阿卡波糖联合二甲双胍治疗初诊2型糖尿病患者疗效观察

目的:探讨阿卡波糖及二甲双胍单独或联合应用治疗初诊2型糖尿病患者的临床效果.方法:选择63例初诊2型糖尿病患者,进行运动和饮食治疗的基础上,分别给予阿卡波糖(50mg,tid),二甲双胍(0.5g,tid)或两药联合治疗6个月,比较治疗前后所有患者的空腹血糖(FBS)、餐后血糖(PBS)、空腹胰岛素(FINS)、餐后胰...     

二甲双胍对多囊卵巢综合征患者体外受精-胚胎移植影响的初步研究

目的探讨二甲双胍预处理对多囊卵巢综合征（PCOS）患者体外受精-胚胎移植（IVF-ET）的影响。方法随机将60名PCOS患者分为二甲双胍组和对照组,接受3个月预处理,然后开始IVF-ET治疗。对比分析两组患者的一般情况、代谢水平、超排卵过程、胚胎情况及妊娠结局。结果两组人群在预处理前后的代谢水平、胰岛素敏感性变化无显著差异（P〉0.05）。二甲双胍组的Gn使用剂量及天数、HCG日E2水平、内膜厚度均与对照组相似（P〉0.05）;而获卵数（8.90±8.94）、成熟卵数（8.20±8.43）、受精胚胎数（6.80±6.22）均显著小于对照组（14.92±5.25,14.08±5.40,13.67±5.26,P〈0.05）。二甲双胍组的优质胚胎率稍高于对照组（44.12%比32.32%）,但差异不明显（P〉0.05）。两组间临床妊娠率无显著差异（P〉0.05）,二甲双胍组早期流产率稍低（20%比50%）,但差异不显著（P〉0.05）。结论 PCOS患者在开始IVF-ET治疗前服用3个月的二甲双胍并不能有效改善超排卵情况和妊娠结局,但可能对防止流产有一定作用。     

CORE糖尿病模型预测利拉鲁肽联合二甲双胍治疗2型糖尿病的长期健康结果

目的预测利拉鲁肽联用二甲双胍治疗2型糖尿病的长期健康结果。方法临床数据来源于国际多中心随机对照双盲临床试验NCT00614120,入组对象为来自中国、印度和韩国的2型糖尿病患者。选取利拉鲁肽1.2 mg·d~(-1)组(n=233)、利拉鲁肽1.8 mg·d~(-1)组(n=234)和格列美脲4.0 mg·d~(-1)组(n=231)的患者作为研究对象,每组患者均联用二甲双胍1.5～2.0 g·d~(-1),3组完成试验分别为187例、175例和215例。应用CORE糖尿病模型,输入16 wk临床试验前后患者机体参数改变值,模拟患者终身(30年)治疗健康结果。结果与格列美脲4.0 mg·d~(-1)组相比,利拉鲁肽1.2 mg·d~(-1)组患者背景型视网膜病变、终末期肾病、首次足溃疡和充血性心力衰竭死亡的累积发病率分别降低0.195%、0.086%、0.020%和0.528%,存活率增加了0.32%,预期寿命增加0.018年,质量调整生命年增加0.11年;利拉鲁肽1.8 mg·d~(-1)组以上4种并发症的累积发病率分别降低0.607%、0.116%、0.337%和0.626%,存活率增加了0.42%,预期寿命增加0.051年,质量调整生命年增加0.108年。敏感度分析结果显示,当模拟时间跨度分别设为10年、20年、35年,贴现率分别设置为0和5%时,与格列美脲4.0 mg·d~(-1)组的模拟结果相比,利拉鲁肽1.2 mg·d~(-1)组和1.8 mg·d~(-1)组均获得较长的存活率、预期寿命和质量调整生命年。结论与格列美脲联用二甲双胍相比,利拉鲁肽联用二甲双胍能够延缓并减少2型糖尿病患者并发症的发生,增加存活率、预期寿命与质量调整生命年。     

Feasibility of Intermittent Hemodialysis in Metformin Toxicity With Shock

BackgroundMetformin toxicity can lead to profound shock and has a high mortality rate. Supportive care and enhanced elimination are the mainstays of therapy. Intermittent hemodialysis (HD) produces a higher clearance of metformin than continuous veno-venous hemofiltration or hemodiafiltration (CVVH/HDF). Nevertheless, CVVH/HDF has been proposed as an alternative in critically ill patients with the suggestion that hypotension may limit the use of HD.ObjectiveThis study sought to analyze the feasibility of performing hemodialysis in patients with persistent shock from metformin toxicity.MethodsWe performed a 6-year (2012–2017) retrospective chart review of patients with metformin toxicity managed at a large academic institution with a toxicology service. We included patients with persistent shock on vasopressor support who were treated with HD. Baseline characteristics, complications from treatment, timing of dialysis, and differences between mean arterial pressures before, during, and at the end of dialysis were recorded and analyzed.ResultsDespite critical mean peak lactate (23.9 mMol/L [range 17.6–27.9]), pH (6.91 [range 6.78–7.01]), and metformin levels (range 25–58 μg/mL], 6 of 7 patients recovered. All patients required prolonged HD (mean 19 h). Upon completion of HD, hemodynamics had improved (45 mm Hg [95% confidence interval 35–55 mm Hg] vs. 80 mm Hg [95% confidence interval 74–86 mm Hg]) and vasopressor support decreased. Mortality in this patient cohort was 14.3% (1/7).ConclusionIntermittent HD is feasible in metformin toxicity despite persistent shock and high-dose vasopressor support. Mean arterial pressures improved during the course of HD and high blood flow rates were tolerated.     

