Veterans Affairs Medical Center, San Diego, CA, USA.
Department of Medicine, University of California at San Diego, San Diego School of Medicine, San Diego, USA.
Curr Diab Rep. 2020 Nov 23;20(12):74. doi: 10.1007/s11892-020-01359-z.
The micro/macrovascular complications of diabetes cause considerable morbidity and premature mortality. The SGLT2 inhibitors are the first diabetes medications with significant benefits on microvascular disease (nephropathy) and macrovascular cardiovascular disease. In this review, we evaluate one of the potential mechanisms for these cardiorenal benefits-the production of ketones, their benefits, and risks.
In recent cardiovascular outcome trials (CVOTs), the SGLT2 inhibitors demonstrated significant cardiorenal benefits and they are now approved to reduce CV events/death, heart failure hospitalization, and progression to end-stage renal disease. Glucosuria induced by the SGLT2 inhibitors leads to increased ketone production. Ketones are an efficient fuel source and can improve myocardial and renal function. Further, the ketone body beta-hydroxybutyrate exhibits anti-inflammatory/anti-oxidative actions, which favorably impact myocardial and renal remodeling/fibrosis. Uncontrolled ketogenesis leads to ketoacidosis, especially during conditions of acute illness and excessive insulin dose reductions. The SGLT2 inhibitors have demonstrated significant cardiorenal benefits in large CVOTs. Studies are in progress to elucidate whether SGLT2 inhibitor-induced low-grade hyperketonemia contributes to these benefits.
糖尿病的微血管和大血管并发症导致相当大的发病率和过早死亡率。SGLT2 抑制剂是第一批对微血管疾病（肾病）和大血管心血管疾病有显著益处的糖尿病药物。在这篇综述中，我们评估了这些心肾益处的一个潜在机制——酮的产生、它们的益处和风险。
在最近的心血管结局试验（CVOT）中，SGLT2 抑制剂显示出显著的心肾益处，现在已被批准用于减少心血管事件/死亡、心力衰竭住院和进展为终末期肾病。SGLT2 抑制剂引起的葡萄糖尿导致酮的产生增加。酮是一种有效的燃料来源，可以改善心肌和肾功能。此外，酮体β-羟丁酸具有抗炎/抗氧化作用，有利于心肌和肾脏重塑/纤维化。失控的酮生成会导致酮症酸中毒，尤其是在急性疾病和胰岛素剂量过度减少的情况下。SGLT2 抑制剂在大型 CVOT 中显示出显著的心肾益处。目前正在进行研究，以阐明 SGLT2 抑制剂诱导的轻度高酮血症是否有助于这些益处。
