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

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

doi:10.1210/js.2017-00040

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

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

Department of Clinical Medicine

19 Citations (Scopus)

110 Downloads (Pure)

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 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.

Original language	English
Journal	Endocrine Research
Volume	1
Issue number	6
Pages (from-to)	681-690
Number of pages	10
ISSN	2472-1972
DOIs	https://doi.org/10.1210/js.2017-00040
Publication status	Published - Jun 2017

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Gjesing, A. M. P., Rui, G., Lauenborg, J., Have, C. T., Hollensted, M., Andersson, E., Grarup, N., Sun, J., Quan, S., Brandslund, I., Damm, P., Pedersen, O., Wang, J., & Hansen, T. (2017). High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus. Endocrine Research, 1(6), 681-690. https://doi.org/10.1210/js.2017-00040

Gjesing, AMP, Rui, G, Lauenborg, J, Have, CT, Hollensted, M, Andersson, E, Grarup, N, Sun, J, Quan, S, Brandslund, I, Damm, P , Pedersen, O, Wang, J & Hansen, T 2017, 'High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus', Endocrine Research, vol. 1, no. 6, pp. 681-690. https://doi.org/10.1210/js.2017-00040

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title = "High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus",

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 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.",

author = "Gjesing, {Anette Marianne Prior} and Gao Rui and Jeannet Lauenborg and Have, {Christian Theil} and Mette Hollensted and Ehm Andersson and Niels Grarup and Jihua Sun and Shi Quan and Ivan Brandslund and Peter Damm and Oluf Pedersen and Jun Wang and Torben Hansen",

year = "2017",

month = jun,

doi = "10.1210/js.2017-00040",

language = "English",

volume = "1",

pages = "681--690",

journal = "Endocrine Research Communications",

issn = "0743-5800",

publisher = "Taylor & Francis",

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TY - JOUR

T1 - High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus

AU - Gjesing, Anette Marianne Prior

AU - Rui, Gao

AU - Lauenborg, Jeannet

AU - Have, Christian Theil

AU - Hollensted, Mette

AU - Andersson, Ehm

AU - Grarup, Niels

AU - Sun, Jihua

AU - Quan, Shi

AU - Brandslund, Ivan

AU - Damm, Peter

AU - Pedersen, Oluf

AU - Wang, Jun

AU - Hansen, Torben

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

U2 - 10.1210/js.2017-00040

DO - 10.1210/js.2017-00040

M3 - Journal article

C2 - 29264522

SN - 0743-5800

VL - 1

SP - 681

EP - 690

JO - Endocrine Research Communications

JF - Endocrine Research Communications

IS - 6

ER -

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

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