High prevalence of a missense mutation of the glucokinase gene in gestational diabetic patients due to a founder-effect in a local population

Saker, P. J.; Hattersley, Andrew T.; Barrow, B A; Hammersley, M S; McLellan, J.; Lo, Yen-Li; Olds, R.J.; Gillmer, M. D. G.; Holman, R R; Turner, R. C.

doi:10.1007/s001250050577

Cited by 61 publications

(56 citation statements)

References 20 publications

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“…All known forms of MODY are primarily linked with pancreatic ␤-cell dysfunction. Previous studies have shown that mutations in the GCK (MODY2) gene could explain ϳ5-6% of GD in different populations (12)(13)(14). In our previous study of early onset diabetes, 11 of 29 diabetic women with MODY3 (38%) had had GDM (15).…”

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confidence: 85%

Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus

et al. 2002

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OBJECTIVE -To investigate whether genetic susceptibility to type 1 diabetes or maturityonset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODS -We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum.RESULTS -There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n ϭ 82) or healthy control subjects (n ϭ 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1␣ gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum.CONCLUSIONS -MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes. Diabetes Care 25:68 -71, 2002

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confidence: 85%

Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus

et al. 2002

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“…Approximately 2% (range 0-6%) of women with a diagnosis of gestational diabetes mellitus have a heterozygous GCK gene mutation (23,34,(46)(47)(48)(49)(50)(51)(52)(53) (16,19,55). The raised fasting glucose is not correlated with BMI (54) so occurs to a similar degree in both slim and obese individuals.…”

Section: Prevalence Of Gck-mody In Gestational Diabetes Mellitusmentioning

confidence: 99%

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

et al. 2015

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Glucokinase–maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in ∼1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10–60%): persistent incidental childhood hyperglycemia (10–60%) and gestational diabetes mellitus (1–2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4–8.3 mmol/L, HbA1c range 5.8–7.6% [40–60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.

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“…Women with mutations in GCK [12][13][14][15][16][17] or HNF1A [16,18] often present with GDM. In addition, mutations in IPF1 have been reported in women with GDM [16,19].…”

Section: Introductionmentioning

confidence: 99%

Common variants in MODY genes increase the risk of gestational diabetes mellitus

et al. 2006

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High prevalence of a missense mutation of the glucokinase gene in gestational diabetic patients due to a founder-effect in a local population

Cited by 61 publications

References 20 publications

Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus

Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

Common variants in MODY genes increase the risk of gestational diabetes mellitus

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