Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents

Feigerlová, Eva; Průhová, Štěpánka; Dittertová, L; Lebl, Jan; Pintérová, Daniela; Kološtová, Katarína; Černá, Marie; Pedersen, Oluf; Hansen, Torben

doi:10.1007/s00431-006-0106-3

Cited by 55 publications

(41 citation statements)

References 21 publications

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“…Selecting participants based on age <45 years and BMI <27 kg/m 2 would have missed all of those with GCK-MODY. Our data support earlier work suggesting that GCK-MODY is a common cause of childhood and adolescent hyperglycaemia and that early screening (<25 years) would facilitate the identification of such individuals [7,8]. In the age group we studied, the low GCK-MODY prevalence (<1%) is unlikely to affect the design and statistical power of diabetes intervention trials.…”

supporting

confidence: 72%

“…Our results are in contrast to studies performed in children and adolescents with asymptomatic hyperglycaemia in which GCK mutations have been identified in 43% (35/82) of individuals [7]. Children and adolescents with hyperglycaemia are more likely to have a monogenic explanation for their condition than are older individuals (>35 years), who are more likely to be on a trajectory for type 2 diabetes.…”

contrasting

confidence: 56%

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Prevalence of GCK mutations in individuals screened for fasting hyperglycaemia

et al. 2008

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supporting

confidence: 72%

contrasting

confidence: 56%

Prevalence of GCK mutations in individuals screened for fasting hyperglycaemia

et al. 2008

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“…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%

“…If they develop these more common types of diabetes, they will be at risk for complications and are likely to require additional follow-up and treatment (40,90). However, achieving glycemia less than the levels found in untreated GCK-MODY is extremely difficult in patients with type 1 or type 2 diabetes who also have a GCK mutation [M.H.S.…”

Section: Follow-up and Testing For People With Gck-modymentioning

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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“…Patients with heterozygous loss-of-function GCK mutations are not diagnosed until incidental testing reveals hyperglycaemia 12 . If identified in childhood, this disease condition can be misdiagnosed as T1D; if in adult life as T2D, and if detected during pregnancy as gestational diabetes mellitus (GDM).…”

Section: Glucokinase Modymentioning

confidence: 99%

Genetic Basis of Monogenic Diabetes

Radha¹,

Mohan²

2017

Current Science

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Advances in the understanding of monogenic causes of diabetes and the discovery of single-gene mutations responsible for different phenotypes have greatly increased our knowledge of -cell physiology. Such advances have had implications for the individual patient diagnosed with the specific monogenic cause of diabetes, especially in maturity onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM). Genetic diagnosis of MODY is also likely to have important prognostic and therapeutic implications in majority of the patients with confirmed HNF1A and HNF4A mutations. Genetic screening and analyses have helped several neonatal infants carrying mutations in the KCNJ11 and ABCC8 genes to shift from insulin treatment to oral sulphonylurea drugs. The progress in genomics of monogenic diabetic forms has helped in translating the discoveries from bench to bedside in clinical care. Therefore, there is an urgent need to incorporate genetic testing for the genes implicated in monogenic diabetes like MODY and NDM in the diabetes clinics. Discoveries in genetic research methodology and understanding of genetic etiology will have great translational implications for disease treatment and follow-up.

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Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents

Cited by 55 publications

References 21 publications

Prevalence of GCK mutations in individuals screened for fasting hyperglycaemia

Prevalence of GCK mutations in individuals screened for fasting hyperglycaemia

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

Genetic Basis of Monogenic Diabetes

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