Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Diabetes Obes Metab. 2018 Nov;20(11):2685-2689. doi: 10.1111/dom.13439. Epub 2018 Jul 12.
We investigated the short-term effects of dapagliflozin as adjunct to insulin on insulin sensitivity, postprandial glucose excursions and ketone body production in type 1 diabetes mellitus (T1DM). A total of seven male patients completed the randomized, double-blind, placebo-controlled cross-over trial, receiving 10 mg of dapagliflozin daily for 3 days, followed by placebo, or the reverse. At Day 3, hyperinsulinaemic, euglycaemic clamps and oral glucose tolerance test clamps with repeated blood sampling were performed. Required glucose infusion and blood glucose excursions did not differ significantly between dapagliflozin treatment and placebo (P = 0.491; P = 0.342). Prior to oral glucose, total ketone bodies showed a higher trend following dapagliflozin treatment (P = 0.051). Following oral glucose, total ketone bodies decreased while concentrations of total GLP-1 were higher following dapagliflozin (P = 0.009). Non-esterified free fatty acids did not differ between dapagliflozin treatment and placebo and ketonuria was absent under both conditions. In T1DM, short-term addition of dapagliflozin to insulin influenced neither postprandial glucose excursions nor insulin sensitivity. Following oral glucose, total ketone bodies decreased in parallel with an increase in GLP-1 concentrations, which were higher under dapagliflozin treatment as compared with placebo.
我们研究了达格列净作为胰岛素辅助治疗对 1 型糖尿病患者胰岛素敏感性、餐后血糖波动和酮体生成的短期影响。共有 7 名男性患者完成了这项随机、双盲、安慰剂对照交叉试验，每天接受 10 毫克达格列净治疗 3 天，然后是安慰剂或相反的治疗。在第 3 天，进行了高胰岛素-正葡萄糖钳夹和口服葡萄糖耐量试验钳夹，并重复采血。达格列净治疗和安慰剂治疗之间，所需的葡萄糖输注量和血糖波动没有显著差异（P=0.491；P=0.342）。在口服葡萄糖之前，总酮体在达格列净治疗后呈现出更高的趋势（P=0.051）。口服葡萄糖后，总酮体减少，而总 GLP-1 浓度升高（P=0.009）。达格列净治疗和安慰剂治疗之间的非酯化游离脂肪酸没有差异，两种情况下均未出现酮尿症。在 1 型糖尿病患者中，短期添加达格列净对胰岛素既不影响餐后血糖波动，也不影响胰岛素敏感性。口服葡萄糖后，总酮体与 GLP-1 浓度的增加平行下降，与安慰剂相比，达格列净治疗时的 GLP-1 浓度更高。
