Gjesing Anette P, Rui Gao, Lauenborg Jeannet, Have Christian Theil, Hollensted Mette, Andersson Ehm, Grarup Niels, Sun Jihua, Quan Shi, Brandslund Ivan, Damm Peter, Pedersen Oluf, Wang Jun, Hansen Torben
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
BGI-Shenzhen, Shenzhen, 518083 China.
J Endocr Soc. 2017 Apr 27;1(6):681-690. doi: 10.1210/js.2017-00040. eCollection 2017 Jun 1.
Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with first recognition during pregnancy, is a heterogeneous form of diabetes characterized by various degrees of -cell dysfunction.
We aimed to estimate the prevalence of possibly pathogenic variants in the maturity-onset diabetes of the young genes , , , , and among women with GDM. Furthermore, we examined the glucose tolerance status in variant carriers vs noncarriers at follow-up.
We sequenced the coding regions and intron/exon boundaries of , , , , and using targeted region capture and next-generation sequencing in 354 Danish women with diet-treated GDM. Glucose tolerance was examined at follow-up 10 years after the index pregnancy.
The prevalence of possibly pathogenic variants in , , , , and was estimated, and differences in anthropometric traits, high-sensitivity C-Reactive Protein (CRP), and glucose metabolism were measured.
At baseline, 17 possibly disease-causing variants were found in 21 women, revealing a combined , , , , and variant prevalence of 5.9% (95% confidence interval: 3.5% to 8.4%). At follow-up, 15 out of 135 women with diabetes (11%) were carriers of variants in , , , , or .
Almost 6% of Danish women with diet-treated GDM have possibly pathogenic variants in , , , , or . These women are at high risk of developing diabetes after pregnancy. Thus screening for variants in , , , , and should be considered among women with GDM.
妊娠期糖尿病（GDM）定义为孕期首次发现的任何程度的葡萄糖不耐受，是一种以不同程度的β细胞功能障碍为特征的异质性糖尿病形式。
我们旨在估计年轻型糖尿病相关基因（MODY）1、2、3、4和5中可能的致病变异在妊娠期糖尿病女性中的患病率。此外，我们在随访中检查了变异携带者与非携带者的糖耐量状态。
设计、地点和患者：我们对354名接受饮食治疗的丹麦妊娠期糖尿病女性，使用靶向区域捕获和下一代测序技术对MODY1、2、3、4和5的编码区及内含子/外显子边界进行测序。在本次妊娠10年后的随访中检查糖耐量。
估计MODY1、2、3、4和5中可能的致病变异的患病率，并测量人体测量学特征、高敏C反应蛋白（CRP）和葡萄糖代谢的差异。
在基线时，21名女性中发现了17个可能致病的变异，显示MODY1、2、3、4和5变异的合并患病率为5.9%（95%置信区间：3.5%至8.4%）。在随访中，135名糖尿病女性中有15名（11%）是MODY1、2、3、4或5变异的携带者。
近6%接受饮食治疗的丹麦妊娠期糖尿病女性在MODY1、2、3、4或5中有可能的致病变异。这些女性在妊娠后患糖尿病的风险很高。因此，对于妊娠期糖尿病女性应考虑筛查MODY1、2、3、4和5中的变异。
