Document Detail

Permanent neonatal diabetes mellitus caused by a novel homozygous (T168A) glucokinase (GCK) mutation: initial response to oral sulphonylurea therapy.
MedLine Citation:
PMID:  18571549     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To evaluate the clinical response to sulphonylurea treatment in a child with a homozygous T168A GCK (glucokinase) mutation, causing permanent neonatal diabetes mellitus (PNDM). STUDY DESIGN: Oral glibenclamide was given for 3 months. Pancreatic beta cell function was assessed by a glucagon stimulation test. Mutant and wild-type (WT) GCK were characterized. RESULTS: Sulphonylurea treatment resulted in a 12-fold increase in basal and stimulated C-peptide levels. HbA1c levels were reduced from 9.4% to 8.1% on a reduced insulin dose (0.85 to 0.60 U/kg/day). Mutant T168A-GST-GCK showed reduced kinetic activity (0.02 fold) compared to WT. CONCLUSIONS: Sulphonylureas can close the adenosine triphosphate (ATP)-sensitive potassium channel and elicit insulin secretion, but the ATP generated from metabolism is insufficient to fully restore insulin secretory capacity. Nonetheless, sulphonylurea treatment should be tried in patients with GCK-PNDM, particularly those with mutations resulting in less severe kinetic defects, in whom improved glycemic control may be obtained with lower doses of insulin.
Doga Turkkahraman; Iffet Bircan; Nicholas D Tribble; Sema Akçurin; Sian Ellard; Anna L Gloyn
Related Documents :
16055439 - Sterol regulatory element-binding proteins activate insulin gene promoter directly and ...
2805359 - Alterations of purine metabolism in mononuclear cells of individuals at risk of develop...
3520719 - Dopamine-beta-hydroxylase activity in plasma, spleen and adrenal gland of streptozotoci...
11151759 - Assessment of insulin sensitivity and beta-cell function from measurements in the fasti...
2422249 - Detection of insulin synthesis in mammalian anterior pituitary cells by immunohistochem...
16241869 - Nanoporous alumina capsules for cellular macroencapsulation: transport and biocompatibi...
16219009 - Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of m...
24381649 - Sense of coherence in people with and without type 2 diabetes mellitus: an observationa...
2027059 - Manifestations of insulin-dependent diabetes mellitus in the periodontium of young braz...
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-06
Journal Detail:
Title:  The Journal of pediatrics     Volume:  153     ISSN:  1097-6833     ISO Abbreviation:  J. Pediatr.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-23     Completed Date:  2008-07-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375410     Medline TA:  J Pediatr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  122-6     Citation Subset:  AIM; IM    
From the Department of Pediatric Endocrinology, Akdeniz University Hospital, Antalya, Turkey.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Administration, Oral
Diabetes Mellitus / genetics*
Family Health
Glucokinase / chemistry,  genetics*
Glyburide / therapeutic use
Infant, Newborn
Insulin / therapeutic use
Mutation, Missense
Protein Conformation
Sulfonylurea Compounds / administration & dosage,  therapeutic use*
Treatment Outcome
Reg. No./Substance:
0/Sulfonylurea Compounds; 10238-21-8/Glyburide; 11061-68-0/Insulin; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Resistance to intravenous immunoglobulin in children with Kawasaki disease.
Next Document:  Pattern and course of neurodegeneration in Langerhans cell histiocytosis.