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1.
二甲双胍自1957年上市以来,已在糖尿病的治疗领域中走过50余年历程,其临床应用价值也不断地被发掘.近年来,人们发现二甲双胍除了良好的降糖作用外还发挥着抗肿瘤效应,因此了解其在这方面的最新临床进展,探讨具体的抗肿瘤机制,对全面认识二甲双胍具有重要的意义. 相似文献
2.
Hypolipidemic effects of high-carbohydrate, high-fiber diets 总被引:2,自引:0,他引:2
Serial measurements of serum cholesterol and triglyceride (TG) concentrations were performed in diabetic men fed high-carbohydrate, high-fiber (HCF) as well as high-carbohydrate, low-fiber (HCLF) diets. Fourteen lean men were first fed control diets for 1 wk and then fed weight-maintaining HCF diets (70% carbohydrate) that were restricted in fat and cholesterol. Average insulin doses dropped from 27 U/day on control diets to 12 U/day on HCF diets and fasting plasma glucose values were 26 mg/dl lower on HCF diets. On HCF diets, serum cholesterol values were lower by 32% (64 mg/dl, p < 0.001) than values on control diets. Fasting serum TG values were slightly lower on HCF diets but average postprandial TG values were significantly lower (p < 0.001) on HCF diets than on control diets. In another study, 11 men were fed two weight-maintaining 70% carbohydrate diets in an alternating sequence; one diet was high in plant fiber (HCF) and the other was low in plant fiber (HCLF). Insulin doses averaged 20 U/day on control diets and fell to 11 U/day (p < 0.01) on HCF diets or 12 U/day (p < 0.01) on HCLF diets. Fasting serum TG values were similar on the control and HCF diets; on HCLF diets fasting serum TG values were higher by 28% (37 mg/dl) than values on control diets (p < 0.01). Incorporation of generous amounts of plant fiber into the diet prevented the hypertriglyceridemic response to these high-carbohdrate diets. These studies also indicate that dietary maneuvers can be very effective in lowering serum cholesterol values in patients with diabetes mellitus. 相似文献
3.
M. Lehtovirta B. Forsn M. Gullstrm M. Hggblom J. G. Eriksson M.‐R. Taskinen L. Groop 《Diabetic medicine》2001,18(7):578-583
AIMS: To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). METHODS: Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. RESULTS: Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 +/- 13 to 34.4 +/- 10.7 micromol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 +/- 3.6 to 19.1 +/- 4.4 micromol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. CONCLUSIONS: Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578-583 (2001) 相似文献
4.
Hypolipidemic effects of HMG-CoA reductase inhibitors in patients with hypercholesterolemia 总被引:2,自引:0,他引:2
Hypercholesterolemia with increased plasma concentrations of low density lipoproteins (LDL) is a major risk factor for the premature development of coronary atherosclerosis in humans and is best exemplified by patients with familial hypercholesterolemia. The recent development of several specific competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG CoA reductase) has opened up an important new avenue of therapy for patients with hypercholesterolemia who are not responsive to dietary treatment alone. Three drugs, lovastatin (mevinolin), simvastatin (synvinolin) and pravastatin (CS 514), are currently undergoing clinical trials in North America and Europe; the former has recently been approved for general use. Experience with lovastatin and simvastatin in the treatment of patients with primary and secondary causes of hypercholesterolemia is reviewed. The relative potency of simvastatin appears to be greater than that of lovastatin and pravastatin but, with each drug, decreases in the plasma concentrations of LDL cholesterol of 30% to 50% can be achieved. The hypocholesterolemic effects of HMG CoA reductase inhibitors can be potentiated by combination therapy with other approved lipid-lowering medications including the bile acid sequestrants and nicotinic acid. If long-term safety can be satisfactorily established, specific inhibitors of HMG CoA reductase represent a major advance in the therapy of hypercholesterolemia and afford the potential to reduce substantially the high incidence of premature atherosclerosis that occurs in patients with persistent hypercholesterolemia. 相似文献
5.
