Glucose variability in pregnant women with newly diagnosed hyperglycemia

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Abstract

Background: High-performance parallel next-generation sequencing (NGS) allows for identification of various maturity-onset diabetes of the young (MODY) subtypes also during pregnancy. As this method is expensive and time-consuming, it has proposed to use various predictors for the diagnosis of mutation in the hexokinase (GCK)/MODY2 gene, helping to select the patients for subsequent molecular genetic testing. Hyperglycemia due to MODY2 is commonly newly diagnosed during pregnancy; therefore, there is a search for factors specific to this mutation in pregnant women.

Aim: To evaluate blood glucose variability in pregnant women with newly diagnosed hyperglycemia at early gestation and to determine the threshold value of the glycemic variability coefficient for pregnant women with a mutation in the GCK/MODY2 gene.

Materials and methods: This observational single center study included 41  pregnant women with newly diagnosed early hyperglycemia (not meeting the criteria for manifest diabetes mellitus). Molecular genetic testing was performed in all of them. According to its results, they were retrospectively categorized into two groups: with early gestational diabetes mellitus (GDM, no mutations) and with hyperglycemia related to a mutation in the GCK/MODY2 gene. A comparative analysis of glycemic variability in the two groups was performed. Sensitivity and specificity of the cutoff value for the coefficient of variability as a diagnostic marker of MODY2 were also calculated.

Results: The pregnant women with GDM had significantly higher age and body mass index (BMI) than those with MODY2 (p<0.05). There were significant differences in venous fasting plasma glucose and glycated hemoglobin, with these parameters being higher in the pregnant women with MODY2 (p<0.05). In the patients with a  mutation in the GCK gene, hyperglycemia was diagnosed earlier and insulin therapy was started earlier during pregnancy than in those with GDM (p<0.05). The ROC analysis of the diagnostic accuracy of the variability coefficient showed that at the threshold CV (coefficient of variation) value of 20.8, the area under the curve was 0.742 (95% confidence intervals 0.597 to 0.888; p<0.005), with the sensitivity of 65% and the specificity of 65.4%.

Conclusion: The calculated sensitivity of 65% and specificity of 65.4% for the CV of 20.8 do not allow for its use as an independent selection criterion for subsequent confirmation of MODY2. However, its combination with the A.J. Chakera criteria (BMI<25 kg/m2 and fasting glucose≥5.5  mmol with 68%  sensitivity and 96%  specificity) allows to clarify the category of pregnant women with newly detected early hyperglycemia, to whom the search for mutations in the GCK gene should be recommended.

About the authors

M. A. Plekhanova

Moscow Regional Scientific Research Institute for Obstetrics and Gynecology

Author for correspondence.
Email: margarita_kr@list.ru
ORCID iD: 0000-0002-5322-1021

Margarita A. Plekhanova – MD, Endocrinologist, Outpatient Department

22a Pokrovka ul., Moscow, 101000

Russian Federation

F. F. Burumkulova

Moscow Regional Scientific Research Institute for Obstetrics and Gynecology

Email: fatima-burumkulova@yandex.ru
ORCID iD: 0000-0001-9943-0964

Fatima F. Burumkulova – MD, PhD, Leading Research Fellow

22a Pokrovka ul., Moscow, 101000

Russian Federation

V. A. Petrukhin

Moscow Regional Scientific Research Institute for Obstetrics and Gynecology

Email: petruhin271058@mail.ru
ORCID iD: 0000-0003-0460-3047

Vasily A. Petrukhin – MD, PhD, Professor, Director

22a Pokrovka ul., Moscow, 101000

Russian Federation

T. S. Budykina

Moscow Regional Scientific Research Institute for Obstetrics and Gynecology

Email: budyt@mail.ru
ORCID iD: 0000-0001-9873-2354

Tatiana S. Budykina – MD, PhD, Head of Clinical Diagnostic Laboratory

22a Pokrovka ul., Moscow, 101000

Russian Federation

A. E. Panov

Moscow Regional Scientific Research Institute for Obstetrics and Gynecology

Email: drpanov82@gmail.com
ORCID iD: 0000-0002-9362-0852

Anton E. Panov – MD, Research Fellow

22a Pokrovka ul., Moscow, 101000

Russian Federation

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Copyright (c) 2020 Plekhanova M.A., Burumkulova F.F., Petrukhin V.A., Budykina T.S., Panov A.E.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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