The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young

doi:10.1016/j.ajog.2015.04.037

American Journal of Obstetrics and Gynecology

Volume 213, Issue 2, August 2015, Pages 236.e1-236.e7

https://doi.org/10.1016/j.ajog.2015.04.037 Get rights and content

Objective

Women with maturity-onset diabetes of the young (MODY) are often first identified and diagnosed with diabetes during pregnancy. Genetics and hyperglycemia play an important role in determining fetal size in MODY pregnancies. The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations.

Study Design

A retrospective chart review of 37 women with a GCK/HNF-1α mutation was conducted. Data on variables such as birthweight, mode of delivery, and the treatment of hyperglycemia were available on 89 pregnancies.

Results

The birthweight in unaffected GCK offspring was significantly higher than in the affected GCK offspring (4.8 [4.1-5.2] kg vs 3.2 [3.1-3.7] kg; P = .01). Seven-point home blood glucose monitoring over a 7-day period in each trimester demonstrated higher fasting and postprandial glycemic excursions in the first trimester of GCK pregnancies when compared to HNF-1α pregnancies (fasting 104 [90-115] mg/dL vs 84 [77-88] mg/dL; P = .01 and postprandial 154 [135-196] mg/dL vs 111 [100-131] mg/dL; P = .04) despite insulin treatment. There was a higher percentage of miscarriages in the GCK group when compared to the HNF-1α MODY group (33.3% vs 14%; P = .07), which was similar to the background population. Insulin initiated at an early gestation appeared to lower the incidence of macrosomia in GCK unaffected offspring.

Conclusion

Hyperglycemia in HNF-1α pregnancies is easily managed with current insulin protocols; in contrast, glycemic excursions are difficult to manage in GCK pregnancies. There was an increased percentage of miscarriages in GCK pregnancies highlighting the importance of a diagnosis of GCK-MODY in women prior to conception and the necessity for preconception care.

Section snippets

Subjects

A total of 37 (n = 12, GCK; n = 25, HNF-1α) women participated in the study; these women were identified as part of the MODY cohort screening study in the Mater Hospital.¹⁷ The GCK mutations were p.D311fs, A378V, p.I293R, L146fs, D160N, and p.Y61X (6 pedigrees). The HNF-1α mutations were P379T, p.L502fs, V351fsdelG, c.1502_6 G>A, p.G292fs, S335X, Ser352fs, p.R159Q, p.R200Q, and P.E230fs (11 pedigrees).

We retrospectively studied the pregnancy outcome in these 37 women. The mutation status was

Clinical parameters

The clinical characteristics of the participants are contained in Table 1.

There was no significant difference in birthweight in GCK pregnancies when compared to HNF-1α pregnancies (3.9 [3.2-4.5] kg vs 3.6 [3.1-4] kg; P = .4). Insulin doses expressed in U/kg did not significantly differ between the groups throughout the trimesters (Figure 1). In both the GCK and the HNF-1α group 7 injections (3 short-acting insulin analogs and 4 neutral protamine hagedorn injections) were required in the

Comment

To date, publications on MODY in pregnancy have focused largely on fetal size as dictated by mutation status or the mode of treatment used to treat hyperglycemia during the pregnancy. To our knowledge, this is the first article to observe glycemic variability and detail fetal and neonatal outcomes in pregnancies complicated by MODY.

This is the first report on the clinical management of pregnancies complicated by HNF-1α MODY. We report that HNF-1α MODY is a relatively easy disorder to manage

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Cited by (36)

