丹芪参杞降糖汤和盐酸吡格列酮联合治疗糖尿病疗效观察

目的:探讨丹芪参杞降糖汤和盐酸吡格列酮联合治疗糖尿病的临床疗效。方法:选择我院2009年6月～2011年10月采用丹芪参杞降糖汤联合盐酸吡格列酮治疗的72例糖尿病患者作为观察组,另选择同期单纯应用盐酸吡格列酮治疗的72例患者为对照组,对两组患者的临床资料进行回顾性分析,比较两组患者临床治疗总有效率及不良反应发生率。结果:治疗3个月后,观察组总有效率为94.44%,明显高于对照组的81.94%;差异有统计学意义(P0.05)。两组不良反应率比较,差异无统计学意义(P0.05)。结论:联合应用丹芪参杞降糖汤和盐酸吡格列酮治疗糖尿病疗效明显,优于单纯西药治疗。     

Insulin Resistance Reduces Sensitivity to Cis-Platinum and Promotes Adhesion,Migration and Invasion in HepG2 Cells

The liver is normally the major site of glucose metabolism in intact organisms and the most important targetorgan for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated withpostoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drugresistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubationwith a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biologicaleffects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells weredetermined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition,the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IRcells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited alower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatmentwith the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drugresistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain theclinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasionand migration of cancer cells.     

2种口服降糖药物联合胰岛素治疗初诊2型糖尿病的临床对比研究

目的：探讨2种口服降糖药物分别联合人工合成胰岛素对初诊2型糖尿病（T2DM）的患者血糖指标、胰岛β细胞功能及低血糖发生率的影响。方法：研究对象选取某院2013年4月-2015年12月收治初诊T2DM患者共120例,以随机数字表法分为A组（60例）和B组（60例）,分别在甘精胰岛素应用基础上加用罗格列酮和格列美脲辅助治疗;比较2组患者血糖达标时间,胰岛素用量,治疗前后BMI水平、血糖指标水平、胰岛β细胞功能指标水平、低血糖及心血管疾病发生率等。结果：2组患者血糖达标时间和胰岛素用量比较差异无显著性意义（P>0.05）;B组患者治疗后BMI水平显著低于A组（P<0.05）;2组患者治疗后血糖和胰岛β细胞指标水平组间比较差异无显著性意义（P>0.05）;同时B组患者低血糖发生率显著低于A组（P<0.05）;2组患者心血管疾病发生率比较差异无显著性意义（P>0.05）。结论：罗格列酮和格列美脲分别联合人工合成胰岛素治疗初诊T2DM临床疗效接近,但格列美脲口服可有效减少体质量增加量,降低低血糖发生风险,更具临床应用价值。     

Preventing progression from gestational diabetes mellitus to diabetes: A thought‐filled review

Women with a history of gestational diabetes are at high risk for developing type 2 diabetes mellitus. In studies with long periods of follow‐up, diabetes incidence of up to 70% has been reported. The appropriate follow‐up of women following a pregnancy complicated by gestational diabetes has not been studied. Published guidelines recommend that obstetrician/gynaecologists, who are often the de facto primary care physicians for these otherwise healthy young women, incorporate glucose monitoring in the post‐partum period into their annual examinations. In reality, reported rates of screening have been low. There is also no clear evidence for any beneficial interventions to prevent diabetes in patients with prior history of gestational diabetes. Lifestyle intervention programmes for diabetes prevention among these patients yielded disappointing results. Metformin, pioglitazone, liraglutide, and bariatric surgery are possible options but based on inadequate data. There remains a need for randomized, placebo‐controlled studies to evaluate various pharmacologic treatments, with and without lifestyle interventions, to prevent type 2 diabetes mellitus in women with a history of gestational diabetes.     

Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

Background  Pioglitazone is effective in nonalcoholic steatohepatitis (NASH), but the mechanisms of action are not completely understood. This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenases-2 (COX-2) expression in NASH rats.

