比较地特胰岛素联合门冬胰岛素与中性精蛋白锌胰岛素联合可溶性人胰岛素对2型糖尿病住院患者疗效和安全性的随机对照研究

目的探讨使用1次/d基础胰岛素或2次/d预混胰岛素联合或未联合口服降糖药治疗但血糖控制欠佳的T2DM住院患者采用地特胰岛素+门冬胰岛素±二甲双胍方案(胰岛素类似物组)是否优效于中性精蛋白锌胰岛素+可溶性人胰岛素±二甲双胍方案(人胰岛素组)。方法两组住院治疗2周并进行有效性及安全性比较。结果两组治疗后8个时点血糖平均值较治疗前下降,两组间下降值比较差异无统计学意义(P=0.9157)。两组不良反应事件、低血糖事件发生率均较低,无严重药物不良反应和低血糖报告,胰岛素类似物组总体低血糖事件和日间低血糖发生率较人胰岛素组低(P=0.0056、0.0263)。结论胰岛素类似物和人胰岛素的基础-餐时胰岛素强化治疗方案均可改善T2DM住院患者血糖水平,但胰岛素类似物组总体低血糖和日间低血糖风险较人胰岛素组低。     

地特胰岛素、甘精胰岛素与中性鱼精蛋白锌胰岛素联合短效胰岛素治疗2型糖尿病的疗效观察

目的探讨地特胰岛素、甘精胰岛素与中性鱼精蛋白锌胰岛素联合短效胰岛素对2型糖尿病患者的疗效。方法90例2型糖尿病患者分别应用地特胰岛素、甘精胰岛素与中性鱼精蛋白锌胰岛素联合短效胰岛素治疗,比较3组治疗前后空腹血糖、餐后2h血糖、胰岛素用量及低血糖发生率。结果3组血糖均下降,但地特胰岛素组降糖效果更明显,且低血糖发生率低。结论与甘精胰岛素、中性鱼精蛋白锌胰岛素相比,地特胰岛素治疗新诊断的2型糖尿病疗效更好,低血糖发生率较低。     

门冬胰岛素30与精蛋白生物合成人胰岛素治疗老年2型糖尿病的疗效观察

目的观察门冬胰岛素30与精蛋白生物合成人胰岛素治疗老年2型糖尿病的临床疗效。方法将我院诊治的100例老年2型糖尿病患者随机分为治疗组和对照组,各50例,治疗组给予门冬胰岛素30治疗,对照组给予精蛋白生物合成人胰岛素治疗,比较两组患者的治疗效果、不良反应及血糖控制情况。结果治疗后治疗组患者在早餐后2h、晚餐后2h、睡前22:00血糖均比对照组低,差异有统计学意义(P<0.05)。结论门冬胰岛素30降糖疗效显著,低血糖发生率低,使用安全、方便,有力地保障了患者的生活质量,值得临床推广。     

地特胰岛素联合门冬胰岛素皮下注射治疗2型糖尿病效果观察

目的探讨皮下注射地特胰岛素联合门冬胰岛素治疗2型糖尿病的临床疗效及安全性,旨在为今后临床治疗2型糖尿病提供参考和依据。方法选取2011年2月—2012年2月期间应用2种以上不同类型口服降糖药、规律治疗3个月以上血糖控制欠佳的2型糖尿病患者90例并随机分为两组,均停止服用原降糖药,给予糖尿病健康教育、饮食控制等糖尿病常规治疗,在该基础上,观察组给予地特胰岛素联合门冬胰岛素皮下注射治疗,对照组给予胰岛素泵注射门冬胰岛素治疗,治疗6周后,观察并记录两组治疗前后的空腹胰岛素、C肽、餐后2 h胰岛素等水平的变化情况。结果治疗后两组患者的空腹胰岛素和C肽水平均明显高于治疗前的空腹水平,差异有统计学意义（P〈0.01）,治疗后的两组餐后2 h C肽与治疗前比较,差异无统计学意义（P〉0.05）。结论采用皮下注射地特胰岛素联合门冬胰岛素能明显改善患者的临床症状,降低低血糖发生率,提高血糖达标率,值得临床上推广应用。     