Maternal Diabetes
2023, Avery's Diseases of the Newborn
The incidence of diabetes in pregnancy is steadily rising in parallel with the rising incidence of obesity among pregnant patients. The current rate of diabetes in pregnancy is up to 9% with 80% to 90% of cases due to gestational diabetes. Pregnant patients with diabetes are at increased risk for fetal complications (such as congenital malformations, abnormal fetal growth, and stillbirth) and perinatal/neonatal complications (such as prematurity, respiratory distress, and metabolic abnormalities, including hypoglycemia and electrolyte derangements). Maternal complications include an increased risk for preeclampsia and need for cesarean delivery. Tight maternal glycemic control, achieved preconception and maintained throughout pregnancy, is key to optimizing short- and long-term maternal, fetal, and neonatal outcomes. Breastfeeding should be encouraged and supported as it may reduce some of the possible adverse effects of intrauterine programming in the context of maternal diabetes.
Management and Outcomes of Maturity-Onset Diabetes of the Young in Pregnancy
2019, Canadian Journal of Diabetes
Citation Excerpt :
Complication rates were also higher in the noninsulin-treated group compared with the insulin-treated group (37.5% vs 0%). These complications included neural tube defects, shoulder dystocia and prolonged neonatal hypoglycemia (16). There is 1 case report in which insulin was used and resulted in SGA in the case of an affected fetus.
Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders that accounts for 1% to 5% of diabetes. The most common mutations are those in the hepatocyte nuclear factor-1-alpha (HNF-1-alpha) and in the glucokinase (GCK) genes. Although management of MODY is well established, no guidelines currently exist for management during pregnancy. Both maternal glycemic control and fetal mutation status are factors that may influence outcomes during pregnancy. The primary aim of this project was to describe cases of MODY during pregnancy to highlight the clinical implications of management of this disorder during pregnancy. The Ottawa Hospital is the primary referral centre for high-risk obstetrical patients, including those with diabetes in pregnancy, in Ottawa, Canada. Referrals between 2008 and 2018 were reviewed and a case series of three women and five pregnancies is described. Together with the illustrative cases, a literature review of MODY in pregnancy is used to highlight clinical considerations unique to MODY in pregnancy. We describe 5 pregnancies with MODY-2 (GCK mutation) and MODY 3 (HNF-1-alpha mutation). Important issues identified included monitoring of fetal growth and individualization of maternal glycemic control, particularly in cases where fetal mutation status is unknown. Management of MODY in pregnancy is challenging and there is little evidence to guide recommendations. Fetal growth can be used to guide management of maternal glycemic targets when fetal mutation status is unknown.
Le diabète de la maturité apparaissant chez le jeune (MODY) constitue un groupe d'anomalies monogéniques qui représente de 1 % à 5 % des types de diabète. Les mutations les plus fréquentes sont celles des gènes codant pour le hépatocyte nucléaire facteur 1-alpha (HNF-1-alpha) et pour la glucokinase (GCK). Bien que la prise en charge du MODY soit bien établie, il n'existe actuellement aucune ligne directrice sur sa prise en charge durant la grossesse. La régulation de la glycémie maternelle et le statut mutationnel du fœtus sont des facteurs qui peuvent influencer les issues de la grossesse. L'objectif principal de la présente étude était de décrire les cas de MODY durant la grossesse pour démontrer les conséquences cliniques de la prise en charge de cette anomalie durant la grossesse. L’Hôpital d’Ottawa est le principal centre, à Ottawa, au Canada, qui offre des services de consultation en obstétrique aux patientes exposées à un risque élevé, y compris aux patientes diabétiques durant leur grossesse. Nous avons passé en revue les consultations entre 2008 et 2018, et nous avons décrit des séries de cas de 3 femmes et de 5 grossesses. Conjointement aux cas cités en exemple, une revue de littérature du MODY durant la grossesse est utilisée pour faire valoir les considérations cliniques propres au MODY durant la grossesse. Nous décrivons 5 grossesses de femmes ayant le MODY-2 (mutation codant pour la GCK) et le MODY-3 (mutation codant pour le HNF-1-alpha). Les points importants sont la surveillance de la croissance fœtale et l'individualisation de la régulation de la glycémie maternelle, notamment dans les cas où l'on ignore le statut mutationnel du fœtus. La prise en charge du MODY durant la grossesse est difficile. Il existe peu de données probantes pour mener à des recommandations. La croissance fœtale peut être utilisée pour orienter la prise en charge des valeurs cibles de la glycémie maternelle lorsqu'on ignore l’état mutationnel du fœtus.
Maternal Diabetes
2018, Avery's Diseases of the Newborn: Tenth Edition
- •
  The incidence of diabetes in pregnancy is steadily rising, likely in parallel with the rising incidence of obesity among women of reproductive age.
- •
  Women with diabetes are at increased risk for fetal complications (such as congenital malformations, fetal growth abnormalities, and stillbirth) and perinatal/neonatal complications (such as prematurity, respiratory distress, and metabolic abnormalities including hypoglycemia and electrolyte derangements).
- •
  Good maternal glycemic control achieved preconception and maintained throughout pregnancy is key to optimizing fetal and neonatal outcomes.
- •
  Breastfeeding should be strongly encouraged and supported as it may reduce some of the possible adverse effects of intrauterine programming in the context of maternal diabetes.
Maternal Diabetes
2017, Avery's Diseases of the Newborn, Tenth Edition
- •
  The incidence of diabetes in pregnancy is steadily rising, likely in parallel with the rising incidence of obesity among women of reproductive age.
- •
  Women with diabetes are at increased risk for fetal complications (such as congenital malformations, fetal growth abnormalities, and stillbirth) and perinatal/neonatal complications (such as prematurity, respiratory distress, and metabolic abnormalities including hypoglycemia and electrolyte derangements).
- •
  Good maternal glycemic control achieved preconception and maintained throughout pregnancy is key to optimizing fetal and neonatal outcomes.
- •
  Breastfeeding should be strongly encouraged and supported as it may reduce some of the possible adverse effects of intrauterine programming in the context of maternal diabetes.
Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing
2023, Diabetologia
Maternal and Infant Outcomes in GCK-MODY Complicated by Pregnancy
2023, Journal of Clinical Endocrinology and Metabolism

View all citing articles on Scopus

: This study was supported by grant number HPF-2013-459 from the Health Research Board of Ireland awarded to S.B.

: The authors report no conflict of interest.

: Cite this article as: Bacon S, Schmid J, McCarthy A, et al. The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young. Am J Obstet Gynecol 2015;213:236.e1-7.

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ResearchObstetricsThe clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young

Objective

Study Design

Results

Conclusion

Section snippets

Subjects

Clinical parameters

Comment

Diabetes Res Clin Pract

Eur J Obstet Gynecol Reprod Biol

Am J Obstet Gynecol

Diabetes Metab

Best Pract Res Clin Endocrinol Metab

Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young

Diabetologia

Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia

JAMA

Chronic mild hyperglycemia in GCK-MODY patients does not increase carotid intima-media thickness

Int J Endocrinol

Chronic diabetic complications in patients with MODY3 diabetes

Diabetologia

Diabetes complications in NIDDM kindreds linked to the MODY3 locus on chromosome 12q

Diabetes Care

A high prevalence of glucokinase mutations in gestational diabetic subjects selected by clinical criteria

Diabetologia

The 0.1% of the population with glucokinase monogenic diabetes can be recognized by clinical characteristics in pregnancy: the Atlantic Diabetes in Pregnancy cohort

Diabetes Care

Identification of glucokinase mutations in subjects with gestational diabetes mellitus

Diabetes

Research
Obstetrics
The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young