Eriksson A Attvall S Bonnier M Eriksson JW Rosander B Karlsson FA 《Diabetes, obesity & metabolism》2007,9(3):330-336
BACKGROUND: Although metformin is widely used in the management of type 2 diabetes, its mechanism(s) of action is not fully known, and there have been remarkably few reports on short-term effects of the drug. Here, we examined early effects on glucose and lipid metabolism, and on certain adipose tissue and inflammatory markers during treatment for 28 days. METHODS: Twenty-one patients were randomized to metformin (n = 16) or placebo (n = 5) and studied at baseline, 1, 2 and 4 weeks with blood sampling and oral glucose tolerance tests (OGTT). The active group received 500 mg metformin daily in week 1, 500 mg twice daily in week 2 and 1000 mg twice daily in week 3 and 4. RESULTS: After 7 days of treatment, a reduced area under curve (AUC) for glucose at OGTT with no change in AUC for insulin levels was observed compared with baseline. Insulin sensitivity, as derived from the OGTT by Gutt's index, was increased. Reductions in fasting plasma glucose, total and LDL-cholesterol appeared after 14 days, and reductions in triglycerides, plasminogen activator inhibitor-1 (PAI-1) and leptin after 28 days of treatment. There were no changes in body weight, adiponectin or C-reactive protein. Compared with placebo, the changes between day 0 and day 28 differed significantly with regard to AUC for glucose at OGTT and Gutt's index, and showed strong trends for PAI-1 and leptin. CONCLUSIONS: The data demonstrate that in type 2 diabetes metformin rapidly affects glucose handling without changing the concentrations of insulin. Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue. 相似文献
6.
Eriksson A Attvall S Bonnier M Eriksson JW Rosander B Karlsson FA 《Diabetes, obesity & metabolism》2007,9(4):483-489
BACKGROUND: Although metformin is widely used in the management of type 2 diabetes, its mechanism(s) of action is not fully known, and there have been remarkably few reports on short-term effects of the drug. Here, we examined the early effects on glucose and lipid metabolism and on certain adipose tissue and inflammatory markers during treatment for 28 days. METHODS: Twenty-one patients were randomized to metformin (n = 16) or placebo (n = 5) and studied at baseline, 1, 2 and 4 weeks with blood sampling and oral glucose tolerance tests (OGTT). The active group received 500 mg metformin daily in the first week, 500 mg twice daily during week 2 and 1000 mg twice daily during weeks 3 and 4. RESULTS: After 7 days of treatment, a reduced area under curve (AUC) for glucose at OGTT with no change in AUC for insulin levels was observed compared to baseline. Insulin sensitivity, as derived from the OGTT by Gutt's index, was increased. Reductions in fasting plasma glucose, total cholesterol and low-density lipoprotein cholesterol appeared after 14 days, and reductions in triglycerides, plasminogen activator inhibitor-1 (PAI-1) and leptin after 28 days of treatment. There were no changes in body weight, adiponectin or C-reactive protein. Compared with placebo, the changes between day 0 and day 28 differed significantly with regard to AUC for glucose at OGTT and Gutt's index, and showed strong trends for PAI-1 and leptin. CONCLUSIONS: The data demonstrate that in type 2 diabetes, metformin rapidly affects glucose handling without changing the concentrations of insulin. Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue. 相似文献
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E J Abbink P Pickkers A Jansen van Rosendaal J A Lutterman C J Tack F G M Russel P Smits 《Diabetic medicine》2002,19(2):136-143
AIMS: Glibenclamide attenuates the protective responses to opening of vascular ATP-sensitive potassium (K(ATP)) channels during ischaemia. Therefore, glibenclamide treatment of Type 2 diabetes mellitus may have hazardous cardiovascular effects when used under conditions of ischaemia. Glimepiride and metformin seem to lack such characteristics. Based on these data, we hypothesized that, in contrast to glibenclamide, chronic treatment of Type 2 diabetic patients with glimepiride or metformin will not impair the vasodilator function of K(ATP) opening in vivo. METHODS: Two groups of 12 Type 2 diabetes mellitus patients participated in a double-blind randomized cross-over study consisting of two 8-week periods, in which treatment with orally administered glibenclamide (15 mg/day) was compared with either glimepiride or metformin (6 mg and 1500 mg/day, respectively). At the end of each treatment period, the increase in forearm blood flow (FBF, venous occlusion plethysmography) in response to intra-arterial administered diazoxide (K(ATP) opener), acetylcholine (endothelium-dependent vasodilator) and dipyridamole (adenosine-uptake blocker) and to forearm ischaemia was measured. RESULTS: There were no significant differences in vasodilator responses to diazoxide, acetylcholine, dipyridamole and forearm ischaemia after glibenclamide compared with glimepiride and metformin. CONCLUSIONS: Chronic treatment of Type 2 diabetes mellitus with glimepiride or metformin has similar effects on vascular K(ATP) channels compared with chronic glibenclamide treatment. 相似文献
8.
