Abstract：
OBJECTIVE: Clinical trials showed the efficacy of sodium-glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat-AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium-glucose cotransporter 2 inhibitor, ipragliflozin.
METHODS: Adults with T1D (n = 25) took 50-mg open-labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed-meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C-peptide, glucagon and β-hydroxybutyrate.
RESULTS: The area under the curve from fasting (0 min) to 120 min (AUC0-120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial β-hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0-120min) from baseline to 12 weeks were significantly correlated with those in β-hydroxybutyrate levels.
CONCLUSIONS: Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied.
METHODS: Adults with T1D (n = 25) took 50-mg open-labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed-meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C-peptide, glucagon and β-hydroxybutyrate.
RESULTS: The area under the curve from fasting (0 min) to 120 min (AUC0-120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial β-hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0-120min) from baseline to 12 weeks were significantly correlated with those in β-hydroxybutyrate levels.
CONCLUSIONS: Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied.
摘要：
目的：临床试验表明，钠-葡萄糖协同转运蛋白2抑制剂对1型糖尿病（T1D）的疗效显著降低体重和血糖变异性，但通过胰高血糖素分泌升高引起的酮症酸中毒易感性升高是一个潜在的问题.Suglat-AID评估了用钠-葡萄糖协同转运蛋白2抑制剂T1D治疗前后胰高血糖素反应及其与血糖控制和生酮的关系，Ipragragliflozin.
方法：患有T1D的成年人（n=25）每天服用50-mg开放标记的伊格列净作为胰岛素的辅助药物。收集包括连续葡萄糖监测在内的实验室/临床数据,直至伊曲列净开始后12周。参与者进行了两次混合膳食耐量测试（MMTT）[之前（第一次MMTT）和伊格列净治疗后12周（第二次MMTT）]以评估葡萄糖的反应，C-肽，胰高血糖素和β-羟基丁酸。
结果：第二次MMTT中胰高血糖素从禁食（0分钟）到120分钟（AUC0-120分钟）的曲线下面积比第一次MMTT显着增加了14％。与第一次MMTT相比，第二次MMTT中的空腹和餐后β-羟丁酸水平显着升高。在第一次MMTT中观察到的餐后胰高血糖素分泌与葡萄糖波动之间的正相关在第二次MMTT中消失，但空腹胰高血糖素与低于范围的时间(葡萄糖，<3.9mmol/L）出现在第二个MMTT中。从基线到12周，胰高血糖素水平（空腹和AUC0-120min）的百分比变化与β-羟基丁酸水平的变化显着相关。
结论：伊曲列净治疗T1D可增加餐后胰高血糖素分泌，不会加剧餐后高血糖，但可能会预防低血糖，导致血糖变异性降低。当没有提供足够的胰岛素时，胰高血糖素分泌的增加可能会加速酮生成。
方法：患有T1D的成年人（n=25）每天服用50-mg开放标记的伊格列净作为胰岛素的辅助药物。收集包括连续葡萄糖监测在内的实验室/临床数据,直至伊曲列净开始后12周。参与者进行了两次混合膳食耐量测试（MMTT）[之前（第一次MMTT）和伊格列净治疗后12周（第二次MMTT）]以评估葡萄糖的反应，C-肽，胰高血糖素和β-羟基丁酸。
结果：第二次MMTT中胰高血糖素从禁食（0分钟）到120分钟（AUC0-120分钟）的曲线下面积比第一次MMTT显着增加了14％。与第一次MMTT相比，第二次MMTT中的空腹和餐后β-羟丁酸水平显着升高。在第一次MMTT中观察到的餐后胰高血糖素分泌与葡萄糖波动之间的正相关在第二次MMTT中消失，但空腹胰高血糖素与低于范围的时间(葡萄糖，<3.9mmol/L）出现在第二个MMTT中。从基线到12周，胰高血糖素水平（空腹和AUC0-120min）的百分比变化与β-羟基丁酸水平的变化显着相关。
结论：伊曲列净治疗T1D可增加餐后胰高血糖素分泌，不会加剧餐后高血糖，但可能会预防低血糖，导致血糖变异性降低。当没有提供足够的胰岛素时，胰高血糖素分泌的增加可能会加速酮生成。