Methods  Thirty Sprague-Dawley male rats were randomly assigned to a control group (n=10), NASH group (n=10), and pioglitazone treatment group (n=10). Liver tissues were processed for histology by hematoxylin & eosin and Masson stained. Serum alanine aminotransferase (ALT), cholesterol, triglyceride, fasting blood glucose (FBG), fasting insulin (FINS) levels and biochemical parameters of antioxidant enzyme activities, tumor necrosis factor alpha (TNF-α), prostaglandin E₂ (PGE₂) levels in serum and liver were measured. The mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARγ), NF-κB and COX-2 were determined by real-time polymerase chain reaction, Western blotting and immunohistochemistry. One-way analysis of variance (ANOVA) and Wilcoxon’s signed-rank test was used for the statistical analysis.

Results  There were severe steatosis, moderate inflammatory cellular infiltration and fibrosis in NASH rats. After pioglitazone treatment, steatosis, inflammation and fibrosis were significantly improved compared with the NASH group (χ²=20.40, P <0.001; χ²=20.17, P <0.001; χ²=13.98, P=0.002). Serum ALT, cholesterol, triglyceride, FBG, FINS levels were significantly elevated in the NASH group (P <0.05). In the NASH group, total anti-oxidation competence (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels in serum and liver were conspicuous disordered than those parameters in the control group. Meanwhile, TNF-α and PGE₂ levels in serum and liver were significantly increased compared with the control group. Immunohistochemistry showed NF-κB and COX-2 expression in liver was significantly elevated. However, PPARγ level was decreased in the NASH group. Real-time PCR and Western blotting revealed mRNA and protein expression of COX-2 were increased in the NASH group compared with the control group (0.57±0.08 vs. 2.83±0.24; 0.38±0.03 vs. 1.00±0.03, P <0.001 and P=0.004, respectively). After pioglitazone intervention, all of those parameters markedly improved (P <0.05 or P <0.01).

Conclusion  Down-regulating hepatic NF-κB and COX-2 expression, at least in part, is one of the possible therapeutic mechanisms of pioglitazone in NASH rats.

     

HPLC法测定盐酸吡格列酮片的含量

采用反相 ＨＰＬＣ法,以Ｃ１８为固定相,乙腈－１０ｍｍｏｌ／Ｌ醋酸铵缓冲液（ｐＨ ６．０）（６０： ４０）为流动相,检测波长为２２９ｎｍ,流速为１．０ｍｌ／ｍｉｎ,测定了盐酸吡格列酮片的含量。线性范围为１０～２００μｇ／ｍｌ,平均回收率为９９．７３％（ＲＳＤ＝１．２２％）。     

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。     

Combinations of ezetimibe with nonstatin drug regimens affecting lipid metabolism

In this article we discuss the available data on the effects of combined therapy of ezetimibe with agents affecting lipid metabolism other than statins. We consider studies evaluating the effects of combined therapy of ezetimibe with bile acid sequestrants, fenofibrate, niacin, n-3 fatty acids, plant sterols, orlistat, metformin, acarbose and glitazones. Combination of ezetimibe with bile acid sequestrants (especially colesevelam) was shown to have additional effects on lipid parameters in patients with hyperlipidemia. Combination of ezetimibe with fenofibrate may be a good approach to improve the overall lipid profile of patients with mixed hyperlipidemia. The addition of ezetimibe to niacin-based therapy can be useful for high-risk patients with dyslipidemia who are not achieving their assigned treatment goals. For patients who cannot tolerate statins there are useful combinations of ezetimibe with other drugs affecting lipid metabolism. These combinations improve many metabolic parameters, but more trials should be carried out to reach more robust conclusions about their effects on cardiovascular disease prevention.     

A case of secondary diabetes mellitus with acromegaly improved by pioglitazone.

AIM: The acromegaly patient was diagnosed with Type 2 diabetes mellitus. His HbA1c was 10.6% and fasting blood glucose (FBG) 15.3 mmol/l. We prescribed glibenclamide (10 mg/day), but his HbA1c and FBG remained high. At this stage, treatment with short-acting insulin was instigated at a dose of 20 U/day. However, the patient's blood glucose level remained unsatisfactory. We tried using pioglitazone. METHOD: Pioglitazone was prescribed at 30 mg/day in combination with the insulin. RESULTS: The FBG and HbA1c value decreased to 7.2 mmol/l and 7.3%, respectively, within 2 months and insulin was discontinued. Pioglitazone alone was able to control the FBG level. CONCLUSIONS: Pioglitazone treatment might be considered as a choice for similar cases of diabetes secondary to acromegaly.