Format

Send to

Choose Destination
J Endocr Soc. 2017 Apr 27;1(6):681-690. doi: 10.1210/js.2017-00040. eCollection 2017 Jun 1.

High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus.

Author information

1
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.
2
BGI-Shenzhen, Shenzhen, 518083 China.
3
Department of Gynecology and Obstetrics, Copenhagen University Hospital, 2730 Herlev, Denmark.
4
Department of Clinical Biochemistry, Vejle Hospital, DK-7100 Vejle, Denmark.
5
Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.
6
Center for Pregnant Women With Diabetes, Department of Obstetrics, Rigshospitalet, 2100 Copenhagen, Denmark.
7
Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

Abstract

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.

KEYWORDS:

MODY; genes; genetic screening; gestational diabetes; monogenic diabetes

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center