SGLT2抑制剂治疗2型糖尿病的相关研究

钠-葡萄糖协同转运蛋白2( SGLT2)存在于近端肾小管上皮细胞,在肾脏血糖的重吸收中发挥重要作用,因此选择性抑制SGLT2活性,从而特异性抑制肾脏对葡萄糖的重吸收,增加尿糖排泄可以达到降糖目的.目前研发的SGLT2抑制剂包括T-1095、BI-10773、dapagliflozin等.SGLT2抑制剂与体重、低血糖、糖尿病肾病、泌尿系统感染及口渴、多饮、多尿症状的关系未明确,目前已有大量研究证明了其有效性及安全性,这将为糖尿病患者提供一种新的降糖途径.     

SGLT2抑制剂降低糖尿病患者心血管风险的研究进展

Na+-葡萄糖协同转运蛋白(SGLT)2抑制剂是一类新型降糖药物,通过抑制肾脏近端小管SGLT2对葡萄糖的重吸收而降低血糖.EMPA-REG OUTCOME试验表明,恩格列净可降低合并高危心血管风险的糖尿病患者的主要不良心血管事件.SGLT2抑制剂可能通过降低血压、降低血容量、促进钠盐排出、对肾脏血流动力学的改善、减轻体重、增加胰岛素敏感性、抑制心肌重构、降低尿酸等发挥其心血管保护作用,但其确切机制目前仍未明确.     

SGLT2抑制剂对糖尿病小鼠炎性因子表达的影响

目的 探讨糖尿病小鼠血管内皮炎性因子是否表达,SGLT2抑制剂对其作用的影响。方法将8周龄SPF级雄性CIR小鼠腹腔注射低剂量STZ(50 mg/kg),建模持续6 d,对照组皮下注射生理盐水,造模成功,随机分成对照组（普通饲料）,模型组（普通饲料）和治疗组（普通饲料+达格列净干预治疗）,动态观察4周、8周、12周末小鼠的体重、血糖变化,分别应用EILSA法检测血浆内肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、单核细胞趋化因子-1(MCP-1)表达变化和Western blot法测定血管壁各炎性因子蛋白的表达。结果 各组小鼠体重和血糖在不同时间段比较,差异有统计学意义（P<0.05）。与对照组比较4周模型组血浆内TNF-α显著升高,差异有统计学意义（P<0.01）,而4周模型组血浆内IL-1β、MCP-1表达亦增多,差异无统计学意义（P>0.05）;与对照组比较8周、12周模型组血浆内TNF-α、IL-1β、MCP-1表达变化明显升高,差异有统计学意义（P<0.05）;与模型组比较4周治疗组血浆内TNF-α、IL-1β、MCP-1表达变化不明显,...     

SGLT2抑制剂在各种原因所致慢性心力衰竭的研究进展

随着医学的不断发展,众多疾病的治疗有了突破性进展,但各种原因所致的慢性心力衰竭（心衰）仍对人类的健康发出巨大挑战,新的治疗靶点迫在眉睫。钠-葡萄糖协同转运蛋白-2(SGLT2)抑制剂作为近些年新兴起的降糖药物,各项研究结果表明其除具有良好的降糖效果外,还对糖尿病及非糖尿病患者的心、肾功能表现出良好的保护作用。但其对心脏本身是否直接受益,以及具体作用机制,目前尚未明确。本文就其可能的作用机制、目前临床研究结果、指南相关推荐情况进行总结,探讨其目前进展。     

SGLT2抑制剂联合厄贝沙坦治疗糖尿病肾病疗效的Meta分析

目的 系统评价钠-葡萄糖协同转运蛋白2(sodium-dependent glucose transporters 2, SGLT2)抑制剂联合厄贝沙坦治疗糖尿病肾病的疗效。方法 检索中国知网、维普、万方、pubmed等数据库,检索时间:各数据库建库至2021年12月,收集SGLT2抑制剂联合厄贝沙坦治疗糖尿病肾病的随机对照试验。设定纳排标准,采用Cochrane偏倚风险评判标准进行文献质量评估,使用RevMan 5.4软件进行Meta分析。结果 共纳入10篇文献,涉及828例糖尿病肾病患者。SGLT2抑制剂联合厄贝沙坦组比单用厄贝沙坦组更能提高糖尿病肾病有效率[RR=1.29,95%CI(1.19,1.40),P<0.000 01],改善24 h尿蛋白定量[SWD=-1.44,95%CI(-2.07,-0.81),P<0.000 01]、尿白蛋白排泄率[SMD=-1.09,95%CI(-1.93,-0.25),P=0.01]、肾小球滤过率[MD=7.83,95%CI(2.51,13.16),P=0.004],血肌酐[MD=-16.87,95%CI(-29.1,-4.65)...     

