SGLT-2抑制剂使2型糖尿病患者获益机制研究进展

钠-葡萄糖共转运蛋白-2抑制剂（SGLT-2is）是治疗2型糖尿病（T2DM）的一种降糖药物,其通过作用于肾脏发挥降糖作用。目前相关指南已经提出将SGLT-2is用于伴有心力衰竭或慢性肾脏病的T2DM患者。多项研究表明SGLT-2is可以影响代谢状态,减少心血管事件发生和改善糖尿病肾病预后。关于SGLT-2is如何让T2DM患者获益,目前机制仍在探索中。本文对SGLT-2is作用机制进一步研究,有望为后续治疗提供依据。     

特殊人群患2型糖尿病的降糖药物选择策略

患2型糖尿病（T2DM）的特殊人群因年龄、性别、生理和病理状态的不同,在药物治疗方面与普通T2DM患者存在明显差异。本文根据最新循证医学证据,系统综述了T2DM合并症或并发症患者、老年患者、儿童患者、妊娠期/哺乳期妇女等特殊人群的降糖药物选择策略。在制定T2DM特殊人群的个体化降糖治疗方案时,医师需根据其不同特征,依据最新循证医学证据,合理选用降糖药物,从而精准降糖,并预防和延缓糖尿病并发症的发生,例如对于合并动脉粥样硬化性心血管疾病、心力衰竭、肾病、肝病的T2DM患者,可在二甲双胍基础上加用钠-葡萄糖共转运蛋白2抑制剂或胰高血糖素样肽1受体激动剂;对于合并胃轻瘫的T2DM患者,建议使用胰岛素;对于合并高尿酸血症或痛风的T2DM患者,应优先选用兼有降尿酸作用的降糖药物,并慎用胰岛素;对于合并骨质疏松症的T2DM患者,应选用不影响骨代谢或有骨保护作用的降糖药物;对于T2DM老年患者,建议优先选择低血糖风险较低的药物单用或联合使用。     

肠促胰素类药物与2型糖尿病的低血糖风险

接受药物治疗的2型糖尿病患者低血糖临床表现多样,严重低血糖危害极大,是2型糖尿病患者血糖达标的主要障碍。传统降糖药物中,低血糖风险高的药物包括胰岛素、磺脲类、格列奈类;低血糖风险低的药物包括二甲双胍、α-糖苷酶抑制剂、噻唑烷二酮类。对于低血糖高危人群建议使用低血糖风险较小的药物。肠促胰素类药物是近年新崛起的降糖药物,包括外源性GLP-1受体激动剂和DPP-4抑制剂两大类,可葡萄糖依赖性降糖。因其降糖疗效确切同时低血糖风险较低,已成为2型糖尿病单药和联合治疗的首选药物之一。     

胰岛素治疗口服降糖药失效的2型糖尿病的临床观察

目的：探讨继发性口服降糖药物失效的2型糖尿病（T2DM）患者,应用预混人胰岛素类似物替代口服促胰岛素分泌类药物,配合二甲双胍或（和）α-糖苷酶抑制剂,对T2DM及其并发症的控制效果.方法：符合参与观察对象的T2DM患者50名,进行12周的随访,通过患者自身2种治疗方案前后血糖、血脂等指标的变化进行比较.结果：血糖、血压、糖化血红蛋白和甘油三酯下降,有显著性差异（P〈0.01）.结论：对继发性口服降糖药物失效的T2DM患者,应用预混人胰岛素类似物替代口服促胰岛素分泌类药物,配合二甲双胍或（和）α-糖苷酶抑制剂,对T2DM患者血糖、血脂控制水平,提高血糖达标率有促进作用.     

