Abstract
Aim:
The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16–3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes.
Methods:
A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment.
Results:
Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P =0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P =0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16–3 C/C versus the T/C and T/T genotypes (P =0.0372 and 0.0274, respectively).
Conclusion:
The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16–3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.
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This work was funded by the Key Project from Science and Technology Commission of Shanghai Municipality, China (No 01DZ002 [1]), the National 973 Program (No 2006CB503901), and by the Program for Shanghai Outstanding Medical Academic Leader (No LJ06010).
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He, Yy., Zhang, R., Shao, Xy. et al. Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients. Acta Pharmacol Sin 29, 983–989 (2008). https://doi.org/10.1111/j.1745-7254.2008.00840.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00840.x
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