Petersen Max C, Jones Kai E, Markov Alexander M, Salam Maamoun, Krutilova Petra, McKee Alexis M, Bohnert Kathryn L, Adamson Samantha E, McGill Janet B
Division of Endocrinology, Metabolism, & Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA.
Diabetes Obes Metab. 2025 Jun;27(6):3124-3131. doi: 10.1111/dom.16324. Epub 2025 Mar 13.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors increase ketoacidosis risk, limiting their use in type 1 diabetes. To better understand the pathophysiology of SGLT2 inhibitor-mediated ketoacidosis, we measured blood glucose, capillary blood and plasma β-hydroxybutyrate (BOHB) and breath acetone (BrACE) during supervised insulin withdrawal in adults with type 1 diabetes with and without dapagliflozin treatment.
Twenty adults with type 1 diabetes underwent supervised insulin withdrawal twice in a randomized crossover design: during usual care and after treatment with dapagliflozin (10 mg daily for 2 weeks plus the test day). After insulin withdrawal, capillary blood glucose, BOHB and BrACE measurements were obtained at least hourly until stopping rules were met (>8 h elapsed, symptoms of ketosis, glucose >400 mg/dL, BOHB >4 mmol/L or participant request).
The peak BOHB and BrACE values achieved during supervised insulin withdrawal were both greater with dapagliflozin than with usual care. Throughout the insulin withdrawal study, dapagliflozin treatment was associated with significantly greater BOHB and BrACE concentrations. The proportions of participants reaching BOHB >1.5 mmol/L and >2.5 mmol/L during supervised insulin withdrawal were greater in the dapagliflozin arm. Blood glucose reached a lower peak in the dapagliflozin arm.
In adults with type 1 diabetes undergoing supervised insulin withdrawal, dapagliflozin treatment compared to usual care was associated with greater blood and breath ketone concentrations in the absence of significant hyperglycaemia.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂会增加酮症酸中毒风险，限制了其在1型糖尿病中的应用。为了更好地理解SGLT2抑制剂介导的酮症酸中毒的病理生理学，我们在有或没有达格列净治疗的1型糖尿病成人患者进行监督性胰岛素撤药期间，测量了血糖、毛细血管血和血浆β-羟基丁酸（BOHB）以及呼气丙酮（BrACE）。
20名1型糖尿病成人患者采用随机交叉设计进行了两次监督性胰岛素撤药：一次是在常规护理期间，另一次是在接受达格列净治疗后（每日10毫克，持续2周加测试日）。胰岛素撤药后，至少每小时测量一次毛细血管血糖、BOHB和BrACE，直至满足停止规则（经过>8小时、出现酮症症状、血糖>400mg/dL、BOHB>4mmol/L或参与者要求）。
在监督性胰岛素撤药期间，达格列净组达到的BOHB和BrACE峰值均高于常规护理组。在整个胰岛素撤药研究中，达格列净治疗与显著更高的BOHB和BrACE浓度相关。在监督性胰岛素撤药期间，达格列净组中BOHB>1.5mmol/L和>2.5mmol/L的参与者比例更高。达格列净组的血糖达到的峰值更低。
在接受监督性胰岛素撤药的1型糖尿病成人患者中，与常规护理相比，达格列净治疗在无明显高血糖的情况下与更高的血液和呼气酮浓度相关。
