Koceva Andrijana, Kravos Tramšek Nika Aleksandra
Department of Endocrinology and Diabetology, University Medical Center Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia.
Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia.
J Pers Med. 2024 Jun 21;14(7):665. doi: 10.3390/jpm14070665.
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are highly selective, effective, and generally well-tolerated antihyperglycemic agents targeting the SGLT-2 transmembrane protein. Despite being primarily registered for diabetes treatment, due to their cardiorenal protective properties, SGLT-2 inhibitors caused a paradigm shift in the treatment of other diseases on the cardiorenal spectrum, becoming a fundamental part of heart failure and chronic kidney disease management. With their rapidly increasing use, there are also increased reports of a rare, often under-recognised and potentially deadly side effect, SGLT-2-inhibitor-induced euglycemic diabetic ketoacidosis (EDKA). The primary pathophysiological process behind its multifactorial aetiology comprises glucosuria and osmotic diuresis, which produce a significant carbohydrate deficit, leading to an increase in the glucagon-insulin ratio, thus resulting in accelerated ketogenesis. Although EDKA has a similar clinical presentation as diabetic ketoacidosis (DKA), the absence of the high glucose levels typically expected for DKA and the presence of urine ketone reabsorption contribute to a significant delay in its recognition and timely diagnosis. Given the broad use of SGLT-2 inhibitors, increased awareness, early recognition, and prompt identification of precipitating factors are essential. In this narrative review, we comprehensively explore the pathophysiological mechanisms of SGLT-2-inhibitor-induced EDKA, analyse its clinical manifestation, and identify the most common triggers for its development. We also discuss EDKA management and preventive strategies.
钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂是一类高度选择性、有效且耐受性良好的抗高血糖药物，作用于SGLT-2跨膜蛋白。尽管SGLT-2抑制剂主要获批用于糖尿病治疗，但因其具有心脏和肾脏保护特性，在心脏和肾脏疾病谱的其他疾病治疗中引发了范式转变，成为心力衰竭和慢性肾脏病管理的重要组成部分。随着其使用的迅速增加，一种罕见、常未被充分认识且可能致命的副作用——SGLT-2抑制剂诱导的正常血糖性糖尿病酮症酸中毒（EDKA）的报告也日益增多。其多因素病因背后的主要病理生理过程包括糖尿和渗透性利尿，这会导致显著的碳水化合物缺乏，进而使胰高血糖素-胰岛素比值升高，从而加速酮体生成。尽管EDKA的临床表现与糖尿病酮症酸中毒（DKA）相似，但缺乏DKA通常预期的高血糖水平以及存在尿酮体重吸收，导致其识别和及时诊断出现显著延迟。鉴于SGLT-2抑制剂的广泛使用，提高认识、早期识别并迅速确定诱发因素至关重要。在这篇叙述性综述中，我们全面探讨了SGLT-2抑制剂诱导的EDKA的病理生理机制，分析其临床表现，并确定其发生发展最常见的触发因素。我们还讨论了EDKA的管理和预防策略。