二甲双胍对2型糖尿病合并亚临床甲状腺功能异常患者的影响

目的评价二甲双胍对2型糖尿病合并亚临床甲状腺功能异常患者的影响。方法选择2型糖尿病合并亚临床甲状腺功能异常患者81例,按亚临床甲状腺功能减退或亢进分为两组,给予二甲双胍片3次/d,每次0.25 g,观察其对两组患者治疗后血清促甲状腺素含量的影响。结果 81例患者治疗后血糖降低,治疗前后血糖值比较,差异有统计学意义(P<0.05);两组患者的TT3和TT4治疗前后比较差异均无统计学意义(P>0.05);亚临床甲状腺功能亢进组治疗后TSH值降低,治疗前后比较差异有统计学意义(P<0.05)。结论二甲双胍可降低2型糖尿病合并亚临床甲状腺功能异常患者血清促甲状腺素含量,其在治疗2型糖尿病的同时对甲状腺功能无损害。     

High Recovery of Functional Islets Stored at Low and Ultralow Temperatures

BACKGROUND: Poor recovery of islets upon cryopreservation is the main hurdle in islet banking. Pancreatic islets have a poor antioxidative defense mechanism, and exposure of islets to low temperature leads to oxidative stress. AIM: We aimed to investigate whether known compounds such as metformin, γ aminobutyric acid (GABA), docosahexanoic acid (DHA), or eicosapentaenoic acid (EPA) alone or in combination are capable of reducing oxidative stress for better islet recovery upon storage at suboptimal temperatures. METHODS: Islets isolated from mouse pancreas were stored at low temperature (4°C) for 15 days and at ultralow temperature (-196°C) for 30 days with or without additives. After revival from cold storage, islets were assessed by using three methods: (1) specificity by dithizone (DTZ), (2) viability by fluorescein diacetate/propidium iodide (FDA/PI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) assay, and (3) functionality by glucose-stimulated insulin secretion (GSIS). The oxidative status of the islets stored at suboptimal temperatures was determined by both intracellular free radical release (fluorometric analysis) and lipid peroxidation (enzymatic determination). RESULTS: Supplementation with additives led to an improvement in islet survival upon storage at suboptimal temperatures, without depletion of insulin secretory activity, which was comparable to that of controls. The additives acted as cryoprotectants and antioxidants as revealed by high recovery of viable islets and reduction in total reactive oxygen species (ROS) and malonidealdehyde (MDA), respectively. CONCLUSIONS: Our results demonstrate for the first time that supplementation with EPA, DHA, and metformin may lead to higher islet recovery from -196°C storage, enabling proper islet banking.     

Elevated GLUT 1 level in crude muscle membranes from diabetic Zucker rats despite a normal GLUT 1 level in perineurial sheaths

Summary Recently, we demonstrated that approximately 60 % of GLUT 1 in a crude membrane fraction of rat skeletal muscle originates from perineurial sheaths. To study the in vivo regulation of GLUT 1 expression in different tissues in muscles, we measured the level of GLUT 1 in crude muscle membranes and in perineurial sheaths in diabetic (fa/fa) Zucker rats and lean controls, with and without metformin treatment. The GLUT 1 concentration in perineurial sheaths was identical in all four groups of rats, both when measured by quantitative immunofluorescence and by immunoblotting and densitometry. In a fraction of crude membranes of soleus muscles GLUT 1 expression was more than two-fold higher in (fa/fa) rats than in lean controls (p<0.005). Metformin treatment significantly elevated GLUT 1 in control rats (p<0.05) and tended to decrease GLUT 1 in diabetic rats (p<0.075). The expressions of GLUT 1 and GLUT 4 in crude muscle membranes were inversely correlated (p<0.01), and GLUT 1 expression correlated positively with fasting glucose (p<0.05). In conclusion, GLUT 1 expression in perineurial sheaths is unaffected by alterations in glucose homeostasis and by the genes responsible for obesity and diabetes in the Zucker rat. GLUT 1 expression in a crude membrane fraction of soleus muscle is increased in the diabetic animals, likely due to an increased expression in muscle cells proper. [Diabetologia (1994) 37: 443–448] Received: 17 June 1993 and in revised form: 19 November 1993     

Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes.

AIM: Metformin therapy reduces microvascular complications in Type 2 diabetes; questions remain, however, regarding its impact on macrovascular events. This study examined metformin use in relation to risk of cardiovascular-related hospitalization and mortality. METHODS: We conducted a retrospective cohort analysis, using Saskatchewan Health administrative databases to identify new users of oral antidiabetic drugs. Subject groups were defined by medication use during 1991-1999: sulphonylurea monotherapy, metformin monotherapy, or combination therapy. Deaths and non-fatal hospitalizations recorded during the study period were identified as cardiovascular-related from ICD-9 codes. The main outcome was a composite of first non-fatal hospitalization or death. Standard multivariate techniques, including propensity scores, were used to adjust for potential confounding. Multivariate Cox proportional hazard models were used to examine the relationship between metformin use and the composite endpoint. RESULTS: Metformin monotherapy was associated with a lower risk of the composite endpoint (adjusted hazard ratio 0.81; 95% confidence interval 0.68, 0.97) compared with sulphonylurea monotherapy. Combination therapy with meformin and a sulphonylurea was associated with lower mortality, but had similar hospitalization rates, to sulphonylurea monotherapy. CONCLUSIONS: Metformin monotherapy was associated with a lower risk of cardiovascular-related morbidity and mortality, and combination metformin and sulphonylurea therapy was associated with a reduced risk of fatal cardiovascular events, when compared with sulphonylurea monotherapy.