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

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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Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of the Endocrine Society
Vol/bind1
Udgave nummer6
Sider (fra-til)681-690
ISSN2472-1972
DOI
StatusUdgivet - 2017

Fingeraftryk

Gestational Diabetes
Type 2 Diabetes Mellitus
Diet
Glucose Intolerance
Introns
Outcome Assessment (Health Care)
Confidence Intervals

Citer dette

Gjesing, A. P., Rui, G., Lauenborg, J., Have, C. T., Hollensted, M., Andersson, E., ... Hansen, T. (2017). High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus. Journal of the Endocrine Society, 1(6), 681-690. https://doi.org/10.1210/js.2017-00040
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. / High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus. I: Journal of the Endocrine Society. 2017 ; Bind 1, Nr. 6. s. 681-690.
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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.",
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author = "Gjesing, {Anette P} 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",
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Gjesing, AP, 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', Journal of the Endocrine Society, bind 1, nr. 6, s. 681-690. https://doi.org/10.1210/js.2017-00040

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

I: Journal of the Endocrine Society, Bind 1, Nr. 6, 2017, s. 681-690.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

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

AU - Gjesing, Anette P

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

Y1 - 2017

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 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.

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 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.

KW - Journal Article

U2 - 10.1210/js.2017-00040

DO - 10.1210/js.2017-00040

M3 - Journal article

VL - 1

SP - 681

EP - 690

JO - Journal of the Endocrine Society

JF - Journal of the Endocrine Society

SN - 2472-1972

IS - 6

ER -