脑梗死患者体内胰岛素抵抗和红细胞胰岛素受体的关系

背景流行病学研究显示胰岛素水平升高和冠状动脉疾患相关,代谢研究也表明胰岛素抵抗、高胰岛素血症和非胰岛素依赖性糖尿病、高血压、肥胖及脂质紊乱密切相关.目的探讨脑梗死患者体内胰岛素抵抗与红细胞胰岛素受体之间的关系.设计病例-对照观察.单位吉林大学中日联谊医院神经内科.对象选择40例2004-01/10在吉林大学中日联谊医院住院的脑梗死患者.同时选取了30例健康的医护人员作为对照组.方法检测脑梗死患者和对照者的空腹血糖、血清胰岛素及葡萄糖耐量试验后2 h的血糖、血清胰岛素浓度,并将空腹血糖和血清胰岛素浓度的乘积作为胰岛素抵抗指标.采用改良甘氏法检测红细胞胰岛素受体,同时分析胰岛素受体数目与胰岛素抵抗指标的关系.主要观察指标脑梗死组与正常对照组①空腹及葡萄糖耐量试验后2 h血糖和血清胰岛素的比较.②胰岛素抵抗指标比较.③红细胞胰岛素受体分析.结果40例脑梗死患者和30例对照者的数据均进入结果分析,无脱落者.①空腹及葡萄糖耐量试验后2 h血糖和血清胰岛素的比较脑梗死组空腹血清胰岛素、葡萄糖耐量试验后2 h血糖和胰岛素均大于正常对照组[(13.30±5.15),(9.85±4.36)mU/L,(8.27±1.65),(6.32±1.37)mmol/L,(75.21±21.12),(28.26±6.31)mU/L,P＜0.01,P＜0.001].②胰岛素抵抗指标比较脑梗死组大于正常对照组(68.69±22.91,48.36±10.16,P＜0.001).③红细胞胰岛素受体分析脑梗死组每个红细胞膜胰岛素高、低两型亲和力受体数目及最大特异性结合率均小于正常对照组[20.30±4.50,23.80±4.10;2 223.80±509.30,2 610.10±435.10;(10.62±3.55)%,(13.21±2.94)%,P均＜0.01];直线回归与相关分析表明脑梗死患者胰岛素高、低两型亲和力受体数目与胰岛素抵抗指标呈负相关(r=-0.458,-0.439,P均＜0.01).结论脑梗死患者体内存在着胰岛素抵抗;胰岛素受体数目减少在胰岛素抵抗引发的脑梗死中起着重要作用.     