二甲双胍对甲状腺功能的影响 总被引:2,自引:1,他引:1
二甲双胍作为一个经典的抗高血糖药物,在临床应用已走过了50余年的辉煌历史.近年来,有研究显示,二甲双胍对甲状腺功能减退症(甲减)患者的血清促甲状腺素(TSH)具有抑制作用,但不影响游离甲状腺素的水平,对于无甲状腺疾病的糖尿病患者的TSH水平亦无明显影响.推测可能与药物的相互作用、体重的改变、下丘脑-垂体-甲状腺轴的调节等因素有关,但尚缺乏令人信服的理论依据.虽然如此,这一意外的发现有可能对临床工作产生深远的影响,如二甲双胍有望作为甲状腺癌术后的辅助治疗措施. 相似文献
9.
近年的一些实验及临床观察表明,二甲双胍对糖尿病肾病有着独立于降糖作用之外的保护作用.相关机制可能包括抑制线粒体氧化呼吸链复合体Ⅰ,激活AMP活化蛋白激酶(AMPK),改善肾脏的氧化应激、炎性反应和高滤过状态,抑制晚期糖基化终末产物(AGEs)的生成,减轻肾脏脂质沉积以及肾小球硬化和间质纤维化等.对于合并肾脏并发症,估算的肾小球滤过率(eGFR)大于30 ml/(min·1.73m2)的糖尿病患者,可应用二甲双胍治疗. 相似文献
10.
Hypolipidemic effects of guar gum and its enzyme hydrolysate in rats fed highly saturated fat diets.
The effects of guar gum and its enzyme hydrolysate as well as fructooligosaccharide on lipid metabolism were compared in rats fed high-fat diets employing lard or palm oil as dietary fat (25% in the diets). Guar gum and the enzyme hydrolysate greatly increased cecal volatile fatty acid contents to a similar extent. Fructooligosaccharide also increased the variable but to a lesser extent. Not only guar gum but also the hydrolysate and the oligosaccharide reduced serum cholesterol levels irrespective of dietary fat sources but to a lesser extent. The triglyceride-lowering effects of the hydrolysate and the oligosaccharide were comparable to that of guar gum. Although guar gum enzyme hydrolysate and fructooligosaccharide doubled the biliary bile acid excretion, these materials only slightly increased the activities of hepatic enzymes of cholesterol and bile acid synthesis. Guar gum and its hydrolysate suppressed 3-hydroxy-3-methylglutaryl-coenzyme A reductase activities in the ileum to one half the control value in the experiment where dietary fat was lard. The highly polymeric structure does not appear to be a prerequisite for nonabsorbable carbohydrate to alter lipid metabolism at least in rats fed high-fat diets. 相似文献
11.
Joan P. Kay Ramin Alemzadeh G. Langley L. D''Angelo P. Smith S. Holshouser 《Metabolism: clinical and experimental》2001,50(12):1457-1461
Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals. It has been demonstrated that metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus (NIDDM) adults. To evaluate the antiobesity effect of metformin, we conducted a randomized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents (body mass index [BMI] >30 kg/m(2)). All subjects were placed on a low-calorie (1,500 kcal for women and 1,800 kcal for men) meal plan. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 15.6 +/- 0.4 and 41.2 +/- 1.8, respectively) received metformin (850 mg twice daily) for 8 weeks, and 12 subjects (mean +/- SE for age and BMI, 15.7 +/- 0.5 and 40.8 +/- 1.4, respectively) received placebo. Compared to the placebo group, the metformin group had greater weight loss (6.5% +/- 0.8% v 3.8 +/- 0.4%, P <.01), greater decrease in body fat (P <.001), greater increase in fat-free mass to body fat ratio (P <.005), and greater attenuation of area under the curve (AUC) insulin response to an oral glucose tolerance test (P <.001). This was associated with enhanced insulin sensitivity, as determined by the fasting plasma glucose:insulin, 2-hour glucose:insulin, and AUC glucose:AUC insulin ratios, in the metformin group compared to controls (P <.01). This corresponded to a significant reduction in plasma leptin (P <.005), cholesterol, triglycerides, and free fatty acid (FFA) levels (P <.05) only in the metformin-treated subjects. Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone. 相似文献
12.
