Pfützner A, Klonoff D, Heinemann L, Ejskjaer N, Pickup J
Pfützner Science & Health Institute, Mainz, UK.
Mills Peninsula Healthcare Services, San Mateo, USA.
Endocrine. 2017 Apr;56(1):212-216. doi: 10.1007/s12020-017-1264-y. Epub 2017 Mar 17.
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials. However, sodium-glucose cotransporter2 inhibitors increase the risk of ketosis by increasing glucagon secretion in the pancreas and decreasing the renal excretion of 3-hydroxybutyrate and acetoacetate. When used in addition to insulin, any insulin dose reduction required to avoid hypoglycemia may lead to insufficient suppression of lipolysis and ketogenesis. sodium-glucose cotransporter2 inhibitor-induced loss of urinary glucose encourages euglycemia. Normo-glycemic or near-normoglycemic diabetic ketoacidosis represents a major threat to the health and well-being of a patient, because it may occur undetected and without any indicative hyperglycemia. In consequence, patients on sodium-glucose cotransporter2 inhibitors are recommended to perform regular blood ketone tests since they are not alerted to incipient diabetic ketoacidosis by glucose testing alone. This option is offered by several blood glucose meters that can also measure ketones with a separate ketone strip or in one case by an automatic parallel ketone assessment from the same strip. The need for extra testing and the associated costs may be a barrier to patient acceptance of this risk mitigation procedure. However, patients who are at risk for euglycemic diabetic ketoacidosis when being treated with sodium-glucose cotransporter2 inhibitors should be specially advised to monitor blood ketone levels on a regular basis.
糖尿病酮症酸中毒是一种不常见但危及生命的糖尿病急性并发症,主要影响1型糖尿病患者、儿童和孕妇,其中酮症通常与显著的高血糖相关。最近,在常规实践中,越来越多接受钠-葡萄糖协同转运蛋白2抑制剂治疗的2型糖尿病患者出现了正常血糖性糖尿病酮症酸中毒的病例报告。这类药物存在轻微但不可忽视的糖尿病酮症酸中毒风险,这在随机临床试验中并未观察到。然而,钠-葡萄糖协同转运蛋白2抑制剂通过增加胰腺中胰高血糖素的分泌以及减少3-羟基丁酸和乙酰乙酸的肾排泄,增加了酮症风险。当与胰岛素联合使用时,为避免低血糖而需要减少的任何胰岛素剂量可能导致对脂肪分解和酮生成的抑制不足。钠-葡萄糖协同转运蛋白2抑制剂导致的尿糖丢失促使血糖正常。正常血糖或接近正常血糖的糖尿病酮症酸中毒对患者的健康和福祉构成重大威胁,因为它可能在未被察觉且没有任何指示性高血糖的情况下发生。因此,建议使用钠-葡萄糖协同转运蛋白2抑制剂的患者定期进行血酮检测,因为仅通过血糖检测无法提醒他们早期糖尿病酮症酸中毒的发生。几种血糖仪提供了这种选择,它们可以使用单独的酮试纸条测量酮体,或者在一种情况下通过同一条试纸自动并行进行酮体评估。额外检测的需求和相关费用可能成为患者接受这种风险缓解措施的障碍。然而,对于在使用钠-葡萄糖协同转运蛋白-2抑制剂治疗时存在正常血糖性糖尿病酮症酸中毒风险的患者,应特别建议他们定期监测血酮水平。