Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
Department of Experimental Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
Front Endocrinol (Lausanne). 2020 May 20;11:268. doi: 10.3389/fendo.2020.00268. eCollection 2020.
The prevalence among pregnant women with diabetes of monogenic diabetes due to glucokinase deficit (GCK-MODY) varies from 0 to 80% in different studies, based on the chosen selection criteria for genetic test. New pregnancy-specific Screening Criteria (NSC), validated on an Anglo-Celtic pregnant cohort, have been proposed and include pre-pregnancy BMI <25 kg/m and fasting glycemia >99 mg/dl. Our aim was to estimate the prevalence of GCK-MODY and to evaluate the diagnostic performance of NSC in our population of women with diabetes in pregnancy. We retrospectively selected from our database of 468 diabetic pregnant patients in Sant'Andrea Hospital, in Rome, from 2010 to 2018, all the women who received a genetic test for GCK deficit because of specific clinical features. We estimated the prevalence of GCK-MODY among tested women and the minimum prevalence in our entire population with non-autoimmune diabetes. We evaluated diagnostic performance of NSC on the tested cohort and estimated the eligibility to genetic test based on NSC in the entire population. A total of 409 patients had diabetes in pregnancy, excluding those with autoimmune diabetes; 21 patients have been tested for GCK-MODY, 8 have been positive and 13 have been negative (2 of them had HNF1-alfa mutations and 1 had HNF4-alfa mutation). We found no significant differences in clinical features between positive and negative groups except for fasting glycemia, which was higher in the positive group. The minimum prevalence of monogenic diabetes in our population was 2.4%. The minimum prevalence of GCK-MODY was 1.95%. In the tested cohort, the prevalence of GCK-MODY was 38%. In this group, NSC sensitivity is 87% and specificity is 30%, positive predictive value is 43%, and negative predictive value is 80%. Applying NSC on the entire population of women with non-autoimmune diabetes in pregnancy, 41 patients (10%) would be eligible for genetic test; considering a fasting glycemia >92 mg/dl, 85 patients (20.7%) would be eligible. In our population, NSC have good sensitivity but low specificity, probably because there are many GDM with GCK-MODY like features. It is mandatory to define selective criteria with a good diagnostic performance on Italian population, to avoid unnecessary genetic tests.
基于用于基因检测的选择标准不同，患有因葡萄糖激酶缺陷导致的单基因糖尿病（GCK-MODY）的孕妇在不同研究中的患病率从 0 到 80%不等。新的妊娠特异性筛查标准（NSC）已在一个英裔凯尔特裔妊娠队列中得到验证，其纳入标准为孕前 BMI<25kg/m2 和空腹血糖>99mg/dl。我们的目的是评估 GCK-MODY 在我们妊娠糖尿病患者中的患病率，并评估 NSC 的诊断性能。我们从 2010 年至 2018 年在罗马 Sant'Andrea 医院的 468 名糖尿病孕妇的数据库中回顾性选择了所有因特殊临床特征而接受 GCK 缺陷基因检测的女性。我们估计了在接受检测的女性中 GCK-MODY 的患病率，以及整个非自身免疫性糖尿病人群中的最低患病率。我们在检测队列中评估了 NSC 的诊断性能，并根据 NSC 估计了整个人群中进行基因检测的资格。共有 409 名患者患有妊娠糖尿病，不包括自身免疫性糖尿病患者；21 名患者接受了 GCK-MODY 检测，其中 8 例阳性，13 例阴性（其中 2 例为 HNF1-ALFA 突变，1 例为 HNF4-ALFA 突变）。除了空腹血糖，阳性组更高之外，两组之间在临床特征方面没有显著差异。我们人群中单基因糖尿病的最低患病率为 2.4%。GCK-MODY 的最低患病率为 1.95%。在检测队列中，GCK-MODY 的患病率为 38%。在该组中，NSC 的敏感性为 87%，特异性为 30%，阳性预测值为 43%，阴性预测值为 80%。将 NSC 应用于整个非自身免疫性妊娠糖尿病患者人群中，将有 41 名（10%）患者符合基因检测条件；如果将空腹血糖>92mg/dl 纳入考虑范围，将有 85 名（20.7%）患者符合条件。在我们的人群中，NSC 具有良好的敏感性，但特异性较低，这可能是因为有许多 GDM 具有 GCK-MODY 样特征。有必要在意大利人群中定义具有良好诊断性能的选择性标准，以避免不必要的基因检测。
