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| 1 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 2 | Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association显示文摘 | Alan S. Go Dariush Mozaffarian Véronique L. Roger Emelia J. Benjamin Jarett D. Berry William B. Borden Dawn M. Bravata Shifan Dai Earl S. Ford Caroline S. Fox Sheila Franco Heather J. Fullerton Cathleen Gillespie Susan M. Hailpern John A. Heit Virginia J. | 2013 | Circulation2013，，1： | 5 |
| 3 | Heart Disease and Stroke Statistics—2011 Update: A Report From the American Heart Association显示文摘 | Véronique L. Roger Alan S. Go Donald M. Lloyd-Jones Robert J. Adams Jarett D. Berry Todd M. Brown Mercedes R. Carnethon Shifan Dai Giovanni de Simone Earl S. Ford Caroline S. Fox Heather J. Fullerton Cathleen Gillespie Kurt J. Greenlund Susan M. Hailpern | 2011 | Circulation2011，，4： | 4 |
| 4 | Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation显示文摘Regulatory T cells(Tregs)play a pivotal role in immune-tolerance,and loss of Treg function can lead to the development of autoimmunity.Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery,where they suppress self-reactive effector T cells(Teff)responses.Recently,we showed that OX40L(TNFSF4)is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation(CAP-independent)in the presence of low-dose IL-2.Therefore,we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg(tTreg)development.Development of tTregs is a two-step process:Strong T-cell receptor(TCR)signals in combination with co-signals from the TNFRSF members facilitate tTreg precursor selection,followed by a TCR-independent phase of tTreg development in which their maturation is driven by IL-2.Therefore,we investigated whether OX40 signaling could also play a critical role in the TCR-independent phase of tTreg development.OX40−/−mice had significantly reduced numbers of CD25−Foxp3low tTreg precursors and CD25+Foxp3+mature tTregs,while OX40L treatment of WT mice induced significant proliferation of these cell subsets.Relative to tTeff cells,OX40 was expressed at higher levels in both murine and human tTreg precursors and mature tTregs.In ex vivo cultures,OX40L increased tTreg maturation and induced CAP-independent proliferation of both murine and human tTregs,which was mediated through the activation of AKT-mTOR signaling.These novel findings show an evolutionarily conserved role for OX40 signaling in tTreg development and proliferation,and might enable the development of novel strategies to increase Tregs and suppress autoimmunity. | Prabhakaran Kumar Alejandra Marinelarena Divya Raghunathan Vandhana K Ragothaman Shikha Saini Palash Bhattacharya Jilao Fan Alan L Epstein Ajay V Maker Bellur S Prabhakar | 2019 | Cellular & Molecular Immunology2019，16，2： | 4 |
| 5 | Executive Summary: Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association显示文摘 | Alan S. Go Dariush Mozaffarian Véronique L. Roger Emelia J. Benjamin Jarett D. Berry William B. Borden Dawn M. Bravata Shifan Dai Earl S. Ford Caroline S. Fox Sheila Franco Heather J. Fullerton Cathleen Gillespie Susan M. Hailpern John A. Heit Virginia J. | 2013 | Circulation2013，，1： | 4 |
| 6 | Hemoglobin A1c in early postpartum screening of women with gestational diabetes显示文摘AIM:To assess the utility of hemoglobin A1c(HbA1c) in the early postpartum screening of women with gestational diabetes mellitus(GDM).METHODS:Over a 3 years period,HbA1c estimations were undertaken in addition to and simultaneously with the traditional oral glucose tolerance test(OGTT),in 203 women with GDM as a part of early postpartum screening for dysglycaemia,at 6 wk post-partum.World Health Organization criteria was used for diagnosing diabetes:fasting blood glucose(FBG) ≥ 7.0 mmol/Land/or 2-h postprandial blood glucose(PPBG) ≥ 11.1 mmol/L and/or HbA1c ≥ 48 mmol/mol;and impaired glycaemiastate:impaired fasting