糖耐量异常与动脉粥样硬化发病的相关性

背景：糖耐量异常是动脉粥样硬化潜在的危险因子,但糖耐量异常与动脉粥样硬化的确切关系尚未阐明.目的：探讨糖耐量异常患者糖耐量的异常变化与动脉粥样硬化发病的关系.设计：观察对比实验.单位：解放军总医院心内科.对象：选择2001-01/2002-02在解放军总医院就诊的血糖异常升高患者221例,均自愿参加观察.男135例,女86例,年龄（52&;#177;10）岁.方法：①受试者于空腹过夜10～14 h后食用含至少150 g碳水化合物的食物3 d,口服溶于250 mL水内的无水葡萄糖粉75 g.分别取空腹及服糖后2 h静脉血标本,立即离心分离血浆.②按照预先设计的调查表格记录患者的病史,空腹过夜12 h后测量空腹胰岛素、总胆固醇、三酰甘油及高、低密度脂蛋白胆固醇水平.③使用高频B型超声检查颈动脉,用频率10 MHz的线阵探头扫描双侧颈总动脉,测量内膜内侧缘至中膜外侧缘之间的距离,即为内中膜厚度.④按照1999年世界卫生组织的诊断标准进行糖耐量分型.糖尿病为空腹血糖≥7.0 mmol/L或服糖后2 h血糖≥11.1 mmol/L;糖耐量异常为空腹血糖＜7.0 mmol/L和7.8 mmol/L≤服糖后2 h血糖＜11.1 mmol/L;正常糖耐量为空腹血糖＜6.1mmol/L和服糖后2 h血糖＜7.8 mmol/L.高血压标准为收缩压≥160 mm Hg（1 mm Hg=0.133 kP）,舒张压≥95 mm Hg.以颈动脉内中膜厚度≥1.2 mm定为斑块.颈动脉内膜光滑性分级：光滑性及连续性好,内膜无粗糙区为0;光滑性较差为1;明显差为2.主要观察指标：各组观察对象的一般情况、血脂水平及颈动脉颈动脉内中膜厚度.结果：221例血糖异常升高者全部进入结果分析,无脱落.①血糖异常升高患者分为3组,正常糖耐量组97例,糖耐量异常组51例,糖尿病组73例.②各组观察对象动脉粥样硬化一般情况的比较：糖耐量异常组三酰甘油、低密度脂蛋白胆固醇、空腹胰岛素水平及胰岛素抵抗指数显著高于正常糖耐量组[（1.79&;#177;0.89,3.31&;#177;0.52）mmol/L,（5.90&;#177;3.02）mU/L,1.52&;#177;0.86;（1.49&;#177;0.83,3.07&;#177;0.66）mmol/L,（3.91&;#177;2.08）mU/L,（0.93&;#177;0.54）（t=2.038～5.113,P＜0.05～0.01）],高密度脂蛋白胆固醇水平显著低于正常糖耐量组[（1.17&;#177;0.28,1.39&;#177;0.32）mmol/L,（t=4.145,P＜0.01）].除胰岛素抵抗指数外,以上指标糖尿病组与糖耐量异常组之间的差异无显著意义（P＞0.05）.③各组观察对象颈动脉粥样硬化的相关指标比较：糖耐量异常组的平均内中膜厚度、内膜光滑性评分均显著高于正常糖耐最组[（0.80&;#177;0.20,0.73&;#177;0.15）mm;2.10&;#177;1.37,1.55&;#177;1.23（t=2.398,2.485,P＜0.05）].④Logistic回归分析：年龄、总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平与糖耐量异常相关（P＜0.05～0.01）.结论：糖耐量异常患者存在明显的动脉粥样硬化表现,其程度与糖尿病患者接近.     

脑梗死患者血清瘦素、胰岛素敏感指数与梗死体积及神经功能缺损的关系

目的：观察瘦素、胰岛素敏感指数在脑梗死患者急性期血清水平变化，探讨其与患者梗死体积及神经功能缺损的关系。 方法：选择华北煤炭医学院附属医院2004-02／2005-02收治的86例急性脑梗死患者为观察对象。测定其急性期血清中的瘦素、胰岛素、血糖、胰岛素敏感指数的水平，与同期健康体检者31例对照。将脑梗死患者按梗死体积分为小梗死组（〈5cm^3），中梗死组（5-15cm^3），大梗死组（〉15cm^3）；根据神经功能缺损程度评分分为轻度损伤组（0～15分），中度损伤组（16～30分），重度损伤组（31-45分），比较不同梗死体积和损伤程度时瘦素水平、胰岛素抵抗程度的变化，并进行血清瘦素与胰岛素抵抗之间的直线相关和回归分析。 结果：按实际处理分析，117例观察对象全部进入结果分析。①脑梗死组的血糖、瘦素水平显著高于对照组[（7．05&;#177;2．22），（5．39&;#177;0．88）mmol／L；（17．85&;#177;15．09），（9．21&;#177;4．76）μg／L，（P〈0．05）]，胰岛素、胰岛素敏感指数显著低于对照组[（11．22&;#177;3．35），（19．75&;#177;8．06）mIU／L；-0．94&;#177;0．52，-1．89&;#177;0．79，（P〈0．05）]。②脑梗死体积越大，脑梗死患者血清中瘦素、胰岛素、血糖越高（F=15．79～12．00，P〈0．05），胰岛素敏感指数越低（F=24．27，P〈0．05）。③神经功能缺损程度越重，脑梗死患者血清中瘦素、胰岛素、血糖越高（F=14．28～11．00，P〈0．05），胰岛素敏感指数越低（F=23．24，P〈0．05）。④直线与相关回归分析表明瘦素与胰岛素、血糖呈显著正相关（r=0．53，0．26，P〈0．001），与胰岛素敏感指数呈显著负相关（r=-0．66，P〈0．001）。 结论：①脑梗死体积越大，神经功能缺损评分越高，瘦素水平越高，胰岛素抵抗程度越重，提示瘦素抵抗，胰岛素抵抗可加重缺血性脑损害。②瘦素水平越高，胰岛素抵抗程度越重，脑梗死体积越大，神经功能缺损评分越高，提示观测脑梗死患者血清瘦素水平及胰岛素抵抗程度对脑组织损伤程度及预后判断有一定的价值。③瘦素抵抗与胰岛素抵抗可能相巨促进．相互影响促进脑梗死的发生，加重病情。     

