High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus
Research output: Contribution to journal › Journal article › Research › peer-review
- High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus
Final published version, 168 KB, PDF document
168 KB, PDF document
Anette Marianne Prior Gjesing, Gao Rui, Jeannet Lauenborg, Christian Theil Have, Mette Hollensted, Ehm Andersson, Niels Grarup, Jihua Sun, Shi Quan, Ivan Brandslund, Peter Damm, Oluf Pedersen, Jun Wang, Torben Hansen
Context: 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 ofβ-cell dysfunction.
Objectives: We aimed to estimate the prevalence of possibly pathogenic variants in the maturity-onset diabetes of the young genesGCK,HNF1A,HNF4A,HNF1B, andINSamong women with GDM. Furthermore, we examined the glucose tolerance status in variant carriers vs noncarriers at follow-up.
Design Setting and Patients: We sequenced the coding regions and intron/exon boundaries ofGCK,HNF1A,HNF4A,HNF1B, andINSusing 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.
Main Outcome Measures: The prevalence of possibly pathogenic variants inGCK,HNF1A,HNF4A,HNF1B, andINSwas estimated, and differences in anthropometric traits, high-sensitivity C-Reactive Protein (CRP), and glucose metabolism were measured.
Results: At baseline, 17 possibly disease-causing variants were found in 21 women, revealing a combinedGCK,HNF1A,HNF4A,HNF1B, andINSvariant 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 inGCK,HNF1A,HNF4A,HNF1B, orINS.
Conclusions: Almost 6% of Danish women with diet-treated GDM have possibly pathogenic variants inGCK,HNF1A,HNF4A,HNF1B, orINS. These women are at high risk of developing diabetes after pregnancy. Thus screening for variants inGCK,HNF1A,HNF4A,HNF1B, andINSshould be considered among women with GDM.
|Number of pages||10|
|Publication status||Published - 2017|
Number of downloads are based on statistics from Google Scholar and www.ku.dk