二甲双胍联合治疗临床疗效的研究进展

二甲双胍作为T2DM患者的一线用药已被广泛共识,但T2DM是一种进行性疾病,起始采用二甲双胍单药治疗的患者,随时间的推移和病程的进展,常需联合其他口服降糖药物,如磺脲类、格列奈类、TZDs、α-葡萄糖苷酶抑制剂(AGDI)、二肽基肽酶-4(DPP-4)抑制剂、胰升血糖素样肽-1(GLP-1)受体激动剂或胰岛素制剂来控制血糖。本文就二甲双胍与其他降糖药物联用的临床疗效研究进展作一综述。     

Aspirin in a diabetic retinopathy setting: Insights from NO BLIND study

Background and aimsDiabetic retinopathy (DR) is the most common microvascular complication of diabetes. Diabetic macroangiopathies, particularly cardiovascular (CV) diseases, seem closely related to diabetes microvascular complications. Aspirin represents the most prescribed compound in CV prevention. Aspirin impact on DR is still object of debate. As it is already recommended among diabetics at high CV risk, aim of this study was to assess a potential relationship between DR and aspirin therapy, in a type 2 diabetes cohort of patients screened through telemedicine.Methods and resultsNO Blind is a cross-sectional, multicenter, observational study, which involved nine Italian outpatient clinics. Primary endpoint was the assessment of the relationship between aspirin treatment and DR. 2068 patients were enrolled in the study, subsequently split in two subpopulations according to either the presence or absence of DR. Overall, 995 subjects were under aspirin therapy. After adjusting for most common potential confounders, age and gender, aspirin reveals significantly associated with DR (OR: 1.72, 95%CI: 1.58–2.89, p = 0.002) and proliferative DR (PDR) (OR: 1.89, 95%CI: 1.24–2.84, p = 0.003). Association comes lost further adjusting for MACEs (OR: 1.28, 95%CI: 0.85–1.42, p = 0.157) (Model 4) and eGFR (OR: 0.93; 95%CI: 0.71–1.22; p = 0.591) (Model 5).ConclusionIn this multicenter cross-sectional study including a large sample of outpatients with T2DM, we showed that aspirin was not associated with DR after adjustment for several cardio-metabolic confounders. However, as partially confirmed by our findings, and related to the well-known pro-hemorrhagic effect of aspirin, its use should be individually tailored, even by telemedicine tools.     

Automated Continuous Electrocardiogram Monitoring Accelerates the Detection of Atrial Fibrillation after Ischemic Stroke or Transient Ischemic Attack on a Hyper Acute Stroke Unit

Background and Aim: Rapid and sensitive detection of atrial fibrillation (AF) is of paramount importance for initiation of adequate preventive therapy after stroke. Stroke Unit care includes continuous electrocardiogram monitoring (CEM) but the optimal exploitation of the recorded ECG traces is controversial. In this retrospective single-center study, we investigated whether an automated analysis of continuous electrocardiogram monitoring (ACEM), based on a software algorithm, accelerates the detection of AF in patients admitted to our Stroke Unit compared to the routine CEM. Methods: Patients with acute ischemic stroke or transient ischemic attack were consecutively enrolled. After a 12-channel ECG on admission, all patients received CEM. Additionally, in the second phase of the study the CEM traces of the patients underwent ACEM analysis using a software algorithm for AF detection. Patients with history of AF or with AF on the admission ECG were excluded. Results: The CEM (n = 208) and ACEM cohorts (n= 114) did not differ significantly regarding risk factors, duration of monitoring and length of admission. We found a higher rate of newly-detected AF in the ACEM cohort compared to the CEM cohort (15.8% versus 10.1%, P < .001). Median time to first detection of AF was shorter in the ACEM compared to the CEM cohort [10 hours (IQR 0–23) versus 46.50 hours (IQR 0–108.25), P < .001]. Conclusions: ACEM accelerates the detection of AF in patients with stroke compared with the routine CEM. Further evidences are required to confirm the increased rate of AF detected using ACEM.     

血清胱抑素-C水平与糖尿病足溃疡严重程度的关系研究

目的 探讨血清高胱抑素-C水平与糖尿病足溃疡（DFU）严重程度是否存在联系。方法 本研究为横断面研究,纳入上海市糖尿病临床医学中心2014年1月～2015年2月就医的975例2型糖尿病（T2DM）患者,其中足溃疡（DFU）患者110例,865例无足病者（NDF）作为对照组。收录患者血清、一般临床数据、糖代谢指标、血脂、肝肾功能、胱抑素C、C反应蛋白、血常规等生化指标检测结果。采取t检验、方差分析、卡方检验、Spearman相关分析、多元Logistic回归分析等统计学方法研究Cys C与DFU严重程度的关系。结果 DF组年龄、病程、吸烟比例、空腹血糖、血肌酐、血清CysC、糖化血红蛋白水平均明显高于非足病组（NDF）,差异有统计学意义（P均<0.01）。DFU患者不同Wagner水平间单因素方差分析显示,DFU患者的Wagner分级越高,Cys C升高越明显（F=11.27,P<0.01）;且血肌酐、尿素氮、糖化血红蛋白水平越高（F=4.9、4.9、3.18,P均<0.05）。Spearman相关分析表明,ABI水平与DFU的Wagner分级呈负相关（r=-0.241,P<0.05）,吸烟史、Cys C、肌酐、尿酸、糖化血红蛋白水平与DFU患者的Wagner分级呈正相关（r=0.205、0.344、0.237、0.231、0.053,P均<0.05）。Logistic回归分析显示,排除其他DFU严重程度的传统影响因子后,Cys C升高仍是DFU Wagner分级级别的独立影响因素（β=1.381,95%CI：1.039～15.228,P<0.01）。结论 血清胱抑素-C水平与糖尿病足溃疡密切相关,高胱抑素-C水平提示糖尿病足溃疡更严重。     

14-3-3β蛋白介导胰高血糖素作用下糖异生的特点及机制

目的 分别观察胰高血糖素在空质粒转染组和14-3-3β蛋白过表达组对HepG2细胞糖异生的影响,并对14-3-3β蛋白介导此现象出现的可能原因初步探讨。方法 对转染空质粒或14-3-3β质粒低糖培养基培养的HepG2细胞分别在有无胰高血糖素作用下,进行培养基中葡萄糖产量的测定并观察糖异生关键酶蛋白表达量的变化;用免疫共沉淀的方法判定稳定转染胰高血糖素受体的293细胞在胰高血糖素对待下,14-3-3β蛋白与胰高血糖素受体结合的变化。结果 在未加及加入胰高血糖素对待下,14-3-3β转染组与空质粒对照组相比葡萄糖产量降低（P均<0.05）;糖异生关键酶表达量降低（P均<0.05）;免疫共沉淀显示胰高血糖素受体、14-3-3β蛋白与碳水化合物反应元件三者处于结合状态,且在胰高血糖素作用下14-3-3β蛋白与胰高血糖素受体结合减少而与碳水化合物反应元件结合增多（P均<0.05）。结论 过表达14-3-3β蛋白可起到抑制胰高血糖素的糖异生作用且这种现象发生的原因可能与其同碳水化合物反应元件间的相互作用及产生的后续效应有关。