Document Detail


The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes.
MedLine Citation:
PMID:  16595597     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Several studies suggest that genetic factors may play a role in the different responses to antidiabetic therapy; however, conclusive evidence is still lacking.
OBJECTIVE: The objective of the study was to investigate whether diabetic patients carrying the E23K variant in KCNJ11 are at increased risk for secondary sulfonylurea failure.
DESIGN: Secondary sulfonylurea failure was defined as fasting plasma glucose greater than 300 mg/dl despite sulfonylurea-metformin combined therapy and appropriate diet, in the absence of other conditions causing hyperglycemia.
SETTING: The study was conducted in an ambulatory care facility.
PATIENTS: A total of 525 Caucasian type 2 diabetic patients were enrolled in the study.
INTERVENTION: Sulfonylurea treatment was followed by sulfonylurea-metformin combined therapy and then insulin treatment.
MAIN OUTCOME MEASURE: Secondary failure was the main outcome measure.
RESULTS: Of the diabetic patients enrolled in the study, 38.5% were E23E homozygous, 51.4% were E23K heterozygous, and 10.1% were K23K homozygous. The frequency of carriers of the K allele was 58 and 66.8% among patients treated with oral therapy or secondary sulfonylurea failure, respectively (odds ratio, 1.45; 95% confidence interval, 1.01-2.09; P = 0.04). Adjustment for age, gender, fasting glycemia, glycosylated hemoglobin, age at diagnosis, and duration of diabetes in a logistic regression analysis did not change this association (odds ratio, 1.69; 95% confidence interval, 1.02-2.78; P = 0.04). Islets isolated from carriers of the K allele showed no differences in glucose-stimulated insulin secretion and a tendency toward reduced response upon glibenclamide stimulation (P = 0.09). After 24-h exposure to high (16.7 mmol/liter) glucose concentration, impairment of glibenclamide-induced insulin release was significantly (P = 0.01) worse with the E23K variant.
CONCLUSIONS: These data suggest that the E23K variant in KCNJ11 may influence the variability in the response of patients to sulfonylureas, thus representing an example of pharmacogenetics in type 2 diabetes.
Authors:
Giorgio Sesti; Emanuela Laratta; Marina Cardellini; Francesco Andreozzi; Silvia Del Guerra; Concetta Irace; Agostino Gnasso; Maria Grupillo; Renato Lauro; Marta Letizia Hribal; Francesco Perticone; Piero Marchetti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-04-04
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  91     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-07     Completed Date:  2006-06-29     Revised Date:  2014-07-29    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2334-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Diabetes Mellitus, Type 2 / drug therapy*,  genetics*
Female
Genetic Variation
Humans
Hypoglycemic Agents / therapeutic use*
Male
Middle Aged
Potassium Channels, Inwardly Rectifying / genetics*
Sulfonylurea Compounds / therapeutic use*
Treatment Failure
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Kir6.2 channel; 0/Potassium Channels, Inwardly Rectifying; 0/Sulfonylurea Compounds

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


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