果糖注射液对胸外科术后患者血糖和胰岛素的影响及安全性的临床研究

目的 比较果糖注射液(商品名:丰海能)和葡萄糖注射液对胸外科术后患者血糖和胰岛素的影响及安全性.方法 前瞻性单盲随机对照研究.选取胸外科临床有效病例60例,于手术当天至术后第6天静脉滴注10%果糖注射液(试验组)或10%葡萄糖注射液(对照组),750ml/d,3h内输注完,连用7d.观察患者用药前和用药中血糖和胰岛素水平的变化情况,比较两组之间的差别.同时观察用药前后血尿酸、尿素氮、肝肾功能、心电图等变化以及不良反应的发生情况.结果 试验组输液前后血糖变化值为(0.64±1.98)mmol/L,对照组输液前后血糖变化值为(4.13±1.63)mmol/L,对应试验组比较差异有统计学意义(P＜0.05).试验组用药中对血胰岛素影响亦较小(0.82±9.76)mmol/L,对照组该指标明显升高(8.35±8.55)mmol/L,组间比较差异有统计学意义(P＜0.05).用药后两组患者均未发现血尿酸、尿素升高,肝肾功能和心电图等指标无明显异常变化,未出现不良反应.结论 适量静脉输注果糖注射液对胸外科术后患者血糖和胰岛素的影响较小,有较好的安全性.     

早期短程胰岛素强化治疗新诊断2型糖尿病的临床观察

目的:观察短期胰岛素强化治疗初诊的2型糖尿病患者的疗效.方法:将新诊断的2型糖尿病患者70例随机分为两组,治疗组35例予胰岛素强化治疗,对照组35例给予口服降糖药物治疗,比较两组治疗前后空腹血糖(FPG).餐后2 h血糖(2hPG).糖化血红蛋白(HbAlc).空腹胰岛素(FINS).胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-β).结果:治疗后两组的血糖均下降,且控制在理想水平,但治疗组血糖达标时间较对照组明显快,差异有显著性(P＜0.05);两组胰岛β细胞功能指数均有改善,但治疗组较对照组改善明显,治疗组FINS.HOMA-β功能指数较对照组升高明显,差异有显著性(P＜0.05).结论:短期胰岛素强化治疗可更快速控制血糖达理想目标,显著改善胰岛β细胞分泌功能,比常规口服降糖药物更具优势.     

术前口服碳水化合物对胃癌术后胰岛素抵抗影响的机制研究

目的 评价胃癌患者术前口服碳水化合物对术后胰岛素抵抗的影响并探讨其可能机制.方法 将2011年4-10月连续入院且符合入组标准的60例胃癌患者按照随机双盲原则分为口服碳水化合物组和口服安慰剂组,术前4h监测患者静息能量消耗(REE)及呼吸商,并抽取空腹血,测定血糖、胰岛素及三酰甘油,麻醉前2～3h口服500 ml碳水化合物(或安慰剂),2组患者均在硬膜外加静脉复合全身麻醉下行根治性远端胃癌切除术,开腹即刻及关腹前取腹直肌组织并固定,术后即刻抽血测定血糖、胰岛素及三酰甘油,并监测术后REE及呼吸商,比较2组患者手术前后胰岛素抵抗指数、三酰甘油、REE及呼吸商的变化,透射电镜观察2组患者腹直肌线粒体超微结构变化.结果 共48例患者完成试验(口服碳水化合物组和口服安慰剂组各24例),口服安慰剂组和口服碳水化合物组术后胰岛素抵抗指数分别为12.68±3.13和5.67±1.40(t=6.646,P=0.003);静息能量分别为(1458±169)、(1341±110) kcal/d(t=2.851,P=0.046);呼吸商分别为0.73 ±0.42和0.79 ±0.22(t=6.546,P=0.041);血三酰甘油水平分别为(0.53±0.24)、(1.04±0.97)g/L(t =2.542,P=0.006);腹直肌线粒体损伤指数分别为1.14 ±0.33和0.92 ±0.19(t =2.730,P=0.028),差异均有统计学意义.口服安慰剂组术后线粒体较术前明显肿胀,嵴膜不清晰.结论 术前口服碳水化合物可降低胃癌根治术患者术后胰岛素抵抗,减少静息能量消耗,改善物质代谢;可能机制与口服碳水化合物促进胰岛素释放,保护线粒体功能有关.     

