还原型谷胱甘肽联合二甲双胍治疗2型糖尿病并发脂肪肝疗效观察

①目的探讨还原型谷胱甘肽(GSH)联合二甲双胍(m etform in)治疗糖尿病并发脂肪肝的疗效。②方法48例糖尿病并发脂肪肝患者,均在运动与饮食治疗基础上,常规护肝治疗;用还原型谷胱甘肽1 200mg,加入5%葡萄糖注射液250mL中,每日1次,静脉滴注,每次口服二甲双胍片0.25g,每日3次。3个月为一疗程,观察有关指标及B超影像学改变。③结果经治疗后患者丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、谷氨酰转肽酶(GGT)降至正常(P<0.001),血总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及体重指数(BM I)值较治疗前显著降低(P<0.001),空腹血糖(FPG)、糖化血红蛋白(HbA1 c)较治疗前下降(P<0.001),计算比较稳态模式胰岛素抵抗指数(HOMA-IR)和稳态模式胰岛素敏感指数(HOMA-IAI)值,差异具有显著性意义(P<0.005)。④结论对伴有脂肪肝的2型糖尿病患者应用还原型谷胱甘肽联合二甲双胍治疗,能有效地改善胰岛素抵抗,提高胰岛素敏感性,具有降酶、降糖、调脂的功效,疗效较好。     

Cardiovascular effects of anti-diabetes drugs

ABSTRACT

Introduction: Cardiovascular disease remains the major contributor to morbidity and mortality in diabetes. From the need to reduce cardiovascular risk in diabetes and to ensure that such risk is not exacerbated by drug treatments, governmental regulators and drug manufacturers have focused on clinical trials evaluating cardiovascular outcomes.

Areas covered: Findings from mechanistic and clinical trials of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors will be reviewed. These drug classes will be compared within the context of available cardiovascular outcomes data. Clinical implications of new study regulations will be examined.

Expert opinion: Recent cardiovascular studies provide a more comprehensive evaluation of specific anti-diabetes therapy in individuals with high cardiovascular risk. Long-term effects of anti-hyperglycemic agents in patients with lower cardiovascular risk are still speculative. Historical data supports continued use of metformin as a first-line agent. DPP-4 inhibitors and GLP-1 receptor agonists appear to have neutral effects on cardiovascular outcomes. The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin.     

Do antidiabetic medications play a specific role in differentiated thyroid cancer compared to other cancer types?

The risk for differentiated thyroid cancer, like for many other types of cancer, is increased in obese individuals and people with intermediate hyperglycaemia. The incidence of all cancers, with the exception of thyroid cancer, is also increased in type 2 diabetes mellitus patients. The review compares the prevalence of thyroid carcinoma and other cancers in obese, people with intermediate hyperglycaemia and patients with diabetes and summarizes mode of action and anti-tumourigenic effect of common antidiabetic medications. The over-expression of dipeptidyl peptidase IV in the tumours, not seen in the other cancer types, is suggested as a potential reason for the unique situation in thyroid cancer.     

Metformin-associated lactic acidosis: a rare or very rare clinical entity?

AIMS: Lactic acidosis is a well recognized complication of biguanide therapy which is potentially serious. Although the prevalence of metformin-associated lactic acidosis (MALA) is much lower than that associated with phenformin, it is still being reported sporadically which raises concerns for the practising clinicians. We review the currently available world-wide data of the prevalence of MALA, the risk factors for its development and the current practical guidelines on the use of metformin to minimize the risk of this potential hazard. METHODS: An extensive literature search was conducted from both Medline and Ovid (1965-98) using the following keywords: 'Type 2 diabetes mellitus', 'oral hypoglycaemic drugs', 'biguanides', 'metformin-associated lactic acidosis' and 'renal impairment'. RESULTS: MALA was found to be a very rare clinical entity, being 20 times less common than phenformin-associated lactic acidosis. Amongst all the risk factors, renal impairment appears to be the major precipitating factor for the development of MALA in metformin-treated patients. We also found cases of MALA where no precipitating factors were identified and the underlying mechanism in these cases remains unclear. Practical recommendations of metformin use to minimize the risk of MALA have been listed based on previous reports. CONCLUSIONS: The low prevalence of MALA is comparable to the prevalence of sulphonylurea-induced hypoglycaemia. Metformin has many beneficial metabolic effects in the management of Type 2 diabetes mellitus. Provided that the recommended guidelines for metformin use are strictly adhered to, its widespread use would be safe and the incidence of MALA will be further reduced.     

