Datz N, Nestoris C, von Schütz W, Danne T, Driesel A J, Maringa M, Kordonouri O
Diabeteszentrum für Kinder und Jugendliche, Kinderkrankenhaus auf der Bult, Hannover, Deutschland.
Dtsch Med Wochenschr. 2011 May;136(21):1111-5. doi: 10.1055/s-0031-1280519. Epub 2011 May 17.
Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening.
Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria.
Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment.
In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment.
由于临床表现多样且糖尿病专家对这类糖尿病的经验有限，单基因糖尿病常被偶然诊断出来。本研究的目的是评估用于有效筛查的临床参数。
临床参数包括：糖尿病发病时糖尿病特异性抗体阴性、糖尿病家族史阳性以及糖尿病治疗一年后胰岛素需求量低至中等。通过对肝细胞核因子4α（MODY 1）、葡萄糖激酶（MODY 2）和肝细胞核因子1α/转录因子1（MODY 3）的编码区进行测序进行分子检测，在一名患者中对肝细胞核因子1β/转录因子2区域（MODY 5）进行了检测。292例接受胰岛素治疗的患者中，39例谷氨酸脱羧酶抗体（GADA）和胰岛细胞抗原2抗体（IA2A）呈阴性，8例（20.5%）患者符合其他两项标准。
在5例（63%）患者中发现分子检测结果呈阳性（2例为MODY 2，2例为MODY 3，1例为MODY 5）。MODY患者发病时的平均年龄为10.6±5.3岁（范围2.6 - 15岁），糖化血红蛋白（HbA1c）为8.4±3.1%（6.5 - 13.9%），直至诊断为MODY的平均糖尿病病程为3.3±3.6年（0.8 - 9.6年），胰岛素需求量为0.44±0.17 U/kg/d（0.2 - 0.6 U/kg/d）。MODY 3患者从胰岛素治疗改为瑞格列奈治疗，MODY 2患者被建议停止胰岛素治疗。
对于糖尿病发病时糖尿病特异性抗体阴性、有阳性家族史且胰岛素需求量低至中等的患者，建议进行MODY的基因筛查。密切关注这些临床参数可能会促使早期进行基因检测并采取适当的治疗。