心力衰竭治疗新靶点-Galectins．3

尽管心力衰竭（HF）的药物治疗近年来有了较大进展,但HF患者预后仍很差。针对HF发病早期行药物治疗是近年来研究的一个重点。Galectin．3（Gal-3）在心室重塑和HF病理生理发展过程中起重要作用,可作为HF治疗的靶点。Gal-3水平升高的HF患者可从醛固酮拮抗剂治疗中获益。本文简要综述以Gal-3水平为指导的HF患者个体化治疗。     

高通量血液透析对维持性血液透析患者β2-微球蛋白及生活质量的影响

目的前瞻性研究高通量血液透析对维持性血液透析患者β2-微球蛋白及生活质量的影响。方法58例血液透析患者随机分成低通量血液透析组（LF组）31例和高通量血液透析组（HF组）27例,分别使用低通量血液透析器和高通量血液透析器,观察48周,观察2组患者β2-微球蛋白、超敏C反应蛋白（hs-CRP）及主观全面营养评价（SGA）的变化。结果 2组患者的脱落率、Hb、AIb、β2-微球蛋白、体质量指数（BMI）、主观全面营养评价（SGA）评分与治疗前比较明显改善;且HF组改善优于LF组,差异有统计学意义（P〈0.05）。结论高通量血液透析较低通量血液透析可以更多清除血液透析患者的β2-微球蛋白和提高生活质量。     

胰高血糖素样肽-1及相关降糖药物的研究进展

胰高血糖素样肽-1（glucagon-like peptide-1,GLP-1）是近几年糖尿病治疗药物研究的热点之一,具备多重降血糖作用。它的两大类药物：GLP-1类似物和二肽基肽酶-Ⅳ抑制剂作为新的降糖药物相继完成临床研究,并在糖尿病治疗中发挥越来越重要的作用。本文就GLP-1的结构、药理作用以及两类相关降糖药物的临床应用作一概述。     

丹蛭降糖胶囊改善2型糖尿病患者血管内皮粘附状态及炎症损伤的临床观察

目的观察具有益气养阴活血功效的纯中药制剂丹蛭降糖胶囊（DJC）对2型糖尿病（T2DM）患者血管内皮粘附状态及炎症损伤的影响,探讨其延缓2型糖尿病血管并发症的机理。方法将46例2型糖尿病气虚阴亏血瘀证患者随机分为治疗组（n=24）和对照组（n=22）（2组基线水平无显著性差异）,2组均常规给予西药口服降糖治疗;治疗组在此基础上,加用丹蛭降糖胶囊,2组疗程均为20周。治疗前后分别检测空腹及餐后2h血糖（PG）、血清胰岛素（INS）和胰岛素抵抗指数（IR）、可溶性血管细胞粘附分子-1（sVCAM-1）、血清超敏c反应蛋白（hs-CRP）水平。结果治疗组在应用丹蛭降糖胶囊20周后,INS、IR、sVCAM-1含量及hs-CRP水平均明显改善（P〈0.05）。结论丹蛭降糖胶囊能干预2型糖尿病患者血管内皮粘附状态及炎症反应,改善内皮损伤,对于延缓2型糖尿病血管并发症有积极的意义。     

sST2 MMP-2 MMP-9与急性心肌梗死并发心力衰竭患者预后的相关性

目的 探讨血清可溶性生长刺激表达基因2蛋白（sST2）和基质金属蛋白酶（MMP）-2、MMP-9水平与急性心肌梗死（AMI）并发心力衰竭（HF）患者预后的相关性。方法 选取2017年5月至2018年5月在海南省第三人民医院住院的AMI患者149例,记录患者入院后相关数据,检测入院时血清sST2、MMP-2、MMP-9水平,根据住院期间是否并发HF分为HF组（54例）和无HF组（95例）,出院后随访12个月,根据是否出现恶性HF、心源性死亡等将AMI并发HF患者分为预后不良组（n=16）和预后良好组（n=38）,比较HF组和无HF组以及预后不良组和预后良好组血清sST2、MMP-2、MMP-9水平,并采用受试者工作特征（ROC）曲线分析sST2、MMP-2、MMP-9对AMI并发HF患者预后的预测价值。结果 HF组血清sST2、MMP-2、MMP-9水平均高于无HF组,差异有统计学意义（P<0.05）;HF组不良事件发生率为29.63%（16/54）,预后不良组血清sST2、MMP-2、MMP-9水平均高于预后良好组,差异有统计学意义（P<0.05）;sST2、MMP-2、MMP-9预测AMI并发HF患者预后的曲线下面积（AUC）分别为0.888、0.938、0.715。结论 AMI并发HF患者血清sST2、MMP-2、MMP-9明显增高,高水平血清sST2、MMP-2、MMP-9可能提示患者预后不良,sST2、MMP-2、MMP-9对患者预后有较好的预测价值。     