SGLT2i在合并糖尿病动脉粥样硬化性心血管疾病中的作用研究进展

糖尿病是一种全球流行病,血糖控制不佳是导致心血管疾病患者死亡的主要原因之一.作为新型降糖药,钠-葡萄糖共转运体2抑制剂(SGLT2i)由于其在临床和基础研究中表现出卓越的心血管系统保护作用而倍受关注.前期针对SGLT2i的大型随机对照试验(EMPA-RED研究、CANVAS研究、DELCARE TIMI-58研究)均证...     

SGLT2抑制剂减少2型糖尿病患者并发心律失常的研究进展

钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）是一种新型降糖药,通过抑制肾脏近端小管对钠及葡萄糖的重吸收降低血糖。研究证实SGLT2i能减少心力衰竭的发生率、住院率及全因死亡率。多项研究提示SGLT2i可以通过减轻心脏负荷、改善离子稳态、调节线粒体功能及抑制交感神经活性等机制减少心律失常的发生。该文介绍SGLT2i通过减少心律失常发生使心血管系统获益的研究进展。     

钠-葡萄糖协同转运蛋白2抑制剂对2型糖尿病合并心房颤动影响的研究进展

心房颤动(AF)是临床常见心律失常,显著增加脑卒中、心力衰竭等风险,严重危害人类健康.T2DM是常见慢性疾病之一,可增加AF风险,与AF患者心血管死亡风险增加相关.T2DM合并AF的病理生理机制尚不明确,可能与心房电、结构及自主神经重构相关.SGLT2i是一种新型降糖药,除有显著降糖效果外,还降低T2DM患者AF风险....     

SGLT2抑制剂在肥胖2型糖尿病治疗中的价值

肥胖是2型糖尿病（T2DM）的主要危险因素之一,大部分T2DM患者合并超重或肥胖。钠-葡萄糖共转运蛋白2 （sodium-glucose cotransporter2,SGLT2）抑制剂通过抑制肾脏近曲小管的葡萄糖重吸收,增加葡萄糖从尿液排出而发 挥降糖作用,同时还具有降压、调脂、减重、改善肝功能、降尿酸等效应,从而缓解肥胖T2DM患者的代谢紊乱。 SGLT-2抑制剂是治疗肥胖T2DM的新途径,对改善远期预后具有重要的意义。     

SGLT2抑制剂对2型糖尿病患者尿酸代谢影响的研究进展

高尿酸血症(HUA)常与2型糖尿病患者的主要不良心血管事件、慢性终末期肾病有关。钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)是一类选择性抑制肾脏近曲小管葡萄糖重吸收的新型口服降糖药物,其兼有降糖之外的获益。本文就SGLT2i对2型糖尿病患者尿酸代谢的影响的研究进展作一综述。     

吡格列酮对2型糖尿病患者胰岛素敏感性和脂代谢的影响

目的观察吡格列酮对2型糖尿病患者胰岛素敏感性和脂代谢的影响。方法选择我院20例2型糖尿病患者，单纯饮食控制或口服磺脲类药物血糖控制不良时加用吡格列酮。开始剂量为15mg／d，2周后视空腹血糖情况调整剂量为15—30mg／d，治疗12周。结果患者治疗前、后FBG、FINS、IAI、2hPG、2hPINS、TG、LDL—C、HDL—C间差异均有显著性意义（P〈0．05）。结论吡格列酮治疗2型糖尿病可显著增加患者的胰岛素敏感性且改善脂代谢。     

Blood pressure effects of sodium–glucose co-transport 2 (SGLT2) inhibitors

Management of hypertension in diabetes is critical for reduction of cardiovascular mortality and morbidity. While blood pressure (BP) control has improved over the past two decades, the control rate is still well below 50% in the general population of patients with type 2 diabetes mellitus (T2DM). A new class of oral glucose-lowering agents has recently been approved; the sodium–glucose co-transporter 2 (SGLT2) inhibitors, which act by eliminating large amounts of glucose in the urine. Two agents, dapagliflozin and canagliflozin, are currently approved in the United States and Europe, and empagliflozin and ipragliflozin have reported Phase 3 trials. In addition to glucose lowering, SGLT2 inhibitors are associated with weight loss and act as osmotic diuretics, resulting in a lowering of BP. While not approved for BP-lowering, they may potentially aid BP goal achievement in people within 7–10 mm Hg of goal. It should be noted that the currently approved agents have side effects that include an increased incidence of genital infections, predominantly in women. The approved SGLT2 inhibitors have limited use based on kidney function and should be used only in those with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m² for dapagliflozin and ≥45 mL/min/1.73 m² for canagliflozin. Cardiovascular outcome trials are ongoing with these agents and will be completed within the next 4–5 years.     

