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The Capital Region of Denmark - a part of Copenhagen University Hospital
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High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus

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  • Anette P 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
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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 of β-cell dysfunction.

Objectives: We aimed to estimate the prevalence of possibly pathogenic variants in the maturity-onset diabetes of the young genes GCK, HNF1A, HNF4A, HNF1B, and INS among 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 of GCK, HNF1A, HNF4A, HNF1B, and INS 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.

Main Outcome Measures: The prevalence of possibly pathogenic variants in GCK, HNF1A, HNF4A, HNF1B, and INS was 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 combined GCK, HNF1A, HNF4A, HNF1B, and INS 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 GCK, HNF1A, HNF4A, HNF1B, or INS.

Conclusions: Almost 6% of Danish women with diet-treated GDM have possibly pathogenic variants in GCK, HNF1A, HNF4A, HNF1B, or INS. These women are at high risk of developing diabetes after pregnancy. Thus screening for variants in GCK, HNF1A, HNF4A, HNF1B, and INS should be considered among women with GDM.

Original languageEnglish
JournalJournal of the Endocrine Society
Volume1
Issue number6
Pages (from-to)681-690
Number of pages10
ISSN2472-1972
DOIs
Publication statusPublished - 1 Jun 2017

ID: 52343541