西布曲明治疗肥胖的疗效及对肥胖患者血生化学和胰岛素敏感性指标的影响

目的：观察作用于中枢神经系统的减肥药西布曲明对单纯性肥胖症者体质量、腰臀比、血生化学指标及胰岛素敏感性指标的作用效果.方法：①选择2002-12/2003-3福建医科大学附属协和医院门诊就诊的52例单纯性肥胖者,年龄18～65岁.均对实验目的知情同意,并配合实验.每日晨服用盐酸西布曲明胶囊1片,共12周.②每4周纳入对象回本院复诊1次,测定体质量、腰围、臀围,计算体质量指数[体质量（kg）/身高（m^2）]和腰臀比[腰围（cm）/臀围（cm）].治疗前及治疗12周后采用全自动生化仪测定空腹血糖、总胆固醇、三酰甘油.采用化学发光免疫分析仪测定血清胰岛素水平.计算胰岛素抵抗指数（空腹血糖&;#215;空腹胰岛素/22.5）,胰岛素敏感指数[1/（空腹血糖&;#215;空腹胰岛素）],β细胞功能[20&;#215;空腹胰岛素/（空腹血糖-3.5）].③计量资料差异比较采用方差分析和t检验.结果：单纯性肥胖者52例均进入结果分析.①盐酸西布曲明治疗12周后肥胖者体质量、体质量指数、腰围、臀围明显低于治疗前（t=3.24,3.16,4.06,1.99,P＜0.05）,治疗前后腰臀比差异不明显.②治疗12周后血总胆固醇、三酰甘油水平明显低于治疗前[（5.00&;#177;0.83）,（1.15&;#177;0.75）mmol/L;（5.39&;#177;0.99）,（1.47&;#177;0.72）mmol/L,t=2.19,2.23,P＜0.05],而空腹血糖和低密度脂蛋白胆固醇无明显变化.③治疗前后胰岛素水平、胰岛素敏感指数、胰岛素抵抗指数和β细胞功能无明显变化（P＞0.05）.结论：盐酸西布曲明胶囊有显著减重效果,并能有效改善血脂,但对胰岛素敏感性指标无明显影响.     

急性脑梗死患者肿瘤坏死因子α与胰岛素抵抗的关系

背景：肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)和胰岛素抵抗(insulin resistance，IR)都是脑血管病的危险因素，拮抗TNF-α能否改善IR及减轻脑血管病患者脑损伤?目的：探讨急性脑梗死患者TNF-α和IR的改变及其相互关系。设计：以诊断为依据的病例对照研究。地点和对象：广西壮族自治区百色市人民医院2000-01／2003-02符合全国第二次脑血管病会议诊断标准的48例急性脑梗死患者(急性脑梗死组)和36例健康体检者(正常对照组)。干预：所有入选对象均于清晨空腹抽取静脉血测定血糖(fasting plasma glucose，FPG)，血清胰岛素(fasting insulin，FINS)，TNF-α。血糖测定方法采用氧化酶法，血清胰岛素测定用放射免疫法，TNF-α采用酶标法。主要观察指标：急性脑梗死组和正常对照组的FPG，FINS，TNF-α的水平。结果：急性脑梗死组的TNF-α水平为(205&;#177;78)ng／L，FINS为(6．18&;#177;1．72)mmol／L，FPG为(12．74&;#177;4．33)mU／L，均高于对照组[(76&;#177;18)ng／L，(5．25&;#177;1．28)mmol／L，(7．18&;#177;2．58)mU／L]。其中急性脑梗死组的TNF-α水平和FINS与对照组比较，差异有显著性意义(t=9．72，7．33，P&;lt;0．01)；血清TNF-α与FINS呈正相关(r=0．53．P&;lt;0．01)。结论：急性脑梗死患者可有IR和TNF-α水平增高，TNF-α与IR有密切相关性，两者可能共同参与缺血性脑血管病的发生和发展，拮抗TNF-α有可能改善胰岛素抵抗及减轻脑缺血患者的脑损伤。     