维持性血液透析患者血脂变化和胰岛素抵抗的相关分析

目的 通过对48例维持性血液透析患者空腹血糖、血清胰岛素和血脂各项指标的观察,计算胰岛素抵抗指数和胰岛素敏感指数,评价胰岛素抵抗情况.方法 选取我科维持性血液透析患者48例(观察组),同时选取30名健康体检者(对照组)作为正常对照,测定两组受试者的血糖、糖化血红蛋白、血清胰岛素、尿素氮、肌酐、尿酸、血脂指标,计算胰岛素抵抗指数和胰岛素敏感指数.结果 维持性血液透析患者的血糖、血清胰岛素、糖化血红蛋白、胰岛素抵抗指数水平升高,胆固醇、高密度脂蛋白、低密度脂蛋白与对照组比较差异有统计学意义(P＜0.05),其中胆固醇与血糖呈负相关(r=-0.3482,P＜0.05);高密度脂蛋白与血清胰岛素呈负相关(r=-0.2603,P＜0.05);低密度脂蛋白与血糖呈负相关(r=-0.3289,P＜0.05),而对照组仅甘油三酯与血糖、胰岛素抵抗指数呈正相关(r分别=0.371,0.368,P均＜0.05).结论 维持性血液透析患者中存在脂代谢紊乱,可能参与胰岛素抵抗.     

胰岛素强化治疗对严重创伤患者炎性反应及预后的影响

目的 了解胰岛素强化治疗对严重创伤患者炎性反应及预后的影响.方法 将80例严重创伤患者按随机配对原则分为治疗组(40例)和对照组(40例).治疗组患者入院后立即行胰岛素强化治疗,从胰岛素泵泵入胰岛素2～4 U/h,控制血糖值在6～8 mmol/L;对照组按临床常规治疗,不给予胰岛素.观察2组患者的发热、器官损伤情况,统计病死率.于开始治疗后1、3、5、7 d晨抽取2组患者静脉血,检测血浆TNF-α、IL-2、IL-10、C反应蛋白(CRP)水平.结果 治疗组患者9例发生高热,低于对照组(29例).治疗组和对照组各有31例和30例患者出现1个脏器功能不全.治疗组和对照组同一患者出现3个脏器功能不全的分别为10、19例,出现4个脏器功能不全的分别为7、12例.治疗组伤后3 d内死亡4例,3 d以后死亡1例,病死率为12.5%;对照组伤后3 d内死亡5例,3 d以后死亡4例,病死率为22.5%.治疗后3～7 d,治疗组患者TNF-α、CRP值均低于对照组(P<0.05或P<0.01),而IL-2、IL-10值则均高于对照组(P<0.05或P<0.01).治疗后7 d,治疗组TNF-α、CRP值最低,分别为(1.3±0.6)μg/L、(55±16)mg/L,且明显低于对照组的(3.0±0.8)μg/L、(89±20)mg/L(P<0.01).结论 严重创伤后行胰岛素强化治疗,可以减轻患者全身性炎性反应程度,改善创伤患者预后.     

