Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes. 2014 Apr;63(4):1315-25. doi: 10.2337/db13-1454. Epub 2013 Dec 18.
Patients with loss-of-function mutations in KCNQ1 have KCNQ1 long QT syndrome (LQTS). KCNQ1 encodes a voltage-gated K(+) channel located in both cardiomyocytes and pancreatic β-cells. Inhibition of KCNQ1 in β-cells increases insulin secretion. Therefore KCNQ1 LQTS patients may exhibit increased insulin secretion. Fourteen patients, from six families, diagnosed with KCNQ1 LQTS were individually matched to two randomly chosen BMI-, age-, and sex-matched control participants and underwent an oral glucose tolerance test (OGTT), a hypoglycemia questionnaire, and continuous glucose monitoring. KCNQ1 mutation carriers showed increased insulin release (area under the curve 45.6 ± 6.3 vs. 26.0 ± 2.8 min ⋅ nmol/L insulin) and β-cell glucose sensitivity and had lower levels of plasma glucose and serum potassium upon oral glucose stimulation and increased hypoglycemic symptoms. Prolonged OGTT in four available patients and matched control subjects revealed hypoglycemia in carriers after 210 min (range 1.4-3.6 vs. 4.1-5.3 mmol/L glucose), and 24-h glucose profiles showed that the patients spent 77 ± 18 min per 24 h in hypoglycemic states (<3.9 mmol/L glucose) with 36 ± 10 min (<2.8 mmol/L glucose) vs. 0 min (<3.9 mmol/L glucose) for the control participants. The phenotype of patients with KCNQ1 LQTS, caused by mutations in KCNQ1, includes, besides long QT, hyperinsulinemia, clinically relevant symptomatic reactive hypoglycemia, and low potassium after an oral glucose challenge, suggesting that KCNQ1 mutations may explain some cases of "essential" reactive hypoglycemia.
患有 KCNQ1 功能丧失突变的患者患有 KCNQ1 长 QT 综合征 (LQTS)。KCNQ1 编码一种位于心肌细胞和胰岛 β 细胞中的电压门控 K(+)通道。β 细胞中 KCNQ1 的抑制会增加胰岛素分泌。因此，KCNQ1 LQTS 患者可能表现出胰岛素分泌增加。从六个家族中诊断出 14 名患有 KCNQ1 LQTS 的患者，与两名随机选择的 BMI、年龄和性别匹配的对照参与者进行个体匹配，并进行口服葡萄糖耐量试验 (OGTT)、低血糖问卷和连续血糖监测。KCNQ1 突变携带者显示出胰岛素释放增加（曲线下面积 45.6 ± 6.3 与 26.0 ± 2.8 min ⋅ nmol/L 胰岛素）和 β 细胞葡萄糖敏感性，并且在口服葡萄糖刺激时血糖和血清钾水平降低，低血糖症状增加。在四名可提供的患者和匹配的对照中进行的延长 OGTT 显示，携带者在 210 分钟后出现低血糖（范围 1.4-3.6 与 4.1-5.3 mmol/L 葡萄糖），24 小时血糖谱显示患者在 24 小时中有 77 ± 18 分钟处于低血糖状态（<3.9 mmol/L 葡萄糖），而对照参与者的 36 ± 10 分钟（<2.8 mmol/L 葡萄糖）和 0 分钟（<3.9 mmol/L 葡萄糖）没有低血糖。由 KCNQ1 突变引起的 KCNQ1 LQTS 患者的表型除长 QT 外，还包括高胰岛素血症、临床上相关的症状性反应性低血糖和口服葡萄糖后低钾血症，这表明 KCNQ1 突变可能解释了一些“特发性”反应性低血糖病例。