卫生院2型糖尿病住院患者降糖药物使用情况调查分析

目的 了解该卫生院2型糖尿病住院患者降糖药物使用情况，为基层医疗卫生机构规范使用降糖药物提供参考。方法 从寿光市圣城街道卫生院的医院信息系统中选取2019年1—12月765例2型糖尿病住院患者的临床资料，分析降糖药物使用情况。结果 使用频次前三位的降糖药物分别是胰岛素（74.1%,567/765）、双胍类（63.9%,489/765）、磺脲类（27.6%,211/765）；使用单药治疗的患者常用降糖药物居前两位的是胰岛素（74.6%,144/193）、双胍类14.0%(27/193)，二联治疗居前两位的是双胍类+胰岛素（47.6%,156/328）、双胍类+磺脲类（20.4%,67/328）；应用降糖药物品种共计32种，使用前三位的分别是二甲双胍（63.9%,489/765）、格列美脲（25.9%,198/765）、诺和灵30R(25.2%,193/765)；口服降糖药物+注射降糖药联合治疗者占比最高（55.6%,425/765）。结论 该卫生院2型糖尿病住院患者降糖药物治疗方案基本合理，符合《中国2型糖尿病防治指南（2020年版）》《国家基层糖尿病防治管理指南（2018）》推荐的路径...     

沙库巴曲缬沙坦在心衰治疗中的应用:从临床试验到真实世界

传统心衰药物治疗方案在一定程度上可改善患者心衰症状,但无法有效降低患者死亡率及因心衰住院率,因此开发新型心衰治疗药物迫在眉睫。2015年,具有双重作用机制的血管紧张素受体脑啡肽酶抑制剂（angiotensin receptor neprilysin enzyme inhibitor,ARNI）沙库巴曲缬沙坦被美国食品药品监督管理局（the Food and Drug Administration,FDA）批准上市,为心衰患者的治疗带来了新的希望。本文综述了沙库巴曲缬沙坦的药学性质,更新了相关临床试验结果,并介绍其在真实世界中的应用效果,以期为临床心衰药物治疗提供参考。     

Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice

Beta-blockers have become one of the cornerstones of treatment of patients with heart failure (HF) and depressed left ventricular function, but in clinical practice only 30–35 % of patients achieve the therapeutic target dose as established in randomized clinical trials. Moreover, high resting heart rate (HR) has emerged as a simple but relevant risk factor for cardiovascular events, including coronary artery disease and HF; also, it was found to have an independent prognostic value in patients with HF. Evidence that HR could be considered a good parameter to evaluate the quality of treatment in patients with HF has been suggested; of note, many patients maintain a resting HR ≥70 beats per minute despite optimal beta-blocker therapy. In recent years, a new drug able to reduce HR, ivabradine, has been introduced in clinical practice, and its use in the clinical setting of HF patients has been recommended by current European Society of Cardiology (ESC) guidelines. Here we review the evidence of the prognostic role of HR in systolic HF and the potential relationship between HR lowering and the beneficial effects of beta-blockers; we will also analyze the reasons why an appropriate use of these drugs is seldom achieved in clinical practice, and review the evidence for the use of ivabradine in systolic HF in the clinical setting.     