地特胰岛素与门冬胰岛素30起始治疗老年2型糖尿病伴轻度认知障碍患者的疗效比较

目的比较地特胰岛素与门冬胰岛素30起始治疗老年2型糖尿病伴轻度认知障碍(mild cognitive impairment,MCI)患者的有效性、安全性及对认知功能的影响。方法采用随机数字表法将100例老年2型糖尿病伴MCI患者分为地特胰岛素组和门冬胰岛素30组,每组50例。地特胰岛素组继续口服降糖药治疗,予地特胰岛素睡前注射;门冬胰岛素30组停用口服降糖药,予门冬胰岛素30早餐前和晚餐前皮下注射。治疗24周,观察空腹血糖(FPG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、血压、体重、体重指数(BMI)及蒙特利尔认知评估(MoCA)量表评分的变化,并记录血糖达标、低血糖及痴呆发生情况。结果两组治疗后FPG、2hPG、HbA1c、LDL-C均显著降低(P<0.05),且地特胰岛素组2hPG、HbA1c降低程度大于门冬胰岛素30组(P<0.05)。两组治疗前后TC、TG、血压、体重、BMI比较差异均无统计学意义(P>0.05)。地特胰岛素组血糖达标率高于门冬胰岛素30组(P<0.05)。两组患者治疗后低血糖发生少而轻微,不良反应发生率比较,差异无统计学意义(P>0.05),两组治疗前后MoCA量表评分比较,差异无统计学意义(P>0.05)。结论地特胰岛素与门冬胰岛素30起始治疗老年2型糖尿病伴MCI患者均安全、有效,可作为胰岛素起始治疗的首选用药。     

阿卡波糖联合地特胰岛素治疗2型糖尿病疗效观察

目的观察阿卡波糖联合地特胰岛素治疗2型糖尿病患者的疗效。方法按数字分配法将80例2型糖尿病患者分为A组（40例）采用阿卡波糖联合地特胰岛素治疗,B组（40例）采用阿卡波糖联合中性鱼精蛋白人胰岛素（NPN）治疗,观察比较两组治疗12周后空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HhA1C）、空腹C肽、餐后2hC肽（2hC肽）、体重指数（BMI）、血糖达标时间和低血糖发生率。结果两组相比,A组餐后血糖达标更快,低血糖发生率更低,体重无明显增加（P〉0．05）。结论阿卡波糖联合地特胰岛素使2型糖尿病患者血糖快速达标,该治疗方法安全、有效。     

门冬胰岛素30与门冬胰岛素联合地特胰岛素对胰岛素泵强化治疗后初发2型糖尿病患者的临床疗效对比观察

目的探讨初发2型糖尿病患者经胰岛素泵强化治疗1周后使用门冬胰岛素30与使用门冬胰岛素联合地特胰岛素治疗的临床疗效比较。方法选取于胰岛素泵强化治疗1周后的初发2型糖尿病患者60例,将患者随机分为观察组与对照组,在加强饮食、运动控制的基础上,观察组使用门冬胰岛素30三餐前皮下注射控制血糖;对照组采用门冬胰岛素联合地特胰岛素每晚睡前皮下注射控制血糖,观察两组患者的HBAIC、FPG、PPG水平及胰岛素总量。结果观察组各项观察指标与对照组比较差异没有统计学意义（P〉0．05）,且观察组注射次数减少,操作方便,受到广大医务人员及患者的认可。结论胰岛素泵强化治疗初发2型糖尿病患者后使用门冬胰岛素30与使用门冬胰岛素联合地特胰岛素治疗的临床效果无明显差异,均可保持胰岛素泵强化治疗后的血糖水平,但使用门冬胰岛素30注射较使用门冬胰岛素联合地特胰岛素治疗更容易为医务人员及患者所接受。     

