强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效观察

目的观察强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效。方法 60例使用口服降糖药物治疗的血糖控制不佳的2型糖尿病患者,入院后先进行胰岛素泵强化控糖治疗,患者血糖达到目标值后(FPG<7.0 mmol/L,2 h PG<10.0 mmol/L),改为三餐前门冬胰岛素联合睡前甘精胰岛素继续强化治疗,1周后按1:1的比例随机分为两组,一组继续使用三餐前门冬胰岛素联合睡前甘精胰岛素治疗(对照组),一组在三餐前门冬胰岛素联合睡前甘精胰岛素的基础上加用盐酸吡格列酮30 mg/日(治疗组)。1～4周我院住院治疗,5～12周门诊随访,若出现FPG及2 h PG明显下降或低血糖反应,则减少胰岛素用量。观察加用盐酸吡格列酮治疗前以及治疗12周时FPG、2 h PG、HbAlc、胰岛素用量、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、体重指数的变化情况。结果 (1)治疗组胰岛素用量明显下降,与加用盐酸吡格列酮治疗前有明显差异(P<0.05);对照组的胰岛素用量治疗前后无明显差异(P>0.05);(2)治疗组与对照组加用盐酸吡格列酮治疗前后FPG、2hPG均无明显差异(P>0.05)。(3)治疗组HbAlc有所下降,与加用盐酸吡格列酮治疗前有明显差异(P<0.05),对照组HbAlc也有所下降,差异明显(P<0.05),但治疗后两组比较无明显差异(P>0.05)。(4)加用盐酸吡格列酮后,治疗组TG下降,HDL-C升高,与同组治疗前相比,差异明显(P<0.05),对照组与治疗前相比差异不明显,组间比较差异有显著性(P<0.05)。结论在强化控糖血糖达标后,加用盐酸吡格列酮继续治疗,可以明显降低患者胰岛素的使用剂量,提高患者的依从性,并且能改善血脂代谢紊乱,对于减少心血管并发症的发生有一定益处。     

66th Annual Meeting of the American Diabetes Association

The 66th annual meeting of the American Diabetes Association was held in Washington, DC and attracted the largest attendance ever for this meeting. This meeting continues to be grow in size and quality as the most useful and successful confluence of scientific, medical, and commercial advances relating to diabetes.     

Thiazolidinediones in the treatment of Type 2 diabetes

In the last few years there has been an explosion of research that has improved our understanding of the pathogenesis of Type 2 diabetes mellitus (DM-2) and has led to the development of new oral antidiabetic drugs. Thiazolidinediones (TZDs) are the newest of these antidiabetic agents. TZDs are insulin sensitisers that depend on the presence of insulin for their action. They target insulin resistance, which is thought to play a central role in DM-2 and the associated metabolic syndrome characterised by central obesity, hypertension, dyslipidemia and hypercoagulability, all leading to increased cardiovascular morbidity and mortality. As a result, TZDs have the potential to improve other conditions associated with the metabolic syndrome, in addition to their glycaemic action. TZDs act by activating peroxisome proliferator-activated receptor (PPAR) γ, a nuclear receptor implicated not only in lipid and glucose metabolism but other physiological functions as well. TZDs may have wide clinical applications beyond DM-2, as they can potentially be used to treat other conditions associated with insulin resistance and PPAR-γ receptors, such as impaired glucose tolerance, polycystic ovarian syndrome and HIV lipodystrophy.     

吡格列酮对2型糖尿病患者血管内皮细胞功能及胰岛素抵抗的影响

目的观察吡格列酮(PIO)治疗糖尿病患者血管内皮细胞功能的变化及其对胰岛素抵抗(IR)的影响。方法随机选取2型糖尿病伴糖耐量减低(IGT)患者60例为观察组,正常对照组30例。观察组患者用PI0 30 mg/d治疗4个月。治疗前后分别检测反应性充血肱动脉内径增加程度(FMD),含服硝酸甘油后的血管舒张幅度(NID)指标,计算胰岛素敏感指数(ISI)、组织葡萄糖摄取率(GDR)和胰岛素抵抗指数(HOMA-IR)。结果 2型糖尿病糖耐量减低患者治疗前后比较,血糖指标(FBG、HbAlc、HOMA-IR)水平降低,ISI值升高;吡格列酮治疗组与常规治疗组比较,血清脂联素无差异(P>0.05);与正常对照组比较,FMD显著降低,NID无显著性变化;治疗组FMD较治疗前升高,而NID值治疗前后无显著性变化。结论吡格列酮能增加2型糖尿病并发心血管病患者血清脂联素水平,改善IR。     

