罗格列酮和二甲双胍对高脂饲养造成的胰岛素抵抗的影响

目的　观察高脂饲养正常大鼠造成胰岛素抵抗 (IR)及不同药物干预的影响。方法将 8周龄雄性SD大鼠随机分为 4组 ,每组各 11只 :正常饲养组 (NC)、高脂饲养组 (HF)、高脂 二甲双胍组 (HF Met)、高脂 罗格列酮组 (HF Ros)。罗格列酮 3mg·kg-1·d-1或二甲双胍 30 0mg·kg-1·d-1剂量进行灌胃。饲养 8周时取空腹血测游离脂肪酸 (FFA)、甘油三酯 (TG)、脂联素等。胰岛素敏感性用正常血糖高胰岛素钳夹技术稳态时的葡萄糖输注率 (GIR)来评价。结果　高脂饲养 8周后 ,与NC组相比 ,HF组呈现肥胖 ,血浆脂联素水平低 4 3 7% (P <0 0 1) ,GIR低 5 1 3% (P <0 0 1)。HF Met组体重和TG均低于HF组 ,分别低 8 4 %和 4 0 5 % ,P值均 <0 0 1,GIR高5 8 9% (P <0 0 1)。HF Ros组FFA和TG均显著低于HF组 ,分别低 2 5 3% (P <0 0 5 )和 5 4 0 %(P <0 0 1) ,血浆脂联素水平高 6 0 % (P <0 0 1) ,GIR高 14 9 6 % (P <0 0 1)。结论　 (1)正常热量高脂饲养正常SD大鼠 8周可引起肥胖 ,血浆脂联素水平下降和胰岛素抵抗。 (2 )罗格列酮和二甲双胍均可显著改善高脂饲养引发的胰岛素抵抗。前者伴有显著血FFA、TG降低和脂联素升高 ,后者伴有体重及血TG降低。     

罗格列酮和二甲双胍治疗多囊卵巢综合征随机对照研究

将40例多囊卵巢综合征(PCOS)患者随机分为两组,A组口服二甲双胍联合克罗米芬治疗,B组口服罗格列酮联合克罗米芬治疗,两组用药时间均为3个月经周期,比较用药后血脂、血糖、胰岛素、胰岛素抵抗指数、睾酮、瘦素、脂联素、BMI等指标变化和排卵率的改善情况.结果 提示罗格列酮比二甲双胍能更好地降低PCOS患者的胰岛素抵抗,提高促排卵率,但对血糖、血脂、睾酮、瘦素、脂联素的改善与二甲双胍相似,对体质量下降的影响不如二甲双胍.     

罗格列酮与二甲双胍治疗胰岛素控制不良2型糖尿病疗效比较

近年来,我们对胰岛素控制不良的2型糖尿病（T2DM）患者分别采用罗格列酮与二甲双胍治疗,并比较二者的疗效。现报告如下。     

二甲双胍联用磺脲类药物或罗格列酮对2型糖尿病的疗效比较

目的观察二甲双胍联用磺脲类药物或马来酸罗格列酮（RGZ）对2型糖尿病（T2DM）的疗效、优点及对肝肾功能的影响。方法将57例T2DM患者随机分为二甲双胍联用格列喹酮组（甲组）,二甲双胍联用RGZ组（乙组）,治疗12个月,观察患者治疗前后PG、BMI、HbA1c、Ins、Bp、血脂等变化,并计算胰岛素抵抗指数（HOMA-IR）。结果两组治疗均可使患者的PG、BMI、HbA1c、Bp及LDL-C下降（P〈0.05）,但乙组同时可使Ins水平下降（P〈0.01）,HOMA-IR降低（P〈0.01）。结论两组治疗方案均能明显改善T2DM患者的糖脂代谢紊乱,并可降压、减重,且对肝肾功能无影响,但二甲双胍联用RGZ可同时改善IR。     

罗格列酮和二甲双胍治疗新发2型糖尿病的疗效比较

为观察胰岛素增敏剂治疗初发2型糖尿病（T2DM）的临床疗效，新诊断T2DM患者120例被随机分为三组，分别给予马来酸罗格列酮、二甲双胍和二者联合治疗。结果马来酸罗格列酮和联合治疗明显降低新发T2DM的FPG、HbA1c、HOMA-IR，明显升高脂联素，使体重较治疗前增加。     