胰岛素强化治疗对胃癌手术患者临床结局的影响

目的 研究胰岛素强化治疗对胃癌手术患者临床结局的影响.方法 46例胃癌手术患者随机分为术后胰岛素强化治疗组(n=23,血糖控制在4.4～6.1 mmool/L)和常规治疗组(n=23,血糖控制在10.0～11.1 mmol/L).动态监测比较两组围手术期空腹血糖(FBG)、空腹胰岛素定量(FINS)、白细胞介素-6(IL-6)、肿瘤坏死因子-α[(TNF-α)及C-反应蛋白(CRP)水平,并根据稳态模式评估法(HOMA)计算胰岛素抵抗指数(HOMA-IR);记录两组患者术后并发症发生情况.结果 两组患者均无低血糖发生,胰岛素强化治疗组术后发热天数、抗生素使用天数、住院天数及并发症发生率均明显低于常规治疗组(P＜0.05);强化治疗组术后1 d、3 d血清InHOMA-IR、IL-6、TNF-α及术后1、3、7 d的CRP均明显低于常规治疗组(P＜0.05).结论 胰岛素强化治疗可拮抗术后机体的高炎状态,抗炎效应可能是胰岛素强化治疗又一改善手术创伤患者预后的重要机制.     

脂连素对大鼠创伤后胰岛素抵抗的作用

目的　观察创伤后胰岛素抵抗现象,探讨脂连素对手术创伤导致的胰岛素抵抗的作用和机制.方法　60只SD大鼠随机分为脂连素组(n=20)、创伤组(n=20)以及对照组(n=20).建立大鼠创伤模型,脂连索组运用脂连素进行预处理(1 mg/kg腹腔内注射),测定大鼠的血糖及血清胰岛素浓度,计算胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-β);检测骨骼肌胰岛素受体底物蛋白-1( IRS-1)、蛋白激酶B(PKB/Akt)的含量及其磷酸化状态.结果　创伤组与对照组比较血糖浓度明显升高(P＜0.05),血清胰岛素浓度先短暂下降然后逐渐升高(P＜0.05).HOMA-IR明显高于对照组(P＜0.05),HOMA-β则低于对照组(P＜0.05).脂连素组大鼠血糖浓度明显下降(P＜0.05),血清胰岛素浓度无明显改变(P＞0.05).HOMA-IR明显下降(P＜0.05),HOMA-β明显上升(P＜0.05).创伤组与对照组、脂连素组与创伤组大鼠骨骼肌中总的IRS-1及PKB/Akt蛋白含量无明显差异,但创伤组较对照组大鼠骨骼肌的IRS-1酪氨酸(Tyr)位点的磷酸化水平下降了31％[ (88.54±33.48)比(128.60±33.19),F=0.108,P＜0.01],丝氨酸(Ser)位点磷酸化水平增加了64％[(154.31±36.94)比(94.20±27.88),F=0.602,P＜0.01],PKB/Akt的磷酸化水平下降了46％[ (46.58±2.48)比(86.32±3.31),F=0.153,P＜0.01].脂连素组大鼠的骨骼肌IRS-1 Tyr位点的磷酸化水平较创伤组上升了23％[(109.05±30.77)比(88.54±33.48),F=0.012,P＜0.01],而Ser位点磷酸化水平下降了30％ [(118.65±33.49)比(154.31±36.94),F=0.272,P＜0.01],PKB/Akt的磷酸化水平上升了56％[ (72.73±2.95)比(46.58±2.48),F=0.473,P＜0.01].结论 大鼠创伤后存在胰岛素抵抗现象,其机制与胰岛素受体后信号转导通路受阻有关.脂连素能缓解创伤后胰岛素抵抗途径的发生和发展,从而改善创伤后胰岛索抵抗产生的高血糖.     