三种方法去除残留消毒剂的效果观察

目的观察三种残余消毒剂去除方法在应用中可能会出现的问题,以求更准确地评价化学消毒剂杀菌效果。方法采用载体定量杀菌试验方法,对化学中和法、稀释法和中和过滤冲洗法等三种方法对抑菌作用较强的胍类消毒剂去除效果进行了评价。结果用5g/L组氨酸、3g/L卵磷脂和30g/L吐温80组成的中和剂,用化学中和法对含50g/L双胍类消毒液中残留作用去除不彻底,各组长菌数不符合中和剂试验要求;但对含5g/L双胍类消毒剂的残留作用可达到有效去除效果。相同的中和剂用中和稀释法,对含50g/L和5g/L两种浓度的胍类消毒剂残留毒性均可达到有效去除效果。用中和过滤冲洗法不能有效去除含量50g/L的胍类消毒液残余作用,但可有效去除含量为5g/L胍类消毒液对试验菌的残留作用。用上述复方中和剂进行杀菌效果评价验证试验,以含50g/L双胍类消毒液对载体上枯草杆菌黑色变种芽孢作用60min,用化学中和法与过滤冲洗去除残余消毒剂,消毒后检不出存活细菌;而用中和稀释法去除残余消毒剂方法消毒后存活菌数为189000cfu/片,平均杀灭率为91.54%。用含5g/L双胍类消毒液对载体上该细菌芽孢作用60min,三种去除残余消毒剂的方法检验出的消毒后存活菌数基本一致,平均杀灭率完全一致。结论三种去除残余消毒剂的方法中,以中和稀释法效果最好,可用于高浓度抑菌作用较强的消毒剂杀菌效果评价。     

Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes

Aim: To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment‐naïve patients with type 2 diabetes. Methods: In a double‐blind study, 1050 treatment‐naïve patients (i.e. not taking an antihyperglycaemic agent for ≥16 weeks prior to study entry) with type 2 diabetes and an HbA_1c 6.5–9% were randomized (1:1) to treatment with once‐daily sitagliptin 100 mg (N = 528) or twice‐daily metformin 1000 mg (N = 522) for 24 weeks. Metformin was up‐titrated from 500 to 2000 mg per day (or maximum tolerated daily dose ≥1000 mg) over a period of 5 weeks. The primary analysis used a per‐protocol (PP) approach to assess whether sitagliptin was non‐inferior to metformin based on HbA_1c change from baseline at week 24. Non‐inferiority was to be declared if the upper boundary of the 95% confidence interval (CI) for the between‐group difference in this endpoint was <0.40%. Results: From a mean baseline HbA_1c of 7.2% in the PP population, HbA_1c change from baseline was ?0.43% with sitagliptin (n = 455) and ?0.57% with metformin (n = 439). The between‐group difference (95% CI) was 0.14% (0.06, 0.21), thus confirming non‐inferiority. Baseline HbA_1c influenced treatment response, with larger reductions in HbA_1c observed in patients with baseline HbA_1c≥8% in the sitagliptin (–1.13%; n = 74) and metformin (–1.24%; n = 73) groups. The proportions of patients at week 24 with HbA_1c values at the goals of <7 or <6.5% were 69 and 34% with sitagliptin and 76 and 39% with metformin, respectively. Fasting plasma glucose changes from baseline were ?11.5 mg/dL (–0.6 mmol/l) and ?19.4 mg/dl (–1.1 mmol/l) with sitagliptin and metformin, respectively (difference in LS mean change from baseline [95% CI] = 8.0 mg /dl [4.5,11.4]). Both treatments led to similar improvements from baseline in measures of homeostasis model assessment‐β cell function (HOMA‐β) and insulin resistance (HOMA‐IR). The incidence of hypoglycaemia was 1.7% with sitagliptin and 3.3% with metformin (p = 0.116). The incidence of gastrointestinal‐related adverse experiences was substantially lower with sitagliptin (11.6%) compared with metformin (20.7%) (difference in incidence [95% CI] = ?9.1% [?13.6,?4.7]), primarily because of significantly decreased incidences of diarrhoea (3.6 vs. 10.9%; p < 0.001) and nausea (1.1 vs. 3.1%; p = 0.032). Body weight was reduced from baseline with both sitagliptin (LS mean change [95% CI] = ?0.6 kg [?0.9,?0.4]) and metformin (–1.9 kg [–2.2, ?1.7]) (p < 0.001 for sitagliptin vs. metformin). Conclusions: In this 24‐week monotherapy study, sitagliptin was non‐inferior to metformin in improving HbA_1c in treatment‐naïve patients with type 2 diabetes. Although both treatments were generally well tolerated, a lower incidence of gastrointestinal‐related adverse experiences was observed with sitagliptin.     