维持性血液透析患者血清脂联素水平与胰岛素抵抗的关系初探

目的 探讨维持血液透析（MHD）患者血清脂联素（ADPN）水平与胰岛素抵抗的关系.方法 选择首都医科大学附属北京朝阳医院肾内科60例MHD患者和30例正常对照者,分别测定血清ADPN水平、空腹胰岛素（FINS）及空腹血糖（FBG）,并根据公式计算胰岛素敏感指数（ISI）和稳态模型胰岛素抵抗指数（Homa-IR）.结果 MHD组的FINS、FBG、Homa-IR明显高于对照组（P＜0.01）,ISI明显低于对照组（P＜0.01）.MHD组和对照组血清ADPN水平分别为（23.75±8.97）mg/L和（9.13±3.39）mg/L,两者间差异具有显著性（P＜0.05）.相关分析表明,血清ADPN与FINS、ISI呈明显正相关（r分别为0.453、0.534,P均＜0.01）,而与Homa-IR呈明显负相关（r为-0.471,P＜0.01）.结论 维持性血液透析患者血清ADPN水平升高,血清ADPN水平与维持性血液透析患者胰岛素抵抗密切相关.     

高血压患者的胰岛素抵抗

目的探讨高血压与胰岛素抵抗之间的关系。方法选取2001-02／2003—04山东省立医院保健神经科和解放军济南军区总医院神经科患者62例，根据有无高血压分为正常对照组30例和高血压组32例，其中高血压Ⅰ期组9例，Ⅱ期组8例，Ⅲ期组15例。两组患者均抽血测定空腹血糖、胰岛素、C肽、胆固醇和三酰甘油浓度，口服葡萄糖1，2h后，分别再次抽血检测以上指标，将正常对照组和高血压组的检测结果进行比较，并将高血压组各期之间进行相关指标的比较。结果62例患者全部纳入结果分析。两组性别、年龄、体质量指数等差异无显著性意义（P〈0．05）。高血压组的空腹血糖、胰岛素和血清总胆固醇浓度[（5．84&;#177;0．82）mmol／L，（18．94&;#177;4．24）mIU／L,（5．78&;#177;9．47）mmol／L]，均明显高于正常对照组[（5．02&;#177;0．51）mmol／L，（7．63&;#177;5．22）mIU／L，（5．02&;#177;0．64）mmol/L]（P〈0．05），血清三酰甘油浓度两组间无显著差异（P〉0．05）；饮糖水后1，2h高血压Ⅰ，Ⅱ，Ⅲ期组血糖均增高，Ⅱ期组饮糖水后1h血糖[（9．87&;#177;2．84）mmol／L]高于Ⅰ期组[（6．88&;#177;1．75）mmol／L]，比较有显著性差异（P〈0．05）；Ⅰ期组饮糖水后1，2h胰岛素显著增高[（74．67&;#177;13．44，35．72&;#177;9．45）mIU／L，（P〈0．05）]，Ⅱ，Ⅲ期组空腹和饮糖水后1，2h胰岛素也显著增高（P〈0．05），Ⅲ期组饮糖水后1，2h胰岛素[（98．66&;#177;14．84），（88．67&;#177;24．65）mIU／L]高于Ⅱ期组[（85．41&;#177;16．02），（68．30&;#177;36．63）mIU／L，（P〈0．05）]；Ⅰ，Ⅱ，Ⅲ期高血压组与正常对照组相比C肽差异均有显著性。结论高血压与胰岛素抵抗有关，胰岛素抵抗和高胰岛素血症可能是高血压的发病机制之一。治疗高血压要考虑纠正胰岛素抵抗。     