氯沙坦对非糖尿病维持性血液透析患者血清脂联素及胰岛素抵抗的影响

目的 探讨氯沙坦对非糖尿病维持性血液透析患者血清脂联素水平和胰岛素抵抗的影响,及非糖尿病维持性血液透析患者血清脂联素与胰岛素抵抗的相关性.方法 测定62例非糖尿病维持性血液透析患者和30名健康对照者的血清胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、白蛋白、尿素氮、肌酐、C反应蛋白、收缩压、舒张压、血清脂联素、血糖、胰岛素,并计算稳态模型胰岛素抵抗指数及胰岛素敏感指数.分析血清脂联素与胰岛素抵抗等指标的相关性.将维持性血液透析患者按随机数字表法分为氯沙坦组(31例)和非氯沙坦组(31例),氯沙坦组给予口服氯沙坦每天50～100 mg,共6个月,测定治疗前、后两组血清脂联素、血糖、胰岛素及计算稳态模型胰岛素抵抗指数及胰岛素敏感指数.结果 维持性血液透析组患者甘油三酯、尿素氮、肌酐、C反应蛋白、血清脂联素、胰岛素、胰岛素抵抗指数、收缩压、舒张压水平与健康对照组比较差异有统计学意义(P分别＜ 0.01,＜0.05);而维持性血液透析组患者高密度脂蛋白及白蛋白水平与健康对照组比较差异也有统计学意义(P＜0.05).氯沙坦治疗组患者血清脂联素和胰岛素抵抗较治疗前比较差异也有统计学意义(P均＜ 0.01).相关分析显示血清脂联素、胰岛素、胰岛素抵抗指数、C反应蛋白、甘油三酯呈负相关(r分别为-0.282,- 0.362,- 0.411,-0.307,P分别＜0.05,＜0.01),血清脂联素与胰岛素敏感指数、胆固醇、高密度脂蛋白呈显著正相关(r分别为0.61、0.249、0.396,P分别＜0.05,＜0.01).结论 氯沙坦可使非糖尿病维持性血液透析患者血清脂联素升高,并减轻维持性血液透析患者高胰岛素血症和胰岛素抵抗.     

糖尿病足溃疡患者创面局部注射胰岛素对全身血糖及创面的影响

目的 观察糖尿病足溃疡患者创面局部注射胰岛素对全身血糖和创面肉芽组织形成的影响. 方法 选择2009年6月-2010年6月在笔者单位住院治疗的糖尿病足患者32例,按随机数字表法分为胰岛素组和对照组,每组16例.所有患者预先清创.(1)胰岛素组:将胰岛素计算剂量的1/2用生理盐水稀释成1 mL后,浸润注射于溃疡创面基底部,另1/2计算量按常规行腹部皮下注射,均为2次/d.(2)对照组:将胰岛素计算剂量的全量常规注射于腹部皮下,溃疡创面基底部浸润注射1 mL生理盐水,均为2次/d.2组患者均连续注射7d.于患者每次注射前及注射后0.5、1.0、2.0、4.0 h,分别检测其空腹血糖值.于首次注射前及注射3、5、7 d,评估创面肉芽组织生长程度;取创面组织标本观察CD34表达情况,据此计算创面微血管密度(MVD).对实验数据行t检验.结果 2组患者观察期内空腹血糖值维持在6.6～12.8(10.0±2.2)mmol/L,各时相点组间比较,差异均无统计学意义(t值为0.000～2.209,P值均大于0.05).注射第5天起,胰岛素组患者局部创面肉芽组织明显增多;第7天达生长高峰[(59.06±1.58％],与对照组[(23.61±1.57)％]比较,差异有统计学意义(t=17.420,P=0.0.000).CD34表达情况显示,胰岛素组注射3 d起有新生血管形成,但此时MVD与对照组接近(t=0.0247,P＞0.05);注射5、7d,胰岛素组创面组织MVD每200倍视野中分别为(8.34±0.48)、(11.22±0.97)个,明显多于对照组的(4.42±0.14)、(5.44±1.13)个,t值分别为16.568、27.664,P值均小于0.01. 结论 糖尿病足溃疡患者创面局部注射胰岛素对全身血糖有较明显影响,能加速肉芽组织生长,促进创面愈合.     

