Management and pregnancy outcomes of women with GCK-MODY enrolled in the US Monogenic Diabetes Registry
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GCK-MODY is characterized by mild hyperglycemia. Treatment is not required outside of pregnancy. During pregnancy, insulin treatment is recommended if second trimester fetal ultrasound monitoring shows macrosomia, suggesting the fetus has not inherited the GCK gene. There are limited data about GCK-MODY management in pregnancy. The aim of this study was to examine clinical management and pregnancy outcomes amongst women with a known diagnosis of GCK-MODY.
In this observational, cross-sectional study, a survey was distributed via Redcap to women ≥ 18 years enrolled in the University of Chicago Monogenic Diabetes Registry (n = 94). All or part of the survey was completed by 54 women (128 pregnancies).
There were 78 term births (61%), 15 pre-term births (12%), and 24 miscarriages (19%). Of the 39 pregnancies where insulin was given, 22 (56%) had occasional or frequent hypoglycemia including 9 with severe hypoglycemia. Average birth weight for full-term GCK-affected infants was significantly less in cases of maternal insulin treatment versus no treatment (2967 and 3725 g, p = 0.005). For GCK-unaffected infants, conclusions are limited by small sample size but large for gestational age (LGA) was common with maternal insulin treatment (56%) and no treatment (33%), p = 0.590.
The observed miscarriage rate was comparable to the background US population rate (15–20%). Patients treated with insulin experienced a 23% incidence of severe hypoglycemia and lower birth weights were observed in the insulin-treated, GCK-affected neonates. These data support published guidelines of no treatment if the fetus is suspected to have inherited GCK-MODY and highlight the importance of additional studies to determine optimal pregnancy management for GCK-MODY, particularly among unaffected fetuses.
KeywordsGlucokinase MODY Pregnancy
L.T.D. developed the study concept and design, acquired data, analyzed and interpreted data, drafted the manuscript, and critically revised the manuscript for important intellectual content. L.R.L. acquired data, critically revised the manuscript for important intellectual content, and provided administrative, technical, or material support. M. S. analyzed and interpreted data, and critically revised the manuscript for important intellectual content. S.A.W.G. developed the study concept and design and critically revised the manuscript for important intellectual content. L.H.P. developed the study concept and design, critically revised the manuscript for important intellectual content, and obtained funding. R.N.N. developed the study concept and design, acquired data, analyzed and interpreted data, drafted the manuscript, critically revised the manuscript for important intellectual content, obtained funding, and supervised the study. L.T.D. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This work has been presented in poster form at the Endocrine Society Meeting (Chicago, IL, 3/19/18) and ADA Scientific Sessions (Orlando, FL, 6/24/18). This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [grant numbers T32 DK007011, R01 DK104942, P30 DK020595, K23 DK114564] and the CTSA [grant number UL1 TR002389]. We thank Kristen Wroblewski, MS for assistance with statistical analysis.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
This study was approved by the University of Chicago Institutional Review Board and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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