ISPAD Clinical Practice Consensus Guidelines 2006?2007 The diagnosis and management of monogenic diabetes in children

Hattersley, Andrew; Bruining, Jan; Shield, Julian P H; Njølstad, Pål R.; Donaghue, Kim C.

doi:10.1111/j.1399-5448.2006.00217.x

Cited by 120 publications

(85 citation statements)

References 61 publications

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“…As tests for MODY mutations are still not widely available and can be expensive, it is recommended that these tests be performed when they are likely to be positive and alter the management 7. We used the clinical phenotype and biochemical tests to guide the mutation analysis, which confirmed the diagnosis of HNF-1a MODY.…”

Section: Discussionmentioning

confidence: 99%

Response to oral gliclazide in a pre-pubertal child with hepatic nuclear factor-1 alpha maturity onset diabetes of the young

Habeb

George

Hattersley

2011

Annals of Saudi Medicine

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The term “maturity onset diabetes of the young” (MODY) describes a heterogeneous group of monogenic diabetes of which hepatic nuclear factor-1 alpha (HNF-1α) MODY is the most common. Patients with HNF-1α mutations typically present after puberty, and oral sulfonylureas (SU) have been shown to be effective in adults with this condition. A 7-year-old boy presented with asymptomatic hyperglycemia ranging between 6.2 and 10.1 mmol/L and glycosuria for nearly a year. The child's initial HbA1c was 6.9% and the pancreatic Islet cell autoantibodies were negative. His response to the oral glucose tolerance test (OGTT) showed a large increment of glucose from basal level of 7.7 to 21.1 mmol/L in 120 min. The mild presentation, family history, and negative autoantibodies were suggestive of HNF-1α MODY, which was confirmed by mutation analysis. Initial management with diet alone was not sufficient, but he responded well to 20 mg oral gliclazide once a day with an improvement of HbA1C from 7.2% to 6.5% within 3 months of treatment. The case is an illustration of the clinical utility of molecular genetic tests in the management of childhood diabetes.

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Section: Discussionmentioning

confidence: 99%

Response to oral gliclazide in a pre-pubertal child with hepatic nuclear factor-1 alpha maturity onset diabetes of the young

Habeb

George

Hattersley

2011

Annals of Saudi Medicine

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“…Neonatal diabetes (ND), or diabetes developing within the first few weeks or months of life, is a very rare condition with an incidence of 1 in 400,000 to 500,000 live births (6). Recent studies have shown that ND can result from abnormalities of an imprinted region of chromosome 6q24 and mutations in the genes encoding the glycolytic enzyme, glucokinase, and the two protein subunits (Kir6.2 and SUR1) of the ATP-sensitive potassium channel of the pancreatic ␤ cell (2,7). In addition, mutations in other genes (IPF1, PTF1A, FOXP3, GLIS3, TCF2, EIF2AK3) can lead to multisystem diseases that include ND (2).…”

mentioning

confidence: 99%

“…Recent studies have shown that ND can result from abnormalities of an imprinted region of chromosome 6q24 and mutations in the genes encoding the glycolytic enzyme, glucokinase, and the two protein subunits (Kir6.2 and SUR1) of the ATP-sensitive potassium channel of the pancreatic ␤ cell (2,7). In addition, mutations in other genes (IPF1, PTF1A, FOXP3, GLIS3, TCF2, EIF2AK3) can lead to multisystem diseases that include ND (2). As a result of genetic studies, the view has emerged that ND is primarily a genetic disorder and not a congenital form of type 1 diabetes with a cutoff at around 6 months (8,9).…”

mentioning

confidence: 99%

“…Genetic factors play an important role in the development of diabetes with some forms resulting from mutations in a single gene. Although monogenic forms of diabetes are collectively relatively uncommon, the identification of the underlying genetic defects has provided important insights into pancreatic development and the control of pancreatic ␤ cell function and improvements in diagnosis and treatment (1)(2)(3). Moreover, common variation in the same genes that can cause monogenic forms of diabetes can affect the risk of developing the common polygenic forms (4,5).…”

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confidence: 99%

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Insulin gene mutations as a cause of permanent neonatal diabetes

Støy

Edghill

Flanagan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

501

478

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We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with ␤ cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially ␤ cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of ␤ cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder.endoplasmic reticulum stress ͉ insulin biosynthesis ͉ disulfide bonds ͉ unfolded protein response

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“…There is extensive evidence that C-peptide can be used to differentiate between the classification of Type 1 diabetes and Type 2 diabetes [6][7][8][9][10] . C-peptide is a good candidate biomarker to differentiate patients with Maturity Onset Diabetes of the Young (MODY) from Type 1 diabetes.…”

Section: C-peptide and Differentiating Subtypes Of Diabetesmentioning

confidence: 99%

Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function

McDonald

Perry

2016

Methods in Molecular Biology

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SUMMARYC-peptide is a protein secreted by the pancreatic beta cells in equimolar quantities with insulin, following the cleavage of proinsulin into insulin. Measurement of C-peptide is used as a surrogate marker of endogenous insulin secretory capacity. Assessing C-peptide levels can be useful in classifying the sub-type of diabetes as well as assessing potential treatment choices in the management of diabetes.Standard measures of C-peptide involve blood samples collected either fasted or, most often, after a fixed stimulus (such as oral glucose, mixed meal or IV glucagon). Despite the established clinical utility of blood C-peptide measurement, its widespread use is limited. In many instances this is due to perceived practical restrictions associated with sample collection.Urine C-peptide measurement is an attractive non-invasive alternative to blood measures of beta-cell function. Urine C-peptide creatinine ratio measured in a single post stimulated sample has been shown to be a robust, reproducible measure of endogenous C-peptide which is stable for three days at room temperature when collected in boric acid. Modern high sensitivity immunoassay technologies have facilitated measurement of C-peptide down to single picomolar concentrations.

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ISPAD Clinical Practice Consensus Guidelines 2006?2007 The diagnosis and management of monogenic diabetes in children

Cited by 120 publications

References 61 publications

Response to oral gliclazide in a pre-pubertal child with hepatic nuclear factor-1 alpha maturity onset diabetes of the young

Response to oral gliclazide in a pre-pubertal child with hepatic nuclear factor-1 alpha maturity onset diabetes of the young

Insulin gene mutations as a cause of permanent neonatal diabetes

Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function

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