二甲双胍联合罗格列酮应用对2型糖尿病患者血糖的影响

目的观察二甲双胍联合罗格列酮治疗2型糖尿病时对血糖的影响。方法选取2012年3月—2014年5月经该院确诊的2型糖尿病患者100例随机分为两组,实验组给予二甲双胍联合罗格列酮,对照组给予二甲双胍,通过对患者的空腹血糖（FBG）、餐后2 h血糖（PBG）,糖化血红蛋白（GHb A1c）的测定比较两组药物的疗效情况。结果经归纳统计,两组药物在血糖控制方面均显效,实验组的疗效更显著,差异有统计学意义（P〈0.05）。结论二甲双胍联合罗格列酮较单用二甲双胍疗效显著,降糖控糖作用持久,在2型糖尿病的临床干预过程中应大力推广。     

观察二甲双胍联合罗格列酮应用对2型糖尿病者血糖影响

目的探讨观察二甲双胍及罗格列酮联合应用对于2型糖尿病者血糖水平变化影响。方法抽取该院收治于2012年11月—2014年3月的150例患者随机分为两组,观察组75人给予二甲双胍联合罗格列酮进行治疗,对照组75人给予二甲双胍治疗,比较两组患者血糖变化水平。比较两组治疗前后空腹血糖(FBG)及餐后2 h血糖水平(2hPG)。结果对照组及观察组空腹血糖(FBG)及餐后2 h血糖水平(2hPG)均降低,观察组降低水平明显优于对照组,差异具有统计学意义(P<0.05)。结论二甲双胍联合罗格列酮降糖效果优于单纯使用罗格列酮降糖,值得临床推广及应用。     

罗格列酮联合二甲双胍治疗2型糖尿病预后观察

目的探讨对2型糖尿病患者应用罗格列酮联合二甲双胍治疗的临床预后及疗效。方法选取2012年2月—2013年12月该院收治的2型糖尿病患者280例,随机分成两组,观察组采用罗格列酮和二甲双胍联合治疗,对照组单用二甲双胍治疗,通过比较两组患者初入院和治疗16周后的空腹血糖(FBG)、餐后2 h血糖(PBG)和糖化血红蛋白(HbA1c)含量变化情况,治疗前后胰岛素敏感指数和抵抗情况,分析罗格列酮联合二甲双胍治疗2型糖尿病的预后。结果观察组和对照组治疗16周后,空腹血糖、餐后2 h血糖、糖化血红蛋白均较入院时明显降低,且观察组比对照组降低更明显,差异有统计学意义(P<0.05),差异有统计学意义。观察组和对照组治疗后胰岛素敏感指数和抵抗均有所好转,且观察组比对照组变化明显,差异有统计学意义(P<0.05),差异有统计学意义。结论罗格列酮联合二甲双胍治疗2型糖尿病,可有效控制患者的血糖浓度,明显提高了患者的生活质量,效果显著。     

二甲双胍和罗格列酮治疗2型糖尿病肾病的疗效比较

糖尿病肾病足糖尿病患嚣最常见的并发症,高血糖不断侵袭毛细血管,导致肾脏血管硬化、损伤,出现蛋白尿、肾功能小伞,甚至肾衰竭,危及患者的生命,故其积极止确的治疗非常重要[1].本研究旨在比较二甲双胍和罗格列酮治疗2型糖尿病肾病的临床疗效.     

二甲双胍对假性黑棘皮病胰岛素抵抗及高胰岛素血症的作用

假性黑棘皮病 (ａｃａｎｔｈｏｓｉｓｎｉｇｒｉｃａｎｓ,ＡＮ)是一种胰岛素抵抗、高胰岛素血症、高雄激素血症的皮肤特征性改变 ,在不同的胰岛素抵抗综合征中常常伴有假性ＡＮ。胰岛素抵抗和代偿性高胰岛素血症已被证明对糖尿病、肥胖、高血压、高脂血症等疾病的发生起着重要的促进作用。及早发现和识别高胰岛素血症并给予早期干预治疗是目前临床研究的重点。二甲双胍除降低血糖外 ,可改善机体对胰岛素的敏感性 ,增加细胞的胰岛素受体数目 ,从而改善高胰岛素血症。本研究旨在观察二甲双胍对假性ＡＮ中胰岛素抵抗及高胰岛素血症、高雄激素血…     