结直肠癌代谢紊乱与胰岛素抵抗的研究

目的 探讨结直肠癌患者是否存在胰岛素抵抗及其临床意义.方法 前瞻性收集2007年6月至2010年6月间温州医学院附属第三医院135例结直肠癌患者作为结直肠癌组,选择同期进行查体的120名健康人为对照组,测量身高、体质量、血压,抽空腹血测量血糖、三酰甘油、HDL-C和胰岛素,计算胰岛素抵抗指数（lnHOMA-IR）.结果 结直肠癌组和对照组胰岛素抵抗指数分别为0.84±0.38和0.42±0.08,代谢综合征发生率分别为34.1%（46/135）和22.5%（27/120）,差异均有统计学意义（P＜0.05）.结直肠癌代谢综合征与非代谢综合征患者的胰岛素抵抗指数分别为0.98±0.41和0.74±0.22,差异无统计学意义（P＞0.05）.胰岛素抵抗指数与结直肠癌分化程度、浸润深度、淋巴结转移、远处转移及TNM分期均无关（P＞0.05）.结论 结直肠癌患者存在胰岛素抵抗,原因可能与代谢综合征及肿瘤本身有关.     

Desensitization of insulin secretion by depolarizing insulin secretagogues

Prolonged stimulation of insulin secretion by depolarization and Ca2+ influx regularly leads to a reversible state of decreased secretory responsiveness to nutrient and nonnutrient stimuli. This state is termed "desensitization." The onset of desensitization may occur within 1 h of exposure to depolarizing stimuli. Desensitization by exposure to sulfonylureas, imidazolines, or quinine produces a marked cross-desensitization against other ATP-sensitive K+ channel (KATP channel)-blocking secretagogues. However, desensitized beta-cells do not necessarily show changes in KATP channel activity or Ca2+ handling. Care has to be taken to distinguish desensitization-induced changes in signaling from effects due to the persisting presence of secretagogues. The desensitization by depolarizing secretagogues is mostly accompanied by a reduced content of immunoreactive insulin and a marked reduction of secretory granules in the beta-cells. In vitro recovery from a desensitization by the imidazoline efaroxan was nearly complete after 4 h. At this time point the depletion of the granule content was partially reversed. Apparently, recovery from desensitization affects the whole lifespan of a granule from biogenesis to exocytosis. There is, however, no direct relation between the beta-cell granule content and the secretory responsiveness. Even though a prolonged exposure of isolated islets to depolarizing secretagogues is often associated with the occurrence of ultrastructural damage to beta-cells, we could not find a cogent link between depolarization and Ca2+ influx and apoptotic or necrotic beta-cell death.     

4种注射部位及2种拔针方式注射胰岛素针尖溢液比较

目的减少糖尿病患者注射胰岛素针尖溢液发生率及程度。方法选择41例注射胰岛素的糖尿病患者,采用自身对照法于腹部、上臂三角肌下缘、大腿外侧、臀部外上侧注射相同剂量的胰岛素,注射胰岛素完毕针头均在局部停留15 s拔针,其中方法 A直接拔针,方法 B退出少许针头停留2 s后再拔针,观察拔针后胰岛素针尖溢液情况。结果方法 A注射164例次,针尖溢液115例次;方法 B注射164例次,针尖溢液87例次,两法针尖溢液率比较,差异有统计学意义(P 0. 01)。同一种拔针方式下,不同注射部位针尖溢液程度存在统计学差异(均P 0. 01),其中以腹部注射针尖溢液最少,臀部外上侧注射针尖溢液最多;不同拔针方式下,同一注射部位不同拔针方式的针尖溢液程度存在统计学差异(P 0. 05,P 0. 01)。结论合理轮换胰岛素注射部位,可选择腹部注射并采用退出少许针头停留2 s后再拔针,可减少胰岛素针尖溢液量。     