吡格列酮对老年冠心病合并糖尿病患者内皮祖细胞数量及脂联素水平的影响

目的：观察吡格列酮对老年冠心病合并糖尿病患者外周血中内皮祖细胞（EPCs）数量及血脂联素水平的影响。方法：本研究共入选65例老年（年龄≥60岁）冠心病合并糖尿病患者,随机分为吡格列酮组和安慰剂对照组,用药12周后利用流式细胞术双色分析法检测2组患者外周血中EPCs的百分比,其中EPCs以CD34＋/KDR＋双标记阳性确定,对比2组患者在服药前后EPCs数量及血脂联素水平的变化。结果：2组患者用药前EPCs数量基本相近,观察12周后吡格列酮组患者EPCs数量显著增加（0.027±0.017vs0.046±0.03,P〈0.05）,对照组患者12周后EPCs数量虽较前有所增加,但无统计学差异。12周后2组患者脂联素水平均有所增加,但吡格列酮组患者治疗前后血脂联素水平显著升高（4.5±1.7mg/Lvs7.0±2.3mg/L,P〈0.05）。结论：吡格列酮能够促进老年冠心病合并糖尿病患者EPCs的动员过程,还可提升患者血脂联素水平,可能具有抗动脉硬化功效。     

吡格列酮治疗2型糖尿病合并脑梗死患者临床疗效观察及对患者颈动脉超声的影响

目的：探讨吡格列酮治疗2型糖尿病合并脑梗死患者临床疗效观察及对患者颈动脉超声的影响。方法：选自我院于2015年1月~2016年3月期间收治的2型糖尿病合并脑梗死患者86例,依据随机数字表法随机分为观察组43例与对照组43例。对照组给予瑞舒伐他汀,观察组在对照组基础上结合吡格列酮。两组疗程均为4周。比较两组治疗疗效,治疗前后NIHSS评分、ADL评分、FPG、HbA1c、MT、颈动脉内膜斑块面积变化,及不良反应发生情况。结果：观察组治疗总有效率(90.70%)高于对照组(69.77%)(P<0.05);两组NIHSS评分治疗后下降,而ADL评分增加(P<0.05);观察组NIHSS评分治疗后低于对照组,而ADL评分高于对照组(P<0.05);两组FPG和HbA1c治疗后下降(P<0.05);观察组FPG和HbA1c治疗后低于对照组(P<0.05);两组MT和颈动脉内膜斑块面积治疗后下降(P<0.05);观察组MT和颈动脉内膜斑块面积治疗后低于对照组(P<0.05);两组心电图、血常规、尿常规、肝肾功能均未见异常,且无明显不良反应。结论：吡格列酮治疗2型糖尿病合并脑梗死患者临床疗效显著,减少颈动脉内中膜厚度和颈动脉内膜斑块面积,值得研究。     

Acid-base and electrolyte disorders associated with the use of antidiabetic drugs

Introduction: The use of antidiabetic drugs is expected to substantially increase since diabetes mellitus incidence rises. Currently used antidiabetic drugs have a positive safety profile, but they are associated with certain acid-base and electrolyte abnormalities. The aim of the review is to present the current data regarding the antidiabetic drugs-associated acid-base and electrolyte abnormalities.

Areas covered: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been linked with the scarce, but serious, complication of euglycemic diabetic ketoacidosis, as well as with an increase in serum potassium, magnesium and phosphorus levels. Metformin use has been associated with the development of lactic acidosis, although many studies have doubt the direct link with this serious complication. Additionally, metformin in some studies has been linked with a decrease in serum magnesium levels. Insulin administration is associated with a reduction in serum potassium, magnesium and phosphorus concentration, along with reduced renal magnesium excretion. Pioglitazone is associated with an increase in serum magnesium levels. Current data regarding the pathophysiological mechanisms, precipitants, risk factors and presentation of the above abnormalities are discussed in the present review.

Expert opinion: Clinicians should choose appropriately between antidiabetic drugs based not only on their hypoglycemic efficacy and effects on cardiovascular risk but also based on the patient’s specific risk to develop acid-base or electrolyte derangements.     