大黄素对糖尿病KKAy小鼠PI3-K信号转导通路的影响

目的 观察大黄素对2型糖尿病模型KKAy小鼠血糖、胰岛素水平及磷脂酰肌醇3-激酶(PI3-K)信号转导通路的影响.方法 随机血糖均≥13.9 mmol/L的SPF级KKAy小鼠16只,随机分为模型组和治疗组各8只,另选8只C57BL/6J小鼠为正常组.正常组和模型组灌服20 mL/(d·kg)无菌水,治疗组予50 mg/kg大黄素灌胃.8周后测定各组小鼠空腹血糖(FPG)、空腹胰岛素(HNS)并计算胰岛素敏感指数(ISI);用Western blot法测定三组小鼠骨骼肌、脂肪组织中胰岛素受体底物-1( IRS-1)、PI3-K水平及Akt丝氨酸(Ser)473磷酸化水平.结果 模型组小鼠较正常组FPG、FINS明显升高,ISI明显降低,而治疗组小鼠的FPG、FINS较模型组明显降低,ISI明显升高(P均＜0.05).模型组IRS-1、PL3 -K表达水平及胰岛素刺激后Akt Ser473磷酸化升高倍数低于正常组,治疗组IRS-1、PI3-K表达水平及Akt Ser473磷酸化升高倍数高于模型组(P均＜0.05).结论 大黄素灌胃可降低2型糖尿病模型KKAy小鼠血糖、胰岛素水平,并增强胰岛素敏感度,提高小鼠骨骼肌及脂肪组织中的IRS-1、PI3 -K水平及Akt Ser473磷酸化水平.     

氯沙坦对自发性2型糖尿病KKAy小鼠肾脏损害的保护作用

目的探讨氯沙坦在治疗KKAy小鼠糖尿病早期肾损害中的应用价值。方法将20只雄性8周龄KKAy小鼠随机分为治疗组（n=10）和非治疗组（n=10）,治疗组从8周龄始予以氯沙坦10 mg/（kg.d）饮水喂入,C57BL/6小鼠为正常对照组（n=10）。于20周龄测定各组小鼠血糖、尿微量白蛋白、尿肌酐,并留取肾脏标本,于光镜及电镜下观察其肾脏病理改变。结果氯沙坦治疗对KKAy小鼠体质量及血糖无影响;与非治疗组比较,氯沙坦治疗减少了KKAy小鼠的尿白蛋白/肌酐比率（P〈0.05）,改善了KKAy小鼠的病理损害。结论氯沙坦治疗能减少KKAy小鼠尿白蛋白排泄率,改善肾脏病理损害。     

The effect of metformin and rosiglitazone on postprandial lipid metabolism in obese insulin-resistant subjects

INTRODUCTION: Obese insulin-resistant individuals exhibit a dyslipidaemia due to raised levels of both hepatically and intestinally derived lipoproteins. However, little is known about the related dysregulation of intestinally derived lipoproteins. We examined whether the insulin-sensitizing agents, metformin and rosiglitazone, improve intestinal lipoprotein metabolism in obese insulin-resistant individuals. METHODS: Thirty male obese (body mass index > 26; waist circumference > 100 cm) insulin-resistant [homeostasis model assessment (HOMA) score > 2.0] subjects were randomized to either a metformin (1 g bd), rosiglitazone (4 mg bd) or control treatment group for a period of 8 weeks. Fasting and postprandial lipid metabolism was studied before and after the intervention period. RESULTS: Metformin and rosiglitazone both significantly improved insulin sensitivity, but this was not paralleled by improvement in dyslipidaemia. With rosiglitazone relative to control there was a significant (p < 0.05) increase in the area under the apolipoprotein (apo) B48 curve following the oral fat load and a decrease in the ratio of triglyceride to apo B48 levels postprandially following rosiglitazone treatment. CONCLUSION: In obese insulin-resistant subjects metformin and rosiglitazone both improve insulin sensitivity, as measured by HOMA, without improvement in lipid metabolism. Rosiglitazone may have a detrimental effect on chylomicron metabolism by an increase in postprandial apo B48 levels, and this requires further investigation.     

Addition of rosiglitazone to metformin is most effective in obese,insulin-resistant patients with type 2 diabetes

Aim:   These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2D M ) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2D M who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue.
Methods:   Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2D M patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm⁻², 25–30 kgm⁻², >30 kgm⁻² respectively).
Results:   RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: −16% and +19%; 8 mg: −37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese.
Conclusions:   In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.     

