Li Qing, Chen Miao, Zhang Rong, Jiang Feng, Wang Jie, Zhou Jian, Bao Yuqian, Hu Cheng, Jia Weiping
Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center of Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
Clin Exp Pharmacol Physiol. 2014 Oct;41(10):748-54. doi: 10.1111/1440-1681.12280.
The aim of the present study was to investigate the effect of the E23K variant of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene on gliclazide modified release (MR) treatment in newly diagnosed patients with type 2 diabetes mellitus (T2DM). A total of 108 diabetic patients with no history of antidiabetic medication was treated with gliclazide MR for 16 weeks and underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood glucose and lower serum insulin levels after oral glucose administration than patients with the EE and EK genotypes (P < 0.05 for all). During treatment, individuals with the KK genotype had lower fasting glucose levels and were more likely to attain the target fasting glucose level (Plog rank = 0.028) than E allele carriers. Patients with the KK genotype had larger augmentations in changes (Δ) in acute insulin response (P = 0.049) and Δ body mass index (P = 0.003). Moreover, patients with the EK genotype had a lower variance in changes in fasting insulin levels (P = 0.049) and homeostasis model assessment of β-cell function (P = 0.021) than those with the KK genotype. The findings of the present study suggest that the KCNJ11 E23K variant is associated with a greater effect of sulphonylurea treatment in newly diagnosed Chinese patients with T2DM.
本研究旨在探讨内向整流钾通道亚家族J成员11（KCNJ11）基因的E23K变异对新诊断的2型糖尿病（T2DM）患者格列齐特缓释（MR）治疗效果的影响。共有108例无抗糖尿病药物治疗史的糖尿病患者接受格列齐特MR治疗16周，并在第2、4、8、12和16周进行随访。所有患者均进行KCNJ11 E23K（rs5219）基因分型。在基线时，与EE和EK基因型患者相比，KK基因型患者口服葡萄糖后血糖更高，血清胰岛素水平更低（所有P<0.05）。在治疗期间，与E等位基因携带者相比，KK基因型个体空腹血糖水平更低，更有可能达到空腹血糖目标水平（Plog rank = 0.028）。KK基因型患者急性胰岛素反应变化（Δ）（P = 0.049）和Δ体重指数（P = 0.003）的增加幅度更大。此外，与KK基因型患者相比，EK基因型患者空腹胰岛素水平变化（P = 0.049）和β细胞功能稳态模型评估（P = 0.021）的方差更低。本研究结果表明，KCNJ11 E23K变异与新诊断的中国T2DM患者磺脲类药物治疗效果更佳有关。