迪化糖锭和降糖灵对Ⅱ型糖尿病降糖效果和副作用的临床观察 总被引:2,自引:0,他引:2
50例非胰岛素依赖型糖尿病随机交叉试验分为A、B两组,A组25例服迪化糖锭2个月后改子降糖灵,B组25例服降糖灵2个月后服迪化糖锭。总疗程4个月。 相似文献
13.
炎性反应在糖尿病肾病(DN)的发生、发展中起重要作用.高糖作为始动因素,与晚期糖基化终末产物(AGEs)、氧化应激及肾内血流动力学的改变共同引起了糖尿病肾脏炎性反应的发生.而二甲双胍作为治疗糖尿病的一线药物,近年研究显示其除降糖作用以外,还可通过激活腺苷酸活化蛋白激酶(AMPK)、抗氧化应激和改善胰岛素抵抗等机制发挥抗炎作用,从而预防和延缓DN的发生和发展. 相似文献
14.
S Parthasarathy D Kritchevsky W J Baumann 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(22):6890-6893
Clofibric acid (CPIB) and several other systemic hypolipidemic drugs are shown to block phosphatidylcholine synthesis by inhibiting cholinephosphotransferase (ChoPTase; CDPcholine:1,2-diacylglycerol cholinephosphotransferase, EC 2.7.8.2) and particularly lysolecithin acyltransferase (LLAcylTase; acyl-CoA:1-acylglycero-3-phosphocholine O-acyltransferase, EC 2.3.1.23) of rat liver microsomes. Whereas millimolar drug concentrations are required to affect de novo lecithin synthesis catalyzed by ChoPTase, reacylation of lysolecithin by LLAcylTase is inhibited at micromolar levels. Increasing effectiveness in ChoPTase inhibition is observed in the series CPIB, SaH-42-348, tibric acid, S-321328, WY-14643, S-8527, and DH-990, with IC50 ranging from 22 mM (CPIB) to 0.3 mM (DH-990). LLAcylTase inhibition by the hypolipidemic drugs follows the same general pattern, but IC50 concentrations range from 9 mM (CPIB) to 40 microM (DH-990). The agents inhibit ChoPTase (Ki, 25-0.25 mM) and LLAcylTase (Ki, 10-0.025 mM) noncompetitively. The data suggest that inhibition of phosphatidylcholine synthesis, particularly by the LLAcylTase pathway, may be related to a drug's effectiveness in decreasing serum triglyceride and cholesterol levels by blocking lipoprotein synthesis. 相似文献
15.
Aim: To investigate whether patients taking metformin for type 2 diabetes mellitus (T2DM) have improved glycaemic control without compromising tolerability by adding an agent with a complementary mechanism of action vs. uptitrating metformin. Methods: Adults with T2DM and glycated haemoglobin (HbA1c) between 7.0 and 10.5% receiving metformin extended release (XR) 1500 mg/day for ≥8 weeks were randomized to receive saxagliptin 5 mg added to metformin XR 1500 mg (n = 138) or metformin XR uptitrated to 2000 mg/day (n = 144). Endpoints were change from baseline to week 18 in HbA1c (primary), 120‐min postprandial glucose (PPG), fasting plasma glucose (FPG) and the proportion of patients achieving HbA1c <7%. Results: At week 18, the adjusted mean reduction from baseline HbA1c was ?0.88% for saxagliptin + metformin XR and ?0.35% for uptitrated metformin XR (difference, ?0.52%; p < 0.0001). For 120‐min PPG and FPG, differences in adjusted mean change from baseline between saxagliptin + metformin XR and uptitrated metformin XR were ?1.3 mmol/l (?23.32 mg/dl) (p = 0.0013) and ?0.73 mmol/l (?13.18 mg/dl) (p = 0.0030), respectively. More patients achieved HbA1c <7.0% with saxagliptin + metformin XR than with uptitrated metformin XR (37.2 vs. 26.1%; p = 0.0459). The proportions of patients experiencing any adverse events (AEs) were generally similar between groups; neither group showed any notable difference in hypoglycaemia or gastrointestinal AEs. Conclusion: Adding saxagliptin to metformin XR provided superior glycaemic control compared with uptitrating metformin XR without the emergence of additional safety concerns (Clinical Trials.gov registration: NCT00960076). 相似文献
