS A diagnosis of monogenic diabetes was confirmed in 3,860 individuals, more than threefold higher than 2009 (1 January 1996 to 28 February 2009, n = 1,177). Median age at diagnosis in probands was 21 years. GDN involvement was reported in 21% of referrals; these referrals had a higher positive test rate than those without GDN involvement (32% vs. 23%, P < 0.001). MODY calculator usage was indicated in 74% of eligible referrals since 2014; these referrals had a higher positive test rate than those not using the calculator (33% vs. 25%, P = 0.001). Four hundred ten (10.6%) cases were identified through tNGS. Monogenic diabetes prevalence was estimated to be 248 cases/million (double that estimated in 2009 because of increased case finding). CONCLUSIONS Since 2009, referral rates and case diagnosis have increased threefold. This is likely to be the consequence of tNGS, GDN education, and use of the MODY calculator.

中文翻译：

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认识和测试的提高导致英国单基因糖尿病的鉴定在过去 10 年中增加了三倍

目的 青少年成年发病型糖尿病 (MODY) 是一种罕见的单基因糖尿病。2009 年，估计有超过 80% 的英国病例被误诊。从那时起，已经有许多举措来提高对 MODY 的认识和检测，包括教育举措（遗传糖尿病护士 [GDN] 项目）、MODY 概率计算器和靶向下一代测序（tNGS）。我们研究了在新生儿期以外诊断出的 MODY 和其他形式的单基因糖尿病的估计患病率如何随时间变化，以及这些举措如何影响病例发现。研究设 将报告 GDN 参与/MODY 计算器使用情况的推荐人与未使用的推荐人的阳性测试率进行了比较。结果 3,860 人确诊为单基因糖尿病，比 2009 年高出三倍多（1996 年 1 月 1 日至 2009 年 2 月 28 日，n = 1,177）。先证者诊断时的中位年龄为 21 岁。21% 的转介报告涉及 GDN；这些转诊的阳性检测率高于未参与 GDN 的患者（32% 对 23%，P < 0.001）。自 2014 年以来，74% 的合格推荐人使用了 MODY 计算器；这些推荐人的阳性检测率高于不使用计算器的人（33% vs. 25%，P = 0.001）。通过 tNGS 发现了 410 例 (10.6%) 病例。单基因糖尿病患病率估计为 248 例/百万（由于发现病例增加，是 2009 年估计的两倍）。结论 自 2009 年以来，转诊率和病例诊断增加了三倍。这很可能是 tNGS、GDN 教育和使用 MODY 计算器的结果。