Current and emerging pharmacologic options for the management of patients with chronic and acute decompensated heart failure

Introduction: For many years heart failure (HF) was known as a fatal disease with an ominous prognosis. In the last decades better understanding of the pathophysiological mechanisms underlying HF has resulted in major breakthrough in the management and improvement in the natural history of this clinical syndrome.

Areas covered: The review is focused on current and upcoming pharmacological therapies in patients with chronic and acute HF, starting with brief overview of drugs which improve the outcomes in patients with chronic HF with reduced ejection fraction (EF) including neurohormonal antagonists, angiotensin receptor neprilysin inhibitor and If- channel inhibitor, then presenting the summary of symptomatic treatment, the pharmacotherapy in chronic HF with preserved and mid-range EF and in acute HF. Finally, we report the emerging pharmacologic options and ongoing clinical trials and future directions in pharmacotherapy.

Expert commentary: The guidelines-recommended therapies in HF with reduced EF need to be widely implemented into the everyday clinical practice. Better clinical characterization of HF with preserved, mid-range EF and acute HF, with better understanding of the underlying pathophysiological mechanisms may ultimately result in a development of effective strategies improving ominous outcomes in these patients.     

Potential new drug treatments for congestive heart failure

Introduction: The prevalence of heart failure (HF) has increased globally in recent decades. Advances in our understanding of underlying pathophysiologic mechanisms have given rise to new therapies for treating the growing HF population. Nonetheless, morbidity and mortality associated with HF and its financial implications are daunting. Thus, novel therapies that can improve the natural history of HF patients are urgently needed.

Areas covered: This article reviews new investigational drugs being developed for the treatment of both acute decompensated heart failure (ADHF) and chronic heart failure with reduced ejection fraction (HFrEF). It presents the background of these drugs with a focus on their mechanism of action, their pharmacology, evidence from clinical studies and their potential role in HF management.

Expert opinion: The mortality benefit associated with serelaxin treatment in the RELAX-HF trial is being tested in RELAX-AHF II, while two other drugs, ularitide and TRV027, are also being evaluated in ADHF patients. Two new agents for the treatment of chronic HFrEF, LCZ696 and ivabradine, have been recently been approved for use by the FDA and four novel agents which have shown considerable promise in early studies, omecamtiv mecarbil, vericiguat, finerenone, and neuregulin, are currently being evaluated in late-phase clinical trials.     

B-type natriuretic peptide for diagnosis and therapy

Brain natriuretic peptide (BNP) plays an important role in cardiovascular homeostasis. Plasma BNP increases markedly in left ventricular dysfunction from several causes, and its levels in heart failure (HF) correlate with symptoms severity. BNP has recently emerged as a potentially important clinical marker for the diagnosis of HF in patients with unexplained dyspnea. Other clinical applications of BNP, such as screening for asymptomatic ventricular dysfunction, establishing the prognosis or guiding the titration of drug therapy, are under investigation and have not yet been sufficiently validated for widespread clinical use. Laboratory-based and point-of-care analyses are available for BNP and N-terminal proBNP as fully-automated immunoassays. Several patented inventions and reagents for the diagnosis of various heart pathologies provide helpful information, particularly in conjunction with other clinical tests. They also have prognostic value for future cardiovascular events. Patents owned by Scios Inc. recommended recombinant BNP for managing acute decompensated HF. However, this treatment apparently has safety problems and no proven clinical advantage over existing treatments in terms of improved survival and prevention of subsequent hospitalizations.     