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BACKGROUND. Elevated levels of cholesterol and apoprotein B (apo B), the essential carrier protein for low density lipoprotein, are major lipid risk factors for premature coronary disease. Antiarrhythmic agents are frequently prescribed to patients with coronary heart disease and associated cardiac arrhythmias. As part of another study, we retrospectively investigated the effect of antiarrhythmic agents on blood lipids. METHODS AND RESULTS. The study population consisted of 1,567 postinfarction patients on whom we prospectively collected serial blood samples for lipid and apoprotein determinations and recorded the concomitant medications the patients were receiving at three follow-up time periods. The lipids, analyzed at a central core laboratory, included total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL C), and apoproteins A-I (apo A-I), A-II (apo A-II), and apo B. The difference in the group mean lipid values for patients receiving and not receiving type Ia antiarrhythmic agents (quinidine, procainamide, and disopyramide) was evaluated by the two-sample t test, and multiple linear regression analyses were performed to adjust for relevant covariates. Patients using type Ia antiarrhythmic agents at the 30-month postinfarction contact (n = 76) had 8.6% lower cholesterol (p less than 0.003), 22.3% lower triglycerides (p less than 0.0002), 6.2% lower apo A-I (p = 0.02), 10.1% lower apo A-II (p less than 0.001), and 12.7% lower apo B (p less than 0.0001) levels than patients not on these medications (n = 1,491). These lower lipid levels were found after adjustment for age, sex, diabetes, smoking status, concomitant medications, and a variety of clinical factors relating to the severity of the coronary disease process. The HDL C levels were similar in those receiving and not receiving type Ia agents. CONCLUSIONS. Patients on type Ia antiarrhythmic agents had significantly and meaningfully lower cholesterol, triglyceride, apo A-II, and apo B levels than patients not receiving these agents. The mechanism of this hypolipidemic effect is undefined, but the mechanism may be related to an alteration by these agents of ionic membrane currents at the hepatocyte level. 相似文献
18.
二甲双胍新降糖机制及其降糖以外作用 总被引:1,自引:0,他引:1
二甲双胍的应用已有50年历史.近年对其降糖机制的进一步研究发现,其能通过抑制二肽基肽酶Ⅳ(DPPⅣ)活性、增强胰升糖素样肽-1(GLP-1)的生物学效应而达到降低血糖的目的.此外,二甲双胍还具有改善胰岛素抵抗、降低总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)的效应,并能降低凝血因子Ⅶ、纤溶酶原激活剂抑制因子-1(PAI-1)及减少蛋白尿的作用,有益于降低2型糖尿病患者血管病变的风险.虽然二甲双胍对糖尿病患者血压改变不明显,但是对盐敏感的肥胖患者血压有显著的降低.二甲双胍还能够应用于多囊卵巢综合征(PCOS)的治疗,诱发排卵、降低流产率,对多毛和高雄激素血症也有一定的治疗效果.此外,二甲双胍在非酒精性脂肪性肝病治疗领域也成为关注的热点. 相似文献
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二甲双胍干预大鼠非酒精性脂肪性肝炎疗效观察 总被引:3,自引:1,他引:2
目的观察二甲双胍对非酒精性脂肪性肝炎大鼠模型的干预作用。方法实验动物分3组,模型组和治疗组各12只雄性SD大鼠给予高脂肪高胆固醇饲料喂养,另设6只普通饲料喂养大鼠作为对照组。治疗组从高脂饮食第4周起在饮水中加用二甲双胍(每天250mgkg)。所有大鼠均于实验24周后处死,进行血清生化和肝脏组织学检测。结果与模型组相比,治疗组肝脏指数和腹腔脂肪含量显著减少(P均<0.001),且体重呈下降趋势;血清天冬氨酸转氨酶[(162.45±11.2)UL比(115.9±29.3)UL,P=0.01]、三酰甘油(1.10±0.24比0.75±0.30,P=0.01)水平显著下降;治疗组肝脏组织学炎症评分(1.20±1.14比4.83±1.05,P<0.01)和肝纤维化评分(0.70±0.48比1.42±0.45,P<0.05)显著下降,伴肝脂肪变程度减轻(P<0.05)。结论二甲双胍早期干预可显著改善高脂饮食大鼠脂肪性肝炎和纤维化程度,伴肝重、腹部脂肪含量及血清三酰甘油水平下降。 相似文献