门冬胰岛素联合地特胰岛素在治疗新诊断2型糖尿病中的临床效果观察

目的探究门冬胰岛素联合地特胰岛素在治疗新诊断2型糖尿病中的临床效果。方法选取该院2018年3月—2019年3月收治的2型糖尿病患者共60例,每组30例,对照组予以地特胰岛素治疗,观察组予以门冬胰岛素联合地特胰岛素治疗,对比两组患者血糖和治疗总有效率、血糖达标所用时间、发生低血糖的情况。结果在治疗前,对照组的血糖和观察组相比,差异无统计学意义(P>0.05)。经过治疗以后,对照组的血糖明显高于观察组,两组差异有统计学意义(P<0.05)。和观察组治疗效果对比,对照组治疗效果更差,差异有统计学意义(P<0.05)。观察组血糖达标花费时间明显更短,差异有统计学意义(P<0.05)。对照组患者发生低血糖概率更高,两组差异无统计学意义(P>0.05)。结论2型糖尿病治疗中应用门冬胰岛素联合地特胰岛疗效明显,有效控制血糖,延缓并发症的发生,具有值得在临床上推广和运用的优越价值。     

精蛋白锌胰岛素30R与精蛋白生物合成人胰岛素30R对口服降糖药控制不佳2型糖尿病的有效性及安全性

目的比较精蛋白锌胰岛素30R（万苏林30R）和精蛋白生物合成人胰岛素30R（诺和灵30R）对口服降糖药血糖控制不佳的2型糖尿病的有效性和安全性。方法于2009年6月至2010年6月期间将140例口服降糖药血糖控制不佳的2型糖尿病患者以1：1的比例随机分配到治疗组A和治疗组B。两组受试者分别接受精蛋白锌胰岛素30R和精蛋白生物合成人胰岛素30R治疗,根据受试者血糖初步拟定治疗剂量并随时调整,每日早、晚餐前皮下注射胰岛素并继续使用既往口服药物,治疗为期12周,12周后2组交换胰岛素继续治疗12周。观察比较2组交换胰岛素前后糖化血红蛋白（HbAlc）、空腹血糖（FBG）、餐后2h血糖（PBG）、胰岛素抗体（IAA）水平。采用配对t检验或Wilcoxon检验比较两组数据。结果治疗12周后治疗组A和B的HbAlc[（7．7±1．3）％VS（7．5±0．9）％,t=1．24,P〉0．05]、FBG[（8．0±2．0）VS（7．4±1．6）mmol／L,t=1．05,P〉0．05]、PBG[（13±4）vs（12±4）mmol／L,t=0．90,P〉0．05及IAA[（19±12）VS（19±13）mU／L,t=0．11,P〉0．05I差异无统计学意义;治疗24周后两组HbAlc[（8．3±1．5）％VS（7．5±1．0）％,x。=0．01,P〉0．05]、FBG[（7．8±2．0）VS（7．9±2．1）mmol／L,x^2=0．04,P〉0．05]、PBG[（12±4）VS（12±4）mmol／L,x^2=0．82,P〉0．05]、IAA[（19±11）VS（18±12）mU／L,X^2=1．26,P〉0．05]间差异无统计学意义。治疗组A在交叉前后低血糖发生率分别为16．4％和6．4％,治疗组B则分别为15．O％和2．9％。2组受试者未发现有局部过敏、脂肪萎缩和硬结等不良事件。结论用万苏林30R治疗口服降糖药血糖控制不佳的2型糖尿病与诺和灵30R具有相同的疗效且不会引起更多的不良反应。     

地特胰岛素替代低精蛋白胰岛素治疗2型糖尿病的疗效评估

目的研究地特胰岛素替代低精蛋白胰岛素（NPH）治疗T2DM的效果。方法用地特胰岛素替代NPH治疗30例T2DM患者,检测HbA1c、FBG及患者个体FBG变异性,体重变化以及低血糖发生率。检测时间包括在替代前12周,替代后3个阶段（每阶段均为12周）。结果HbA1c在第2、3阶段明显改善。体重从62．7kg降至61．3kg（第1阶段）,FBG明显改善,患者个体FBG变异性比使用NPH时低。结论使用地特胰岛素能良好地控制血糖,短时间体重并未增加。     