Different Acute and Chronic Effects of Acipimox Treatment on Glucose and Lipid Metabolism in Patients with Type 2 Diabetes

To study whether therapeutic reduction of non-esterified fatty acids (NEFA) can be used to improve glucose metabolism, we administered the antilipolytic agent, acipimox, 250 mg four times daily for 4 weeks in eight obese Type 2 diabetic patients. Glucose and NEFA metabolism were assessed before and after treatment with a two-step euglycaemic hyperinsulinaemic clamp (0.25 and 1 ***mU kg^?1 min^?1 insulin) combined with infusions of [3–³H] glucose and [1–¹⁴C] palmitate. Three days of acipimox treatment reduced 24-h serum NEFA levels by 10%, but the difference disappeared after 4 weeks of treatment mainly due to a two-fold rise in morning NEFA concentrations (p < 0.01). After 3 days of acipimox treatment, fasting and 24-h plasma glucose and serum triglyceride concentrations were significantly reduced (p < 0.05), but no longer after 4 weeks of treatment. Despite the rebound rise in NEFA, acute administration of acipimox still inhibited both oxidative and non-oxidative NEFA metabolism in the basal state (p < 0.01 – 0.001) and during insulin infusion (p < 0.05 – 0.001). Inhibition of NEFA metabolism was associated with increased insulin-stimulated glucose uptake (from 3.56 ± 0.28 to 5.14 ± 0.67 μmol kg^?1 min^?1, p < 0.05), mainly due to stimulation of non-oxidative glucose disposal (from 1.74 ± 0.23 to 3.03 ± 0.53 μmol kg^?1 min^?1, p < 0.05). In conclusion, acipimox administered acutely inhibits NEFA appearance (lipolysis), which is associated with improved glucose uptake. However, after 4 weeks of treatment, the beneficial effects on NEFA and glucose metabolism are outweighed by a marked rebound rise in fasting NEFA concentrations. The results emphasize the problems using acipimox as a means to improve glucose tolerance in patients with Type 2 diabetes.     

射血分数保留型心力衰竭合并2型糖尿病的研究进展

【摘要】射血分数保留型心力衰竭（Heart Failure with Preserved Ejection Fraction, HFpEF）,是一种特殊类型的心力衰竭,约占全部心力衰竭患者的50%。HFpEF的确切的发病机制尚不完全清楚。2型糖尿病(Type 2 Diabetes Mellitus, DM)在HFpEF患者中有较高的发病率,2型糖尿病合并射血分数保留型心力衰竭（Diabetes Mellitus-Heart Failure with Preserved Ejection Fraction, DM-HFpEF）患者在临床上常表现为心力衰竭症状重、治疗效果差、最佳治疗方法仍不明确,考虑HFpEF患者的发病机制与2型糖尿病有关。     

Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2

Non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus type 2 commonly coexist as a manifestation of metabolic syndrome. The presence of diabetes promotes the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH) and cirrhosis, and the presence of NAFLD increases the risk of diabetic complications. This coexistence affects a large part of the population, imposing a great burden on health care systems worldwide. Apart from diet modification and exercise, recent advances in the pharmacotherapy of diabetes offer new prospects regarding liver steatosis and steatohepatitis improvement, enriching the existing algorithm and supporting a multifaceted approach to diabetic patients with fatty liver disease. These agents mainly include members of the families of glucagon-like peptide-1 analogues and the sodium-glucose co-transporter-2 inhibitors. In addition, agents acting on more than one receptor simultaneously are presently under study, in an attempt to further enhance our available options.     

SGLT2 inhibition and glucagon secretion in humans

With the increasing prevalence of type 2 diabetes (T2D), therapies aimed at delineating diabetes pathophysiology and understanding their mechanisms of action are of critical importance. As such, growing interest in the clinical pharmacology of sodium–glucose cotransporter 2 (SGLT2) and its inhibition by gliflozins in the treatment of T2D is becoming increasingly evident. SGLT2 inhibition results in urinary glucose excretion, thereby reducing blood glucose levels. The importance of this homoeostasis mechanism is evident from several clinical trials demonstrating that patients taking this class of compounds have reductions in glycaemia, body weight and blood pressure compared with other antidiabetic agents. Yet, while such outcomes are very encouraging, some studies have reported elevated plasma glucagon levels and endogenous glucose production (EGP), two traits that are already prevalent in T2D. However, these findings were later explained by the specific expression of SGLT2 by pancreatic alpha cells, where glucagon secretion is directly regulated. Although conflicting data are now emerging on SGLT2 regulation of glucagon secretion, as SGLT2 is not expressed in the intestines, circulating glucagon concentrations are most likely of pancreatic origin. Thus, the present review considers the mechanism of action of SGLT2 inhibitors in the regulation of glucagon secretion, and the discrepancies in data from mice compared with people. The pragmatic use of human islets to accurately decipher SGLT2 inhibition in the regulation of glucagon secretion is also discussed.