糖耐量低减患者红细胞胰岛素酶活性与胰岛素抵抗

背景：糖耐量低减发病主要与遗传和环境因素有关，环境因素包括摄入热量过多和肥胖等。胰岛素抵抗是其主要发病机制之一。目的：探讨糖耐量低减患者的红细胞胰岛素酶活性(erythrocyles insulinase actlvity，EIA)与胰岛素抵抗的关系，为运动改善糖耐量低减患者的胰岛素抵抗提供理论支持。设计：以IGT患者为研究对象，以正常糖耐量的成年人为对照组的观察对比研究。单位：一所军医大学医院的内分泌科。对象：本研究于2001—01／2003—04在第一军医大学南方医院内分泌科完成。随机抽取住院和门诊的糖耐量低减患者50例，男26例，女24例，年龄(52&;#177;7)岁。纳入标准：符合WHO1999年口服葡萄糖耐量实验(OGTT)的糖耐量低减诊断标准，心、肝、肾功能和血常规均在正常范围，且未使用任何抗糖尿病药物者。排除标准：患肝脏、肾脏疾患、感染、恶性肿瘤、冠心病、脑血管意外和结缔组织疾病者。根据是否合并空腹血糖异常将糖耐量低减患者分为合并空腹血糖异常的糖耐量低减1组，共20例，男9例，女11例；单纯餐后高血糖未合并空腹血糖异常的糖耐量低减2组，共30例，男17例，女13例。20例正常糖耐量的成年人作为对照组，男女各10例，年龄(48&;#177;12)岁。方法：用放射酶分析法检测所有研究对象的EIA，同时检测患者的血糖、血清胰岛素和糖基化血红蛋白，并计算稳态模型胰岛素抵抗指数(Homeostasis Model Analysis-insuIin resistance index，HOMA-IR)以评价机体的胰岛素敏感性。主要观察指标：各组EIA水平和HOMAIR指数的差异和相互关系。结果：糖耐量低减患者的EIA、血清空腹胰岛素和HOMA-IR指数显著高于对照组(P&;lt;0．01或P&;lt;0．05)；糖耐量低减1组患者的EIA和HOMA-IR显著高于糖耐量低减2组(P&;lt;0．01)；直线回归分析表明，糖耐量低减患者的EIA与血清空腹胰岛素、糖基化血红蛋白、HOMA-IR指数呈显著正相关(P&;lt;0．01)。结论：糖耐量低减患者的红细胞胰岛素酶降解速度显著高于正常人，并与其胰岛素抵抗的发生、发展有密切相关性。     

罗格列酮对糖尿病患者血清肿瘤坏死因子α水平及胰岛素抵抗的干预效应

目的：运用胰岛素增敏剂罗格列酮治疗2型糖尿病患者,观察其在改善血糖、血脂、胰岛素抵抗的同时对血清肿瘤坏死因子α水平的影响.方法：①选择2004-03/07深圳市罗湖区人民医院内分泌科住院的2型糖尿病患者26例为糖尿病组.纳入同期本院体检科健康体检人员26例作为对照组.均对实验目的知情同意.②糖尿病组在严格糖尿病饮食、运动和原有口服药物的基础上服用马来酸罗格列酮,4mg/次,1次/d,共干预12周.③采用自动生化分析仪测定总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹血糖、餐后血糖.采用放射免疫法测定空腹胰岛素、餐后胰岛素.采用RIA Kit测定血清肿瘤坏死因子α水平.计算胰岛素抵抗指数=（空腹胰岛素&;#215;空腹血糖）/22.5,计算胰岛素敏感性指数=1/（空腹胰岛素&;#215;空腹血糖）.④组间比较采用t检验,采用直线相关分析.结果：糖尿病患者26例和健康体检者26人均进入结果分析.①糖尿病组治疗前肿瘤坏死因子α、总胆固醇、三酰甘油、低密度脂蛋白胆固醇、空腹血糖、餐后血糖明显高于对照组（P＜0.05～0.01）,高密度脂蛋白胆固醇明显低于对照组（P＜0 05）.糖尿病组治疗后肿瘤坏死因子α、三酰甘油、空腹血糖、餐后血糖明显低于治疗前（P＜0.05～0.01）,高密度脂蛋白胆固醇明显高于治疗前（P＜0 05）.②糖尿病组治疗前空腹胰岛素、餐后胰岛素、胰岛素抵抗指数明显高于治疗后和对照组（P＜0.05～0.01）,胰岛素敏感指数明显低于治疗后和对照组（P＜0.05）.③糖尿病组治疗前肿瘤坏死因子α与胰岛素敏感指数呈显著负相关（r=-0.38,P＜0.05）,与胰岛素抵抗指数呈显著正相关（r=0.29,P＜0.05）.治疗后肿瘤坏死因子α与胰岛素敏感指数呈显著负相关（r=-0.31,P＜0.05）,与胰岛素抵抗指数呈显著正相关（r=0.26,P＜0.05）.结论：①罗格列酮可使糖尿病患者血清肿瘤坏死因子α下降,胰岛素敏感性增加,胰岛素抵抗得到改善.②罗格列酮可以升高高密度脂蛋白胆固醇,降低高血脂和高血糖水平等多种心血管风险因素,纠正一系列代谢异常,从而对心血管起到保护作用.     