吡格列酮对放射性肺炎的预防作用及其机制研究

目的 过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)是一类由配体激活的核转录因子,参与调节多种炎症介质的释放,但PPARγ是否参与调节放射性肺炎尚不清楚.本实验研究PPARγ激动剂吡格列酮(pioglitazone,PIO)对放射性肺炎的预防作用,并探讨其机制.方法 将BALB/c小鼠80只随机分为正常对照组、单纯照射组、PIO治疗组及照射+PIO治疗组4组,每组20只.X射线全胸单次照射15 Gy建立小鼠放射性肺炎模型,PPARγ激动剂PIO 20 mg/ (kg·d)于照射前1周开始灌服,1次/d,每周称体质量调整1次给药剂量,共8周.分别于照射前、照射后1、4和8用处死小鼠5只,摘取全肺,称湿重,计算肺指数;行肺脏组织学HE染色观察肺组织学变化,ELISA法检测小鼠血清中转化生长因子β1(transforming growth factor beta 1,TGF-β1)、白介素6(in-terleukin 6,IL-6)和肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-口)在各组小鼠血清中的变化.结果 各组小鼠无一例死亡.资料经Kolmogorov-Smirnov检验符合正态分布,方差齐.单纯照射组小鼠肺指数最高,F=35.82,P＜0.001;照射组小鼠肺指数显著高于对照组和PIO组,均P＜0.001;照射+PIO组小鼠肺指数显著低于单纯照射组,P＜0.001.不同时间点各组小鼠肺指数差异无统计学意义,F=1.30,P=0.282.照射后肺组织发生广泛炎症改变,小血管和毛细血管扩张、充血,肺间隔和肺泡腔充斥大量水肿液体,使肺泡间隔增厚,肺泡腔减小.肺泡腔以及增厚的肺间质中充斥大量炎性细胞成分,包括巨噬细胞、中性粒细胞、淋巴细胞和红细胞等,表现为充血、水肿和渗出.PIO组则减轻了照射诱发的肺组织充血、水肿和渗出.单纯照射组小鼠TGF-β1、IL-6及TNF-α水平均高于其他3组,差异均有统计学意义,F值分别为128.80、79.18和135.51,均P＜0.001.对照组和PIO组小鼠血清TGF-β1、IL-6及TNF-α水平差异均无统计学意义,P=1.000;照射组小鼠血清TGF-β1、IL-6及TNF-α水平均显著高于对照组和PIO组(均P＜0.001),照射+PIO组小鼠血清TGF-β1、IL-6及TNF-α水平均显著低于单纯照射组(均P＜0.001).照射后4周血清TGF-β1 (F=20.62,P＜0.001)、IL-6(F=8.15,P=0.001)及TNF-α(F=5.96,P=0.005)水平最高,均显著高于照射后1周.但血清TGF-β1与照射后8周相比差异无统计学意义,P=0.460.血清TGF-β1、IL-6及TNF-α水平处理组与照射后时间之间无交互效应.血清中TGF-β1 (r=0.486,P=0.021)、IL-6(r=0.525,P＜0.001)和TNF-α(r=0.573,P=0.005)水平与肺指数呈显著正相关.结论 PPARγ激动弃 PIO能减轻小鼠放射性肺炎,其作用与可能与调节TGF-β1、IL-6和TNF-α的表达水平有关.     

Pioglitazone opposes neurogenic vascular dysfunction associated with chronic hyperinsulinaemia

BACKGROUND AND PURPOSE: We previously demonstrated that chronic hyperinsulinaemia induced by drinking high levels of fructose augments adrenergic nerve-mediated vasoconstriction and suppresses vasodilatation mediated by calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. In this study, the effects of pioglitazone on vascular responses induced by stimulation of adrenergic nerves, CGRPergic nerves and vasoactive agents were investigated in pithed rats given 15% fructose solution to drink (FDR). EXPERIMENTAL APPROACH: To assess the effect of pioglitazone on the altered vascular responsiveness in the hyperinsulinaemic state in vivo, changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II and CGRP were evaluated in pithed control rats and FDR either untreated or treated with pioglitazone.Key results: In the pithed FDR, vasoconstrictor responses to SCS and to injections of noradrenaline and angiotensin II were significantly greater than those of pithed control rats. In pithed FDR with artificially increased blood pressure and blockade of the autonomic ganglia, the vasodilator responses to SCS and CGRP injection were significantly smaller than those of pithed control rats. Oral administration of pioglitazone to FDR for two weeks markedly decreased plasma levels of insulin, triglycerides and blood glucose. In FDR pioglitazone diminished the augmented vasoconstrictor responses to SCS, noradrenaline and angiotensin II, and ameliorated the decrease in vasodilator responses to SCS. CONCLUSIONS AND IMPLICATIONS: The present results suggest that pioglitazone improves not only insulin resistance, but also the dysfunctions in vascular control regulated by adrenergic and CGRPergic nerves in the hyperinsulinaemic state.