The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus

We have studied the effects of 3 wk of continuous subcutaneous insulin infusion (CSII) on endogenous insulin secretion and action in a group of 14 type II diabetic subjects with a mean (+/-SEM) fasting glucose level of 286 +/- 17 mg/dl. Normal basal and postprandial glucose levels were achieved during insulin therapy at the expense of marked peripheral hyperinsulinemia. During the week of posttreatment evaluation, the subjects maintained a mean fasting glucose level of 155 +/- 11 mg/dl off insulin therapy, indicating a persistent improvement in carbohydrate homeostasis. Adipocyte insulin binding and in vivo insulin dose-response curves for glucose disposal using the euglycemic clamp technique were measured before and after therapy to assess the effect on receptor and postreceptor insulin action. Adipocyte insulin binding did not change. The insulin dose-response curve for overall glucose disposal remained right-shifted compared with age-matched controls, but the mean maximal glucose disposal rate increased by 74% from 160 +/- 14 to 278 +/- 18 mg/m2/min (P less than 0.0005). The effect of insulin treatment on basal hepatic glucose output was also assessed; the mean rate was initially elevated at 159 +/- 8 mg/m2/min but fell to 90 +/- 5 mg/m2/min in the posttreatment period (P less than 0.001), a value similar to that in control subjects. Endogenous insulin secretion was assessed in detail and found to be improved after exogenous insulin therapy. Mean 24-h integrated serum insulin and C-peptide concentrations were increased from 21,377 +/- 2766 to 35,584 +/- 4549 microU/ml/min (P less than 0.01) and from 1653 +/- 215 to 2112 +/- 188 pmol/ml/min (P less than 0.05), respectively, despite lower glycemia. Second-phase insulin response to an intravenous (i.v.) glucose challenge was enhanced from 170 +/- 53 to 1022 +/- 376 microU/ml/min (P less than 0.025), although first-phase response remained minimal. Finally, the mean insulin and C-peptide responses to an i.v. glucagon pulse were unchanged in the posttreatment period, but when glucose levels were increased by exogenous glucose infusion to approximate the levels observed before therapy and the glucagon pulse repeated, responses were markedly enhanced. Simple and multivariate correlation analysis showed that only measures of basal hepatic glucose output and the magnitude of the postbinding defect in the untreated state could be related to the respective fasting glucose levels in individual subjects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Role of insulin and insulin resistance in androgen excess disorders

Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events. Among the several metabolic and growth-promoting effects of insulin, insulin resistance is defined as an attenuated effect of insulin on glucose metabolism, primarily the limited export of blood glucose into skeletal muscle and adipose tissue. On the other hand, not all the signaling pathways and insulin-responsive tissues are equally affected, and some effects other than the metabolic actions of insulin are overexpressed. Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion. Polycystic ovary syndrome (PCOS) is the most common form of androgen excess disorder (AED), and its pathogenesis is closely associated with insulin resistance. Patients with idiopathic hirsutism also exhibit insulin resistance, albeit lower than patients with PCOS. Although it is not as evident as in PCOS, patients with congenital adrenal hyperplasia may have insulin resistance, which may be further exacerbated with glucocorticoid overtreatment and obesity. Among patients with severe insulin resistance syndromes, irrespective of the type of disease, hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins. It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs, including PCOS. It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance. Instead, the treatment decision should be based on the constellation of the signs, symptoms and presence of obesity; acanthosis nigricans; and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.     

The independence of insulin release and ambient insulin in vitro

The effect of insulin on its own secretion was tested in three independent experimental models using insulin concentrations that approached physiologic values. The collected secretions from glucose-stimulated islet tissue had no effect on insulin release from other islets. Perifused insulin had no effect on the release of endogenous insulin even when the assay was completely controlled for dilutional effects. Perifused insulin had no effect on the release of prelabeled insulin from glucose-stimulated islets. Similarly, proinsulin did not affect insulin release. Porcine insulin did not affect the function of porcine or canine islets. These studies strongly support the independence of glucose-stimulated insulin secretion and ambient insulin.     

Pulsatile insulin secretion dictates systemic insulin delivery by regulating hepatic insulin extraction in humans

