Maturity-Onset Diabetes of the Young in Children With Incidental Hyperglycemia:

Lorini, Renata; Klersy, Catherine; d’Annunzio, Giuseppe; Massa, Ornella; Minuto, Nicola; Iafusco, Dario; Bellanné‐Chantelot, Christine; Frongia, Anna Paola; Toni, Sonia; Meschi, Franco; Cerutti, Fránco; Barbetti, Fabrizio

doi:10.2337/dc08-2018

Cited by 102 publications

(67 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Prevalence of GCK-MODY in Children and Adults With Incidental Hyperglycemia GCK-MODY is a very common cause (23-65%) of incidental hyperglycemia in children, especially when the fasting glucose is persistently above 5.5 mmol/L (29,(40)(41)(42)(43)(44). Awareness of such high GCK-MODY prevalence rates in children with mild fasting hyperglycemia will aid early, correct diagnosis and management.…”

Section: Prevalence Of Gck-mody In Modymentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

Section: Prevalence Of Gck-mody In Modymentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The disease onset is usually before 25 years and demonstrates a (Lorini et al 2009), 62% in Germany and Austria (Schober et al 2009), 56% in French (Froguel et al 1993), 41% in Spanish (Barrio et al 2002). However, MODY2 is rarely reported in Asian, with only 1% in Hong Kong Chinese (Xu et al 2005), 1% in Japanese (Eto et al 1993), and 2.5% in Korean (Hwang et al 2006).…”

Section: Discussionmentioning

confidence: 89%

Insight into the biochemical characteristics of a novel glucokinase gene mutation

et al. 2010

View full text Add to dashboard Cite

Glucokinase (GCK) acts as a glucose sensor and regulates β-cell insulin secretion. The heterozygous mutations in the gene encoding GCK cause a reduction of the enzyme activity, which results in a monogenic form of diabetes, maturity-onset diabetes of the young. In the present study, we identified and functionally characterized a novel missense mutation in the GCK gene, which results in a protein mutation Glu(339)→Lys (E339K), from a Chinese family with hyperglycemia. The same GCK mutation that co-segregated with diabetes phenotype was identified in five members of this family but was not found in 200 healthy control individuals. We expressed and affinity-purified the GCK proteins from bacterial expression system that carries mutation (E339K) and fused to glutathione S-transferase. The expressed GCK protein was subjected to the measurement of its biochemical effects of the missense mutation on GCK activity. Our results showed that the mutation reduced the GCK protein yield. The enzymatic kinetics and the thermal stability analysis on the recombinant GCK proteins revealed that the mutation inactivates enzyme kinetics and severely impaired the GCK protein stability.

show abstract

“…Among the thirteen MODY genes identified, two subtypes, GCK-MODY and HNF1A-MODY, account for most of cases (1). The prevalence of GCK-MODY has been reported higher in Southern Europe (2), while HNF1A-MODY is the most common MODY subtype in Northern Europe (3). This difference might be attributable to the clinical setting in which genetic screening is performed, especially when pediatric and adult diabetes clinics are distinct entities.…”

mentioning

confidence: 82%

Low Prevalence of HNF1A Mutations After Molecular Screening of Multiple MODY Genes in 58 Italian Families Recruited in the Pediatric or Adult Diabetes Clinic From a Single Italian Hospital

et al. 2014

Self Cite

View full text Add to dashboard Cite

Maturity-Onset Diabetes of the Young in Children With Incidental Hyperglycemia:

Cited by 102 publications

References 16 publications

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

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

Insight into the biochemical characteristics of a novel glucokinase gene mutation

Low Prevalence of HNF1A Mutations After Molecular Screening of Multiple MODY Genes in 58 Italian Families Recruited in the Pediatric or Adult Diabetes Clinic From a Single Italian Hospital

Contact Info

Product

Resources

About