糖尿病合并脑梗死患者胰岛素抵抗与内皮素的关系

目的：检测糖尿病脑梗死患者血浆内皮素水平与胰岛素敏感指数，探讨两者的关系。方法：选择肇庆市第一人民医院内分泌科、神经内科2002-09／2004-06收治的符合2型糖尿病和脑梗死诊断标准的住院、门诊患者为观察对象。全部病例均经头颅CT或MR证实，且脑梗死发生于2d内，排除冠心病病史患者；服用抗凝药物华法林的患者。符合以上标准的56例患者根据脑梗死严重程度分为2型糖尿病合并轻型脑梗死组35例和2型糖尿病合并中重型脑梗死组21例；选择28例单纯性脑梗死患者，28例单纯性2型糖尿病患者为对照组。采用放射免疫法检测各组患者及对照组空腹血浆胰岛素、内皮素，并计算胰岛素敏感指数。结果：112例患者血样合格，测量结果进入统计分析。①胰岛素敏感指数结果：2型糖尿病合并轻型脑梗死组、2型糖尿病合并中重型脑梗死组显著低于单纯性糖尿病组[（0．8&;#177;0．4）％，（0．6&;#177;0．3）％，（1．2&;#177;0．3）％，P=0．02，0．00]，而且2型糖尿病合并中重型脑梗死组明显低于2型糖尿病合并轻型脑梗死组（P=0．02）。②内皮素水平检测结果：单纯性糖尿病组与单纯性脑梗死组血浆内皮素水平差异不显著[（91．3&;#177;26．3），（89.8&;#177;19．8）ng／L]，2型糖尿病合并轻型脑梗死组，2型糖尿病合并中重型脑梗死组的内皮素显著高于单纯糖尿病组[（99．3&;#177;23．3），（127．6&;#177;33．2），（91．3&;#177;26．3）ng／L，（P=0．03）]。分层对比分析显示，56例糖尿病性脑梗死患者血浆内皮素水平与性别、年龄、高血压等无关，而与胰岛素敏感指数有关。结论：脑卒中发生后2型糖尿病患者血浆内皮素水平明显升高，同时存在明显的与疾病严重程度相关的胰岛素抵抗；血浆内皮素水平与胰岛素抵抗有关。胰岛素抵抗和升高的内皮素水平可能在糖尿病脑梗死患者脑损伤中起到重要作用。     

The human insulin analogue insulin lispro

Insulin lispro is a newly developed analogue of human insulin where the positions of the amino acids lysine and proline have been switched at the end of the B chain of the insulin molecule. Insulin lispro with lysine at position B28 and proline at position B29 has a weaker tendency for self-association than human insulin. This leads to three major differences in the pharmacokinetics: the action begins faster, has a higher peak and the duration is shorter than with human insulin. Thus, insulin lispro has a more precise action profile for the mealtime than human regular insulin. Insulin lispro is recommended to be injected within 15 min before the meal in contrast to 30–40 min for human insulin. In clinical trials with insulin lispro, the postprandial rise of blood glucose is smaller, the rate of hypoglycaemia is lower particularly at night-time, the need for snacks is smaller and the patient preference is better than with human insulin. The long-term control as reflected by an improvement in the HbA_]c level is better with insulin lispro than with human regular insulin, provided that an appropriate basal insulin regimen is used to take into account the shorter duration of action. A few patients have been described who have a severe resistance to human insulin but who have been succesfully treated with insulin lispro. Insulin lispro was designed to be used as a mealtime insulin, and it is a step forward in the treatment of diabetic patients using a basal-bolus insulin regimen.     