glucose 6.1-6.9 mmol/L and/or impaired glucose tolerance 7.8-11.0 mmol/L and/or HbA1c:42-47 mmol/mol.RESULTS:Mean FBG,2-h PPBG and HbA1c were 4.9 ± 0.7 mmol/L,5.6 ± 2.0 mmol/L and 38 ± 5 mmol/mol respectively.FBG,2-h PPBG and HbA1c detected 6(3%),7(3.5%) and 11(5.4%) cases of diabetes respectively,and 11(5.4%),25(12.3%) and 23(11.3%) cases of pre-diabetes state respectively.HbA1c values ≥ 48 mmol/mol(≥ 6.5%) showed a diagnostic sensitivity of 71.4% and specificity of 98.5% for diabetes in comparison to OGTT in receiver operating characteristics curve analysis.At HbA1c cut-off 44 mmol/mol,sensitivity and specificity were 100% and 92.3% respectively [area under the curve:0.98(95%CI:0.96-1.00)].Sensitivity and specificity for detecting high risk 'impaired glycaemia' state [HbA1c 42 mmol/mol(6.0%)] were 28% and 80%,respectively.CONCLUSION:HbA1c level ≥ 48 mmol/mol(≥ 6.5%) has reasonable sensitivity and high specificity in comparison to OGTT for early postpartum screening of diabetes in GDM.At 6 th week postpartum screening,if FBG is normal and HbA1c < 44 mmol/mol OGTT is not recommended. | Mahesh V Katreddy Joseph M Pappachan Sarah E Taylor Radha Indusekhar Ananth U Nayak Alan M Nevill | 2013 | World Journal of Diabetes2013，4，3： | 2 |
| 7 | Executive Summary: Heart Disease and Stroke Statistics—2012 Update: A Report From the American Heart Association显示文摘 | Véronique L. Roger Alan S. Go Donald M. Lloyd-Jones Emelia J. Benjamin Jarett D. Berry William B. Borden Dawn M. Bravata Shifan Dai Earl S. Ford Caroline S. Fox Heather J. Fullerton Cathleen Gillespie Susan M. Hailpern John A. Heit Virginia J. Howard Bret | 2012 | Circulation2012，，1： | 2 |
| 8 | Rich and Poor Countries in Neoclassical Trade and Growth 显示文摘 | Deardorff Alan V | 2001 | The Economic Journal2001，，111： | 1 |
| 9 | Estimates of the elasticities of substitution between imports and home goods for the United States显示文摘 | Clinton R S Robert M S Alan V D | | 0，，03： | 1 |
| 10 | Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association显示文摘 | Alan S. Go Dariush Mozaffarian Véronique L. Roger Emelia J. Benjamin Jarett D. Berry William B. Borden Dawn M. Bravata Shifan Dai Earl S. Ford Caroline S. Fox Sheila Franco Heather J. Fullerton Cathleen Gillespie Susan M. Hailpern John A. Heit Virginia J. | 2013 | Circulation2013，，1： | 1 |
| 11 | 3 ' -Minor groove binder-DNA probe increase sequence specificity at PCR extension temperatures显示文摘 | IGOR V K IRINA A A ALAN M | 2000 | Nucleic Acids Res2000，28，2： | 1 |
| 12 | Fault-tolerant rate-monotonic first-fit scheduling in hard-real-time systems显示文摘 | Alan A Bertossi Luigi V Mancini Federico Rossini | 1999 | IEEE Transactions on Parallel and Distributed Systems1999，10，9： | 1 |
| 13 | Dendritic cell subset ratio in tolerant,weaning and non-tolerant liver recipients is not affected by extent of immunosuppression显示文摘 | George V Alan F Jorge R | 2005 | Am J Transplant2005，5，： | 1 |
| 14 | Erosion of Hard Material Coating Systems显示文摘 | Alan V Levy Bu QianWang | 1988 | Wear1988，121，： | 1 |
| 15 | Finite extinction time for solutions of nonlinear parabolic equations显示文摘 | ALAN V L | 1993 | Nonlinear Aanlysis1993，21，： | 1 |
| 16 | Structure and properties of poly (γ-benzyl-L-glutamate)cast from dimethylformamide显示文摘 | Alan J M Arthur V T | 1968 | The Journal of Physical Chemistry1968，72，4： | 1 |
| 17 | Assessment of stability of slopes under drawdown conditions显示文摘 | ALANE P GRIFFITHS D V | 2000 | Journal of G-eetechnical and Geoenvironmental Engineering2000，126，5： | 1 |
| 18 | A novel and effective particle swarm optimization like algorithm with extrapolation technique 显示文摘 | Senthil Arumugam M Rao M V C Tan Alan W C | 2009 | Applied Soft Computing2009，9，1： | 1 |
| 19 | The SKYLON spaceplane: pro- gress to realization显示文摘 | RICHARD V ALAN B | 2008 | JBIS2008，61，： | 1 |
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