Falco Luigi, Di Lorenzo Emilio, Masarone Daniele
Department of Cardiology, AORN dei Colli Monaldi Hospital, Naples 80131, Italy.
World J Cardiol. 2025 Mar 26;17(3):102893. doi: 10.4330/wjc.v17.i3.102893.
Heart failure (HF), which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications, has been overlooked for long time in diabetic patients, despite its increasing prevalence and mortality. As originally stated in the Framingham studies, diabetes is associated with an increased risk of HF. Subsequent studies not only corroborated these findings but also identified HF as the most frequent first onset of cardiovascular involvement. The paramount role of proper management of common modifiable risk factors such as hypertension, obesity, dyslipidemia and smoking, became rapidly clear. Conversely, the impact of intensive glycemic control was more contentious. A large meta-analysis of randomized controlled trials reported a lack of effect of strict glycemic control as compared to standard care on HF-related outcomes. The considerable heterogeneity of the effect estimate and the higher risk conferred by thiazolidinediones suggested that mechanism of action of antidiabetic drugs played a key role. Furthermore, the safety concerns of pioglitazone led Food and Drug Administration to release a guidance for drug manufacturers stating that cardiovascular risk should be comprehensively evaluated during drug development. Surprisingly, in just a few years, large cardiovascular outcome trials established the beneficial cardiovascular effects of sodium-glucose cotransporter 2 inhibitors. These effects were consistent regardless diabetes and ejection fraction. Therefore, scientific community started to question the glucose-lowering and diuretic properties of sodium-glucose cotransporter 2 inhibitors as the unique mechanisms for improved outcomes. A plenty of preclinical and clinical studies identified several mechanisms besides glucose-lowering effects. However, these mechanistic studies focused on animal models and patients with established HF. If the same mechanisms account for beneficial effects in patients at risk for or with pre-HF is unknown. Grubić Rotkvić published an interesting work adding data in early stages HF.
心力衰竭（HF）不属于糖尿病并发症的传统大血管或微血管分类范畴，尽管其患病率和死亡率不断上升，但在糖尿病患者中长期被忽视。正如弗明汉姆研究最初所述，糖尿病与HF风险增加有关。随后的研究不仅证实了这些发现，还将HF确定为心血管受累最常见的首发情况。对高血压、肥胖、血脂异常和吸烟等常见可改变风险因素进行适当管理的至关重要作用很快就显现出来。相反，强化血糖控制的影响则更具争议性。一项对随机对照试验的大型荟萃分析报告称，与标准治疗相比，严格血糖控制对HF相关结局没有效果。效应估计的显著异质性以及噻唑烷二酮类药物带来的更高风险表明，抗糖尿病药物的作用机制起了关键作用。此外，吡格列酮的安全性问题导致美国食品药品监督管理局向药品制造商发布了一份指南，指出在药物研发过程中应全面评估心血管风险。令人惊讶的是，在短短几年内，大型心血管结局试验证实了钠-葡萄糖协同转运蛋白2抑制剂对心血管有益。无论糖尿病和射血分数如何，这些效果都是一致的。因此，科学界开始质疑钠-葡萄糖协同转运蛋白2抑制剂的降糖和利尿特性是否是改善结局的唯一机制。大量临床前和临床研究确定了除降糖作用外的几种机制。然而，这些机制研究集中在动物模型和已确诊HF的患者身上。对于这些机制是否也能解释对有HF风险或处于HF前期患者的有益作用尚不清楚。格鲁比奇·罗特克维奇发表了一项有趣的研究，为HF早期阶段增加了数据。