改善心力衰竭能量代谢的潜在药物研究进展

心力衰竭（HF）是一个全球性的公共卫生问题,发病率和死亡率都很高。研究表明,HF是由严重的能量代谢紊乱引起的,导致心脏能量供应不足。这种能量缺乏会导致心脏泵血功能障碍和全身其他器官能量代谢的衰竭。针对HF的疗法主要通过降低心率和心脏前负荷和后负荷、对症治疗或延缓疾病的发展来发挥作用。然而,针对心脏能量代谢的药物却尚未研发出来。本文概述健康心脏中能量代谢的主要特征、HF期间的代谢变化,并讨论通过能量代谢来改善心脏功能的药物,为治疗HF药物的研发和应用提供新的研究方向。     

钠-葡萄糖协同转运蛋白抑制剂治疗心力衰竭的研究进展

钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是一类新型口服降糖药.大量临床研究表明:SGLT2i可通过非胰岛素依赖机制降低心血管疾病病死率和心力衰竭住院率,有望成为心力衰竭治疗的基础药物之一.本综述总结了SGLT2i治疗心力衰竭的潜在机制和相关临床研究进展.     

钠-葡萄糖协同转运蛋白2抑制剂治疗心力衰竭及其作用机制研究进展

心血管疾病是当今世界威胁人类健康的头号杀手,心力衰竭是众多心血管疾病的终点。随着人口老龄化的发展和新的心力衰竭亚型的出现,传统抗心力衰竭药物的疗效难以令人满意。近年来,新型降糖药钠–葡萄糖协同转运蛋白2(SGLT2)抑制剂在心血管结局研究中表现出了良好的效果,展现了此类药物巨大的研究价值。从临床试验结果、心脏功能改善和作用机制分析3个方面综述SGLT2抑制剂治疗心力衰竭的研究进展。     

厄贝沙坦对心力衰竭患者24小时心率变异性的影响

目的探讨心力衰竭患者24 h心率变异性(HRV)的变化及厄贝沙坦对心脏自主神经系统功能的影响。方法130例不同程度的心力衰竭患者随机分为2组,厄贝沙坦试验组(68例)和对照治疗组(62例),分别测定治疗前后24 h的心率变异性。结果心力衰竭患者心率变异性各时段没有区别(P>0.05),说明HF患者HRV昼夜节律消失。而厄贝沙坦能显著提高心力衰竭患者的24 h心率变异性,恢复昼夜节律性(P<0.05)。结论HRV可作为预测心力衰竭患者的病情和预后的监测指标,而厄贝沙坦对心力衰竭患者的心脏自主神经系统功能产生有益的影响。     

Efficacy and Safety of the Use of Pulmonary Arterial Hypertension Pharmacotherapy in Patients with Pulmonary Hypertension Secondary to Left Heart Disease: A Systematic Review

Pulmonary hypertension (PH) is often caused by left heart disease (LHD) such as heart failure (HF) or valvular heart disease. Historically, few randomized controlled trials have evaluated the off-label use of medications for treating pulmonary arterial hypertension (PAH) in patients with PH-LHD. However, multiple randomized controlled trials have been published over the last decade that investigated their use in patients with PH-LHD. In addition, recent updates in the classification and definitions of PH have led to an improved recognition of PH-LHD phenotypes, notably combined post-capillary and pre-capillary PH and isolated post-capillary PH. In this systematic review, we show that PAH medications should not be recommended in two distinct HF populations: patients with HF without definitive PH diagnosis and patients with isolated post-capillary PH due to HF. In addition, the use of bosentan or macitentan is not recommended in patients with combined post-capillary and pre-capillary PH due to HF, but sildenafil may be considered to improve pulmonary hemodynamics and exercise capacity in patients with combined post-capillary and pre-capillary PH due to HF. Riociguat 2 mg 3 times daily may also be considered to improve pulmonary hemodynamics in patients with combined post-capillary and pre-capillary PH due to heart failure with reduced ejection fraction but not heart failure with preserved ejection fraction. The postoperative use of sildenafil in the setting of PH after valvular heart disease intervention was evaluated. Limited clinical data and safety concern warrants caution with the postoperative use of sildenafil in patients with PH due to valvular heart disease. Despite recent advances in the understanding of PAH medications for patients with PH-LHD, uncertainty remains about their utility in distinct subgroups. Nonetheless, PAH pharmacotherapy should generally be avoided for most patients with PH-LHD.