Inhaled insulin (pulmonary administered insulin)]

The first report according to Inhaled insulin came out in 1924. Recent clinical trials of inhaled insulin made a real story to insulin-treated diabetic patients. Among some companies, insulin preparation of Pfizer company group consists of dry insulin dispersed by aerosol into particles sufficiently fine to drift into the distal twigs of the respiratory tree. Skylar et al in 2001 reported a randomized proof-of-concept study of inhaled insulin in type 1 diabetes mellitus. The result showed the same efficacy to the same time injections of regular insulin. Other reports showed the efficacy of inhaled insulin comparable to that of lispro insulin and the same action to not only type 1 but also type 2 diabetic patients.     

Changes in insulin resistance with long-term insulin therapy

Thirteen newly diagnosed diabetic subjects, 5 with insulin-dependent diabetes mellitus (IDDM) and 8 with non-insulin-dependent diabetes mellitus, mean age 37.1 yr (range 25-64 yr), underwent glucose-clamp studies at diagnosis of diabetes at plasma glucose 200 mg/dl. Each subject was then treated twice daily with insulin for 6 mo with improvement in glycemic control, and the glucose-clamp studies repeated. Changes in glucose uptake at an insulin infusion rate of 1.0 mU X kg-1 X min-1 varied greatly from diagnosis to 6 mo. There were significant negative correlations between change in glucose uptake and diabetes type (r = -.78, P less than .002), C-peptide secretion (r = -.66, P less than .05), and age (r = -.62, P less than .05). At an insulin infusion rate of 10 mU X kg-1 X min-1 there was improvement in glucose uptake from diagnosis to 6 mo that did not reach statistical significance. During the steady-state periods of the glucose-clamp studies at diagnosis, growth hormone (GH) rose above basal, which reached statistical significance at the higher insulin infusion rate. This increase in GH was not apparent at the time of the glucose-clamp studies after insulin therapy. Our results indicate that in the clinical situation, only patients with IDDM can expect an improvement in their sensitivity to physiologic insulin levels with long-term insulin therapy. In all subjects, improvement in glycemic control leads to abolition of GH secretion in the presence of hyperglycemia.     

Comparison of an insulin analog,insulin aspart,and regular human insulin with no insulin in gestational diabetes mellitus

OBJECTIVE: To assess the short-term efficacy of insulin aspart in comparison with regular human insulin in women with gestational diabetes mellitus (GDM) during standardized meal tests. RESEARCH DESIGN AND METHODS: The study included 15 women with GDM who had inadequate diabetes control with diet alone. On 3 consecutive days, breakfast meal tests were performed-the first with no exogenous insulin and the other two after the injection of either regular insulin or insulin aspart. RESULTS: The peak insulin concentration was higher and the peak glucose and C-peptide concentrations were lower with both insulin preparations than with no exogenous insulin. Glucose areas under the curve above baseline were significantly lower with insulin aspart (180-min area, 7.1 mg. h. dl(-1); P = 0.018), but not with regular insulin (30.2 mg. h. dl(-1); P = 0.997), than with no insulin (29.4 mg. h. dl(-1)). CONCLUSIONS: This study demonstrates that effective postprandial glycemic control in women with GDM who required insulin was brought about by insulin aspart through higher insulin peak and lower demand on endogenous insulin secretion.     

Intensive insulin therapy with insulin lispro: a randomized trial of continuous subcutaneous insulin infusion versus multiple daily insulin injection

OBJECTIVE: To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin. RESEARCH DESIGN AND METHODS: This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA(1c) level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire. RESULTS: A significant decrease in HbA(1c) from baseline was shown for both groups. However, the overall treatment effect (CSII - MDI) for HbA(1c) was +0.08% (95% CI -0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of +/-0.5% (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales. CONCLUSIONS: No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than +/-0.5% HbA(1c) between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.     

Human insulin

Human insulin may be advantageous for certain subsets of patients, such as those with gestational diabetes and those who need insulin only during stress or surgery. To date, there is no evidence to support the use of human insulin in diabetics who are doing well on older insulin preparations.