Transplantation of islets of Langerhans

The present study attempts to evaluate the possibility of using cryopreserved pancreatic islets in rats. Insulin-releasing activity was studied for the purpose of clarifying the function of cryopreserved islets. Cryopreserved pancreatic islets were also transplanted into the portal veins of recipient rats. Rats recovered from the diabetic state, and the normalized condition was maintained for up to 20 weeks, although 4 weeks were needed before blood and urine glucose reached normal levels after transplantation. Intact B cells were found in the transplanted islet cell masses in the liver of the recipients, but B cells of the recipient's pancreases (streptozotocin-treated rats) showed a marked decrease, as well as degenerative changes.     

A proteome analysis of pig pancreatic islets and exocrine tissue by liquid chromatography with tandem mass spectrometry

Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a proteome analysis method, and the shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolving power. In this study, we analyzed the protein expression in pancreatic tissue by LC-MS/MS. Islets isolated from porcine pancreata (purity ≥95%) and exocrine tissue (purity ≥99%) were used in this study. LC-MS/MS showed that 13 proteins were expressed in pancreatic islets only (Group I), 43 proteins were expressed in both islets and exocrine tissue (Group I&E), and 102 proteins were expressed in exocrine tissue only (Group E). Proteins involved in islet differentiation and cell proliferation were identified in Group I (e.g. CLUS, CMGA, MIF). In addition, various functional proteins (e.g. SCG2, TBA1A) were identified in islet by using the new method of ‘principal component analysis (PCA)’. However, the function of such proteins on islets remains unclear. EPCAM was identified in Group E. Group E was found to include proteins involved in clinical inflammatory diseases such as pancreatitis (e.g. CBPA1, CGL, CYTB, ISK1 and PA21B). Many of these identified proteins were reported less frequently in previous studies, and HS71B, NEC2, PRAF3 and SCG1 were newly detected in Group I while CPNS1, DPEP1, GANAB, GDIB, GGT1, HSPB1, ICTL, VILI, MUTA, NDKB, PTGR1, UCHL3, VAPB and VINC were newly detected in Group E. These results show that comprehensive expression analysis of proteins by LC-MS/MS is useful as a method to investigate new factors constructing cellular component, biological process, and molecular function.     

Immunological milieu in the peritoneal cavity at laparotomy for gastric cancer

AIM: To investigate the immunological repertoire in the peritoneal cavity of gastric cancer patients.METHODS: The peritoneal cavity is a compartment in which immunological host-tumor interactions can occur. However, the role of lymphocytes in the peritoneal cavity of gastric cancer patients is unclear. We observed 64 patients who underwent gastrectomy for gastric cancer and 11 patients who underwent laparoscopic cholecystectomy for gallstones and acted as controls. Lymphocytes isolated from both peripheral blood and peritoneal lavage were analyzed for surface markers of lymphocytes and their cytokine production by flow cytometry. CD4⁺CD25^high T cells isolated from the patient’s peripheral blood were co-cultivated for 4 d with the intra-peritoneal lymphocytes, and a cytokine assay was performed.RESULTS: At gastrectomy, CCR7^- CD45RA^- CD8⁺ effector memory T cells were observed in the peritoneal cavity. The frequency of CD4⁺ CD25 ^high T cells in both the peripheral blood and peritoneal cavity was elevated in patients at advanced stage [control vs stage IV in the peripheral blood: 6.89 (3.39-10.4) vs 15.34 (11.37-19.31), P < 0.05, control vs stage IV in the peritoneal cavity: 8.65 (5.28-12.0) vs 19.56 (14.81-24.32), P < 0.05]. On the other hand, the suppression was restored with CD4⁺ CD25^high T cells from their own peripheral blood. This study is the first to analyze lymphocyte and cytokine production in the peritoneal cavity in patients with gastric cancer. Immune regulation at advanced stage is reversible at the point of gastrectomy.CONCLUSION: The immunological milieu in the peritoneal cavity of patients with advanced gastric cancer elicited a Th2 response even at gastrectomy, but this response was reversible.     