Effects of pioglitazone and rosiglitazone combined with metformin on body weight in people with diabetes

Currently, pioglitazone and rosiglitazone are the thiazolidinediones available for clinical use. In the literature, there are different studies concerning the efficacy, safety and tolerability of thiazolidinediones as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin alone. Metformin and thiazolidinediones are both antihyperglycaemic drugs, both lower blood glucose concentrations in type 2 diabetes without causing overt hypoglycaemia and both require the presence of insulin to generate their therapeutic effects, but act without stimulating insulin secretion. Some authors reported that the improved glycaemic control obtained with thiazolidinediones is associated with an increase in body weight with an estimated 2–3 kg weight gain for every 1% decrease in HbA_1c which could negate some of the benefits of the improved metabolic control. Some other authors, instead, reported that thiazolidinediones give a better improvement in the glycaemic control compared with metformin alone without giving weight gain. The emerging discrepancies from these studies could be because of the study design, the patient selection, the degree of glycaemic control and/or the methods to measure body weight. We have undertaken a thorough literature search on Medline and Embase to evaluate the effects of thiazolidinediones plus metformin combination in people with diabetes on the body weight.     

Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors

Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.     

Effects of insulin-sensitising agents in mice with hepatic insulin resistance

Aims/hypothesis The metabolic abnormalities of insulin resistance are ameliorated by insulin sensitisers via different mechanisms. Metformin decreases hepatic glucose output, whereas rosiglitazone (RSG) is an agonist for peroxisome proliferator activated receptor (PPAR), highly expressed in fat. To gain insight into the mechanisms of action of these drugs, we compared their actions in two models of insulin resistance: the obese, hyperglycaemic ob/ob mouse and the liver specific insulin receptor knockout (LIRKO) mouse.Methods Control, ob/ob, and LIRKO mice were divided into three groups that received metformin (300 mg/kg body weight/day), RSG (3 mg/kg body weight/day), or placebo for 3 weeks.Results In the presence of the severe hepatic insulin resistance of the LIRKO mouse, neither metformin nor RSG had any significant effect on glucose or insulin tolerance tests. On the other hand, RSG decreased serum concentrations of total cholesterol, LDL, and HDL in LIRKO mice. Adipocyte PPAR gene and protein expression, and adipocyte size were all increased in LIRKO mice treated with RSG, whereas fat-cell size in control animals was decreased by RSG.Conclusion/interpretation TZDs probably improve some lipid parameters of the dysmetabolic syndrome associated with diabetes mellitus even in the presence of absolute hepatic insulin resistance, but both metformin and TZDs require an operating insulin signalling system in the liver for their effects in glucose homeostasis.Abbreviations TZD Thiazolidinedione - RSG rosiglitazone - LIRKO liver specific insulin receptor knockout     

Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin

BACKGROUND: Several studies have shown an increase of mortality in diabetic patients treated with combinations of sulphonylureas and biguanides. Comparisons between different insulin secretagogues in combination with metformin with respect to all-cause mortality have not been reported so far. METHODS: An observational cohort study was performed on a consecutive series of 2002 outpatients with type 2 diabetes mellitus. Of these patients, 696 (34.8%) were receiving combinations of insulin secretagogues and biguanides at enrollment. Three-year mortality was assessed through research in the City of Florence Registry Office. RESULTS: During follow-up, 295 deaths were recorded. Among patients on combined secretagogue and biguanide treatment, glibenclamide was associated with a significantly higher yearly mortality (8.7%) than repaglinide (3.1%; p = 0.002), gliclazide (2.1%; p = 0.001), and glimepiride (0.4%; p < 0.0001). After adjusting for potential confounders (including age; duration of diabetes; Body Mass Index (BMI); lipid profile; HbA(1c); insulin treatment; metformin doses; Charlson co-morbidity score; CCS), mortality remained significantly higher in patients treated with combinations of glibenclamide and metformin when compared to those treated with different insulin secretagogues (OR with 95% CI: 2.09 [1.07;4.11]). CONCLUSIONS: In the present study, sulphonylureas with greater selectivity for beta-cell receptors, such as glimepiride and gliclazide, were associated with a lower mortality when used in combination with metformin in comparison with glibenclamide. Safety of such combinations deserves further investigation.