Evaluation of pregnancy outcomes in women with GCK‐MODY

Tinoco, Cristina López; Lechuga, Begoña Sánchez; Bacon, Siobhán; Colclough, Kevin; Ng, Nicholas Beng Hui; Wong, Eleanor; Goulden, Eirena L.; Edwards, J.R.G.; Fleming, Aileen; Byrne, B; Byrne, Maria

doi:10.1111/dme.14488

Cited by 14 publications

(21 citation statements)

References 28 publications

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“…According to the Pedersen hypothesis (48), this suggested that accelerated fetal growth was induced by increased fetal insulin secretion by non-affected fetuses in response to maternal hyperglycemia, and that fetal growth was normal in affected fetuses since their insulin secretion was set at the same level as their mother's. Observational studies have consistently confirmed this report (41,42,(49)(50)(51)(52), and showed that the frequency of macrosomia (birthweight > 4000 g) and/or of LGA offspring were high (33-65%) in the first situation, as compared to the latter (4-13%, i.e. the expected rate of LGA in the general population) (Table 1).…”

Section: Unaffected Offspring Of Mothers With Gck-mody Are At High Risk Of Macrosomiasupporting

confidence: 66%

“…The Rate of Miscarriage Would Be Expected to Be Increased Given the Blood Glucose and HbA 1c Levels Observed in GCK-MODY Women It has been reported to be increased compared to that of the general population (33% of 56 pregnancies) in one study (40), but similar to the general population rate in a further study by the same group on a larger population (17% of 119 pregnancies) (41), and in an additional independent study (19% of 128 pregnancies) (42).…”

Section: Risks Associated With Pregnancy In Women With Gck-modymentioning

confidence: 74%

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Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

et al. 2022

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Heterozygous loss-of-function variants of the glucokinase (GCK) gene are responsible for a subtype of maturity-onset diabetes of the young (MODY). GCK-MODY is characterized by a mild hyperglycemia, mainly due to a higher blood glucose threshold for insulin secretion, and an up-regulated glucose counterregulation. GCK-MODY patients are asymptomatic, are not exposed to diabetes long-term complications, and do not require treatment. The diagnosis of GCK-MODY is made on the discovery of hyperglycemia by systematic screening, or by family screening. The situation is peculiar in GCK-MODY women during pregnancy for three reasons: 1. the degree of maternal hyperglycemia is sufficient to induce pregnancy adverse outcomes, as in pregestational or gestational diabetes; 2. the probability that a fetus inherits the maternal mutation is 50% and; 3. fetal insulin secretion is a major stimulus of fetal growth. Consequently, when the fetus has not inherited the maternal mutation, maternal hyperglycemia will trigger increased fetal insulin secretion and growth, with a high risk of macrosomia. By contrast, when the fetus has inherited the maternal mutation, its insulin secretion is set at the same threshold as the mother’s, and no fetal growth excess will occur. Thus, treatment of maternal hyperglycemia is necessary only in the former situation, and will lead to a risk of fetal growth restriction in the latter. It has been recommended that the management of diabetes in GCK-MODY pregnant women should be guided by assessment of fetal growth by serial ultrasounds, and institution of insulin therapy when the abdominal circumference is ≥ 75th percentile, considered as a surrogate for the fetal genotype. This strategy has not been validated in women with in GCK-MODY. Recently, the feasibility of non-invasive fetal genotyping has been demonstrated, that will improve the care of these women. Several challenges persist, including the identification of women with GCK-MODY before or early in pregnancy, and the modalities of insulin therapy. Yet, retrospective observational studies have shown that fetal genotype, not maternal treatment with insulin, is the main determinant of fetal growth and of the risk of macrosomia. Thus, further studies are needed to specify the management of GCK-MODY pregnant women during pregnancy.

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Section: Unaffected Offspring Of Mothers With Gck-mody Are At High Risk Of Macrosomiasupporting

confidence: 66%

Section: Risks Associated With Pregnancy In Women With Gck-modymentioning

confidence: 74%

Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

et al. 2022

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“…37 The birth weight for the infant in Case 2 was normal, despite her mother's history of diabetes diagnosed after screening in a previous pregnancy. Therefore, for a hyperglycemic infant of normal or low birth weight born to a mother with GDM, particularly where maternal hyperglycemia has failed to respond to insulin treatment in pregnancy 9,38 and persists postpartum, GCK-MODY is an important consideration. Neonatal hypoglycemia and macrosomia may be evident in the infant who has not inherited the same GCK mutation as their mother, 9 so a high birth weight and history of neonatal hypoglycemia in siblings may also provide a useful clue to the diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Identification ofGCK‐maturity‐onset diabetes of the young in cases of neonatal hyperglycemia: A case series and review of clinical features

Hughes

Franco

Globa³

et al. 2021

Pediatr Diabetes

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Heterozygous mutations in GCK result in a persistent, mildly raised glucose from birth, but it is usually diagnosed in adulthood as maturity-onset diabetes of the young (MODY), where hyperglycemia is often an incidental finding. The hyperglycemia of GCK-MODY is benign and does not require treatment, but is important to be aware of, particularly in females where it has implications for managing pregnancy. We present three cases of neonatal hyperglycemia resulting from a heterozygous mutation in GCK, illustrating its clinical presentation and evolution in early life. In summary, as with adults, neonatal hyperglycemia is an incidental finding, does not require treatment and has no adverse consequences for health. Neonates and their parents should be referred for genetic testing to confirm the diagnosis, avoid a label of diabetes and enable pregnancy counseling for females found to be affected.

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“…LGA-Rate (LGA: Large for Gestational Age) nicht reduzieren. Sie führte jedoch zu einer früheren Geburt und zu mehr neonatalen Hypoglykämien [12]. Ähnliches zeigte sich im US-amerikanischen MODY-Register [13].…”

Section: Diagnoseunclassified

Prädisposition/Phänotypen des Gestationsdiabetes mellitus

Kleinwechter¹,

Demandt²,

Nolte³

2021

Diabetologie und Stoffwechsel

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Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. In Germany, the prevalence in 2019 was 6.8 %. The predisposition includes obesity, advanced age, familial diabetes burden, unfavourable lifestyle, e. g. lack of exercise and an unhealthy diet, as well as previous GDM. These factors are largely identical to the predisposition to type 2 diabetes mellitus. There is no uniform GDM phenotype; in addition to pregnant women with insulin resistance, there are those with beta-cell dysfunction and mixed types. Once pregnancy has been diagnosed, later GDM can be reduced by 27–55 % through ergometer training, a Mediterranean diet with supplements of olive oil and pistachios, and a more complex accompanying program. After pregnancy with GDM, women have a 6.5–10-fold increased risk of converting to type 2 diabetes within 5–25 years and a 2-fold increased risk of cardiovascular complications after 10 years. Only 40 % of women take part in follow-up care. Intensive lifestyle intervention with diet, exercise and weight control could effectively reduce the risk of diabetes in women with prediabetes. In addition, the use of metformin could be considered in high-risk cases. Hyperglycaemia in pregnancy is programming the children’s risk of overweight and obesity via epigenetic effects, which could be further increased by unfavourable familial lifestyle factors. Prevention programs would only be effective if health policy measures are implemented in addition to individual preventive programs.

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Evaluation of pregnancy outcomes in women with GCK‐MODY

Cited by 14 publications

References 28 publications

Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

Identification ofGCK‐maturity‐onset diabetes of the young in cases of neonatal hyperglycemia: A case series and review of clinical features

Prädisposition/Phänotypen des Gestationsdiabetes mellitus

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