AI Article Synopsis

  • The study examined fetal and maternal outcomes in pregnant women with Glucokinase-Maturity onset diabetes of the young (GCK-MODY), focusing on 99 pregnancies among 34 affected women.
  • A higher percentage of offspring without the GCK mutation had increased birth weights, were more likely to be classified as large for gestational age (LGA), and necessitated caesarean sections compared to affected offspring.
  • The findings suggest that fetal genetics play a crucial role in determining birth weight, and more research is needed on targeted therapies utilizing pre-pregnancy diagnosis and continuous glucose monitoring.

Article Abstract

Aims: To determine the fetal and maternal outcomes in pregnant women with Glucokinase-Maturity onset diabetes of the young (GCK-MODY).

Methods: We studied the obstetric and perinatal outcomes in 99 pregnancies of 34 women with GCK-MODY. The mutation status of the offspring was known in 29 and presumed in 33. Clinical outcomes were determined and compared between affected (n = 39) and unaffected (n = 23) offspring.

Results: 59% of pregnancies were treated with diet alone and 41% received insulin. Birthweight, percentage of large for gestational age (LGA) and caesarean section (CS) in GCK-unaffected offspring was significantly higher than in GCK-affected offspring (4.0 ± 0.7 vs. 3.4 ± 0.4 kg, p = 0.001), 15 (65%) vs. 5(13%) (p = 0.00006) and 17 (74%) vs. 11 (28%) (p = 0.001), respectively. We observed an earlier gestational age at delivery on insulin in unaffected offspring (38.3 ± 1.0 vs. 39.5 ± 1.5 weeks, p = 0.03) with no significant change in LGA (9 (82%) vs. 6 (50%); p = 0.12), and a higher rate of CS (8 [73%] vs. 3 [11%]; p < 0.001), and no change in small for gestational age (0 [0%] vs. 4 [14%]; p = 0.30) in affected offspring.

Conclusion: Insulin therapy in unaffected offspring did not reduce LGA and was associated with earlier gestational age at delivery. Insulin treatment in GCK-affected offspring was associated with an increased incidence of CS, but did not adversely affect fetal outcome. Fetal genotype determines birthweight rather than treatment. Pre-pregnancy diagnosis of GCK-MODY, use of continuous glucose monitoring and non-invasive fetal genotyping may enable further investigation of targeted therapy in this condition.

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Source
http://dx.doi.org/10.1111/dme.14488DOI Listing

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Article Synopsis
  • Monogenic diabetes, accounting for 5% of hyperglycemia cases, includes Maturity Onset Diabetes of the Young (MODY), with GCK-MODY being a common subtype caused by a glucokinase gene mutation.
  • GCK-MODY typically results in mild, asymptomatic high fasting glucose levels and has low risks of complications; the primary treatment focuses on maintaining a healthy lifestyle.
  • The report highlights a case of a woman diagnosed with GCK-MODY during her pregnancy with twins, emphasizing the importance of genetic testing and how the diagnosis brought relief and encouraged positive lifestyle changes for the whole family.
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Women with maturity-onset diabetes of the young (MODY) need tailored antenatal care and monitoring of their offspring. Each MODY subtype has different implications for glycaemic targets, treatment choices and neonatal management. Hyperglycaemia of MODY is often first diagnosed in adolescence or early adulthood and therefore is clinically relevant to pregnant women.

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Background: Mutations in the gene cause Maturity Onset Diabetes of the Young (GCK-MODY) by impairing glucose-sensing in pancreatic beta cells. During pregnancy, managing this type of diabetes varies based on fetal genotype. Fetuses carrying a mutation can derive benefit from moderate maternal hyperglycemia, stimulating insulin secretion in fetal islets, whereas this may cause macrosomia in wild-type fetuses.

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Pregnancy in women with monogenic diabetes is potentially complex, with significant implications for both maternal and fetal health. Among these, maturity-onset diabetes of the young (MODY) stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice. Each subtype of MODY requires a distinct approach tailored to the pregnancy, diverging from management strategies in non-pregnant individuals.

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Aims/hypothesis: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound.

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