猪胰岛细胞异种移植治疗糖尿病的研究进展

猪胰岛细胞移植是一种极具潜力治疗糖尿病的方法.目前仍以实验室研究为主,其临床应用主要面临两大挑战:高质量的活性胰岛短缺与异种免疫排斥反应.近年来随着胰岛分离纯化技术的改进、新型免疫耐受诱导策略的出现及移植技术的发展等,猪胰岛细胞异种移植取得了巨大的进展并进入临床前期研究.本文就猪胰岛移植物的制备、排斥反应与防治措施、移植安全性及临床研究等方面的进展作一综述.     

Failure of successful intrasplenic transplantation of islets from lean mice to cure obese-hyperglycaemic mice,despite islet growth

Summary Implantation of allogeneic pancreatic islets encapsulated in Millipore diffusion chambers has been reported to normalize the obese-hyperglycaemic syndrome in mice. In the present study, both young and adult ob/ob mice remained hyperglycaemic and gained weight after intrasplenic implantation of 500 isogeneic islets isolated from lean mice. Such islets normalized the elevated blood-glucose of alloxan-diabetic lean mice. Morphometric analysis of the intrasplenically implanted islets showed that the mean islet volume in the ob/ob mice was five times larger than that of the lean, non-diabetic mice. Immunocytochemical staining of the spleens showed an increased proportion of B-cells in the enlarged, intrasplenic islets in the ob/ob mice. Moreover, autoradiographical examination of these islets demonstrated the presence of several labelled cells. These results suggest that the growth of the implanted lean islets is due to extrapancreatic factors which stimulate islet cell replication in the obese-hyperglycaemic mouse.     

Effect of resveratrol treatment on graft revascularization after islet transplantation in streptozotocin-induced diabetic mice

We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O₂ 1%, 1hr). Some of the ITx was performed in mouse insulin 1 gene promoter-green fluorescent protein (MIP-GFP) transgenic mice and analyzed using an in vivo imaging system. After 14 days of ITx, 2-hr glucose levels on GTT in the RSV-treated group were significantly lower than those of other control groups. But the glucose status was not improved in No-ITx mice with RSV. At day 3, the percentage of Ki-67/insulin co-stained cells in islet graft was significantly increased in the RSV-ITx group. Immunostaining with anti-insulin and anti-BS-1 antibodies revealed significantly higher insulin-stained area and vascular density in RSV-treated islet grafts. The mean vessel volume per islet graft measured by in vivo imaging was significantly higher in the RSV-treated group at day 3. In isolated islets cultured in hypoxic conditions, the cell death rate and oxidative stress were significantly attenuated with RSV pretreatment. Hypoxic treatment for isolated islets decreased the expression of SIRT-1 mRNA, and this attenuation was recovered by RSV pretreatment. Our data suggest that RSV treatment improved glycemic control, beta-cell proliferation, reduced oxidative stress, and enhanced islet revascularization and the outcome of ITx in diabetic mice.     

Effects of ganglioside (Cronassial) treatment on MHC Ia antigen expression and allograft survival of pancreatic islets in diabetic rats

Summary Streptozotocin-diabetic BdII rats were treated daily with 20 mg/kg body weight gangliosides for ten days beginning two days before transplantation. This treatment did not prolong allograft survival of untreated Lewis islets. Culture treatment of isolated Lewis islets with gangliosides (100 g/ml in RPMI 1640) for one day resulted in a significant reduction of MHC Ia antigen positive cells but not of class I antigens within the islets. Tranplantation of the ganglioside pretreated islets into non-immunosuppressed BdII recipients prolonged allograft survival to 12 days only in one of five animals.