Biguanide-induced lactic acidosis in Finland

Summary Twenty-four patients with biguanide-induced lactic acidosis were reported to the Adverse Drug Reaction Register of the Finnish National Board of Health from 1974–1977. Of them, 23 had been treated with phenformin and one with metformin. The mean age of the patients was 71 years, and all but one were more than 65 years of age. The mortality rate was 63%. One patient had cirrhosis of the liver and one was already known to have had impaired renal function. Fourteen of the patients had a normal serum creatinine concentration either before or after the development of lactic acidosis. Thus, in most patients it had not been possible to prevent development of lactic acidosis by observing the contraindications to biguanide therapy. Most patients had some form of co-existing cardiovascular disease. Tetracycline therapy was a probable precipitating factor in three cases. Based on the statistics of biguanide consumption in Finland, the annual incidence of biguanide-induced lactic acidosis in 1976 and 1977 was between 1/2000 and 1/3000 and that of fatal lactic acidosis was 1/4000.     

Effect of phenformin on lipid and carbohydrate metabolism in pregnant rats

A decrease in the blood levels of cholestrol, phospholipids, and free fatty acids was observed in rats receiving the biguanide phenformin (5–25 mg daily by mouth) from the first to eighth day of pregnancy, but no developmental anomalies of the fetuses or placenta were found. The acceptability of biguanide administration during pregnancy is discussed.Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Serebrov.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 825–827, July, 1976.     

盐酸二甲双胍致不良反应1例

糖尿病是一种常见病及多发病,往往需要终身治疗,随着糖尿病发病率的不断上升,占糖尿病患者总数90%以上的2型糖尿病患者,治疗方案较多,在药物选择原则上,除了安全性和有效性外,盐酸二甲双胍是治疗糖尿病药物中最经济的品种之一,盐酸二甲双胍不仅能降血糖,且有调节血脂、改变患者对胰岛素敏感性等作用,药物不经肝脏代谢,以原型经尿排出体外,在体内易消除,且能保护心血管免受损害,而且不会引起低血糖.因此,盐酸二甲双胍是治疗2型糖尿病的良好药物.盐酸二甲双胍（Metformin hydrochloride,MFH）是双胍类抗糖尿病药,为目前治疗Ⅱ型糖尿病的首选药物.MFH在胃肠道的吸收不完全,主要吸收部位在小肠.     

复方中和剂对隐形眼镜护理液中和效果观察

目的观察复方中和剂对隐形眼镜护理液中和效果。方法采用悬液定量杀菌试验程序,对由硫代硫酸钠、卵磷脂、吐温组成的复方中和剂中和含有双胍类杀菌成分的隐形眼镜护理液的效果进行了检测。结果用含5g/L硫代硫酸钠、5 g/L卵磷脂、10 g/L吐温80组成的复方中和剂可有效中和含双胍类和表面活性剂的隐形眼镜护理液的残留作用,中和剂鉴定试验结果符合规范规定的技术指标。结论鉴定试验证明,该复方中和剂可用于含双胍类杀菌成分的隐形眼镜护理液杀菌试验。