Diabetes Care. 2018 Aug;41(8):1726-1731. doi: 10.2337/dc18-0384. Epub 2018 May 29.
To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α () found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3.
We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers). Response to glipizide (one 2.5-5.0-mg dose), metformin (four 500-mg doses), and an oral glucose challenge was evaluated using a previously validated protocol. Glucose and insulin levels and their areas under the curve (AUCs) were compared between groups.
Carriers of the p.E508K variant had a lower maximum insulin peak during the glipizide challenge as compared with noncarriers with diabetes ( < 0.05). Also, carriers had a lower insulin response after the oral glucose challenge. Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes ( < 0.05). A similar but nonsignificant trend was seen in participants without type 2 diabetes.
Carriers of variant p.E508K in have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.
评估在墨西哥人群中发现的青年起病的成年型糖尿病（MODY）基因肝细胞核因子-1α（）中特有的种族变异（p.E508K）是否与磺酰脲类药物的更高敏感性相关，这在 MODY3 患者中已有记载。
我们招募了 96 名参与者（46 名变异携带者和 50 名年龄和性别匹配的非携带者）。使用先前验证的方案评估格列吡嗪（一次 2.5-5.0mg 剂量）、二甲双胍（四次 500mg 剂量）和口服葡萄糖挑战的反应。比较两组之间的葡萄糖和胰岛素水平及其曲线下面积（AUCs）。
与糖尿病非携带者相比，p.E508K 变异携带者在格列吡嗪挑战期间的最大胰岛素峰值较低（<0.05）。此外，携带者在口服葡萄糖挑战后的胰岛素反应较低。在二甲双胍存在的情况下进行口服葡萄糖耐量试验后，糖尿病变异携带者的最大胰岛素峰值以及总胰岛素和增量胰岛素 AUC 值均低于糖尿病非携带者（<0.05）。在没有 2 型糖尿病的参与者中也观察到类似但无统计学意义的趋势。
携带 p.E508K 变异的个体的胰岛素反应降低，而不是像 MODY3 患者那样对磺酰脲类药物的敏感性增加。
