Abstract
Aims
Many authors do not recommend hypoglycemic treatment during pregnancy in women affected by monogenic diabetes due to heterozygous glucokinase (GCK) mutations (MODY 2) in case of affected fetus, because maternal hyperglycemia would be necessary to achieve a normal birthweight. We aimed to evaluate differences in birthweight between MODY 2 affected children according to the parent who carried the mutation.
Methods
We retrospectively studied 48 MODY 2 affected children, whose mothers did not receive hypoglycemic treatment during pregnancy, divided into two groups according to the presence of the mutation in the mother (group A) or in the father (group B). Data were extracted from the database of the Regional Centre of Pediatric Diabetology of the University of Campania, Naples, collected from 1996 to 2016. We analyzed birthweight and centile birthweight.
Results
Percentage of small for gestational age was significantly higher in group B than in group A. We found three large for gestational age in the group that inherited the deficit from the mother, all with the same novel GCK mutation (p.Lys458-Cys461del).
Conclusions
We hypothesize that not all MODY 2 affected fetuses need the same levels of hyperglycemia to have an appropriate growth, maybe because different kinds of GCK mutations may result in different phenotypes. Consequently, a “tailored therapy” of maternal hyperglycemia, based on fetal growth frequently monitored through ultrasounds, is essential in MODY 2 pregnancies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chakera AJ, Steele AM, Gloyn AL et al (2015) Recognition and management of individuals with hyperglycemia because of a heterozygous glucokinase mutation. Diabetes Care 38(7):1383–1392
Bacon S, Schmid J, McCarthy A et al (2015) The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young. Am J Obstet Gynecol 213(2):236.e1–236.e7
Colom C, Corcoy R (2010) Maturity onset diabetes of the young and pregnancy. Best Pract Res Clin Endocrinol Metab 24(4):605–615
Hattersley AT, Beards F, Ballantyne E, Appleton M, Harvey R, Ellard S (1998) Mutations in the glucokinase gene of the fetus result in reduced birth weight. Nat Genet 19(3):268–270
Barrio R, Bellanné-Chantelot C, Moreno JC, Morel V, Calle H, Alonso M, Mustieles C (2002) Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families. J Clin Endocrinol Metab 87(6):2532–2539
Shehadeh N, Bakri D, Njølstad PR, Gershoni-Baruch R (2005) Clinical characteristics of mutation carriers in a large family with glucokinase diabetes (MODY2). Diabet Med 22(8):994–998
Spyer G, Macleod KM, Shepherd M, Ellard S, Hattersley AT (2009) Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation. Diabet Med 26(1):14–18
Spyer G, Hattersley AT, Sykes JE, Sturley RH, MacLeod KM (2001) Influence of maternal and fetal glucokinase mutations in gestational diabetes. Am J Obstet Gynecol 185(1):240–241
Iafusco D, Galderisi A, Lombardo F et al (2011) All classifications not built on pathogenesis become inadequate sooner or later. Diabetologia 54(6):1583–1584
Bertino E, Spada E, Occhi L et al (2010) Neonatal anthropometric charts: the Italian neonatal study compared with other European studies. J Pediatr Gastroenterol Nutr 51:353–361
Capuano M, Garcia-Herrero CM, Tinto N et al (2012) Glucokinase (GCK) mutations and their characterization in MODY2 children of southern Italy. PLoS One 7(6):e38906
Jenner Z, O’Neil Dudley AE, Mendez-Figueroa H, Ellis VS, Chen H, Chauhan SP (2017) Morbidity associated with fetal macrosomia among women with diabetes mellitus. Am J Perinatol. https://doi.org/10.1055/s-0037-1608811
Bulletins—Obstetrics, American College of Obstetricians and Gynecologists’ Committee on Practice (2016) Practice bulletin no. 173: fetal macrosomia. Obstet Gynecol 128(5):e195–e209
Ashworth A (1998) Effects of intrauterine growth retardation on mortality and morbidity in infants and young children. Eur J Clin Nutr 52(Suppl 1):S34–S41
International Association of Diabetes and Pregnancy Study Group Consensus Panel (2010) Internantional association of diabetes and pregnancy study group recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33(3):676–682
Barbour LA, Hernandez TL (2018) Maternal non-glycemic contributors to fetal growth in obesity and gestational diabetes: spotlight on lipids. Curr Diab Rep 18(6):37
Spégel P, Ekholm E, Tuomi T, Groop L, Mulder H, Filipsson K (2013) Metabolite profiling reveals normal metabolic control in carriers of mutations in the glucokinase gene (MODY2). Diabetes 62(2):653–661
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent
Informed consent for anonymous use of clinical data has been obtained from patients or from their parents, when minors.
Human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the responsible committee of human experimentation (institutional and national) and with the 1975 Helsinki declaration, as revised in 2008.
Additional information
Managed by Antonio Secchi.
Rights and permissions
About this article
Cite this article
Bitterman, O., Tinto, N., Franzese, A. et al. Glucokinase deficit and birthweight: does maternal hyperglycemia always meet fetal needs?. Acta Diabetol 55, 1247–1250 (2018). https://doi.org/10.1007/s00592-018-1198-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00592-018-1198-8