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Aim: The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exonl6-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. Methods: A total of 100 Chinese patients with newly diag- nosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimu- lation 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 Ale (HbAlc) values (or both) after the 24 week repaglinide treatment. Results: Both baseline HbAlc and the decrease of HbAlc 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 signifi- cantly 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 exon 16-3 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 sensi- tivity than the T/C and T/T genotypes.