Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes.

Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Research Abstract Details 

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Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Abstract Text:

Monogenic diabetes resulting from mutations that primarily reduce beta-cell function accounts for 1-2% of diabetes cases, although it is often misdiagnosed as either type 1 or type 2 diabetes. Knowledge of the genetic etiology of diabetes enables more-appropriate treatment, better prediction of disease progression, screening of family members and genetic counseling. We propose that the old clinical classifications of maturity-onset diabetes of the young and neonatal diabetes are obsolete and that specific genetic etiologies should be sought in four broad clinical situations because of their specific treatment implications. Firstly, diabetes diagnosed before 6 months of age frequently results from mutation of genes that encode Kir6.2 (ATP-sensitive inward rectifier potassium channel) or sulfonylurea receptor 1 subunits of an ATP-sensitive potassium channel, and improved glycemic control can be achieved by treatment with high-dose sulfonylureas rather than insulin. Secondly, patients with stable, mild fasting hyperglycemia detected particularly when they are young could have a glucokinase mutation and might not require specific treatment. Thirdly, individuals with familial, young-onset diabetes that does not fit with either type 1 or type 2 diabetes might have mutations in the transcription factors HNF-1alpha (hepatocyte nuclear factor 1-alpha) or HNF-4alpha, and can be treated with low-dose sulfonylureas. Finally, extrapancreatic features, such as renal disease (caused by mutations in HNF-1beta) or deafness (caused by a mitochondrial m.3243A>G mutation), usually require early treatment with insulin.

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Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature clinical practice. Endocrinology & metaboli

VOLUME: 4

Page Numbers: 200-13

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ISSN: 1745-8374

DAY: 26

MONTH: 02

YEAR: 2008

Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes.

AFFILIATION: Peninsula Medical School, Exeter, UK.

Country: England

AGENCY: United Kingdom Wellcome T

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MEDLINETA: Nat Clin Pract Endocrinol Meta

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