In health, insulin is secreted in discrete pulses into the portal vein, and the regulation of the rate of insulin secretion is accomplished by modulation of insulin pulse mass. Several lines of evidence suggest that the pattern of insulin delivery by the pancreas determines hepatic insulin clearance. In previous large animal studies, the amplitude of insulin pulses was related to the extent of insulin clearance. In humans (and in large animals), the amplitude of insulin oscillations is approximately 100-fold higher in the portal vein than in the systemic circulation, despite only a fivefold dilution, implying preferential hepatic extraction of insulin pulses. In the present study, by direct hepatic vein sampling in healthy humans, we sought to establish the extent of first-pass hepatic insulin extraction and to determine whether the pattern of insulin secretion (insulin pulse mass and amplitude) dictates the hepatic insulin clearance and thereby delivery of insulin to extrahepatic insulin-responsive tissues. Five nondiabetic subjects (two men and three women, mean age 32 years [range 25-39], BMI 24.9 kg/m(2) [21.2-27.1]) participated. Insulin and C-peptide delivery from the splanchnic bed was measured in basal overnight-fasted state and during a glucose infusion of 2 mg . kg(-1) . min(-1) by simultaneous sampling from the hepatic vein and an arterialized vein along with direct estimation of splanchnic blood flow. Fractional insulin extraction was calculated from the difference between the C-peptide and insulin delivery rates from the liver. The time patterns of insulin concentrations and hepatic insulin clearance were analyzed by deconvolution and Cluster analysis, respectively. Cross-correlation analysis was used to relate C-peptide secretion and insulin clearance. Glucose infusion increased peripheral glucose concentrations from 5.4 +/- 0.1 to 6.4 +/- 0.4 mmol/l (P < 0.05). Likewise, insulin and C-peptide concentrations increased during glucose infusion (P < 0.05). Hepatic insulin clearance increased with glucose infusion (1.06 +/- 0.18 vs. 2.55 +/- 0.38 pmol . kg(-1) . min(-1); P < 0.01), but fractional hepatic insulin clearance was stable (78.2 +/- 4.4 vs. 84 0. +/- 3.9%, respectively; P = 0.18). Insulin secretory-burst mass rose during glucose infusion (P < 0.05), whereas the interburst interval remained unchanged (4.4 +/- 0.2 vs. 4.5 +/- 0.3 min; P = 0.36). Cluster analysis identified an oscillatory pattern in insulin clearance, with peaks occurring approximately every 5 min. Cross-correlation analysis between prehepatic C-peptide secretion and hepatic insulin clearance demonstrated a significant positive association without detectable (<1 min) time lag. Insulin secretory-burst mass strongly predicted insulin clearance (r = 0.81, P = 0.0043). In conclusion, in humans, approximately 80% of insulin is extracted during the first liver passage. The liver rapidly responds to fluctuations in insulin secretion, preferentially extracting insulin delivered in pulses. The mass (and therefore amplitude) of insulin pulses traversing the liver is the predominant determinant of hepatic insulin clearance. Therefore, through this means, the pulse mass of insulin release dictates both hepatic (directly) as well as extra-hepatic (indirectly) insulin delivery. These findings emphasize the dual role of the liver and pancreas and their relationship mediated through magnitude of insulin pulse mass in regulating the quantity and pattern of systemic insulin delivery.     

胰岛素强化治疗对胃癌术后胰岛素抵抗的初步观察

目的探讨胰岛素强化治疗对胃癌患者术后胰岛素抵抗（IR）的影响。方法将22例胃癌患者随机分为胰岛素强化治疗组和对照组各11例，均在硬膜外麻醉下行根治性远端胃次全切除术，分别于术前和术后第1、3、7天测量空腹血糖（FBG）、胰岛素（FINS）、C-反应蛋白（CRP），使用稳态模式评估法（homeostasis model assessment，HOMA）计算胰岛素抵抗指数（HOMA—IR），利用多元相关分析法分析术后HOMA—IR的相关因素。结果胰岛素强化治疗能明显降低胃癌术后患者的FBG、FINS、lnHOMA—IR（FBG、lnHOMA—IRP〈0．01，FINSP〈0．05）及IR发生率；强化治疗组患者术后CRP水平明显低于对照组（P〈0．05）；lnHOMA—IR与体重指数（BMI）、FINS高度正相关（P〈0．01）。结论胰岛素强化治疗能降低胃癌术后患者的胰岛素抵抗，减轻患者术后的炎性反应。     

Patterns of exogenous insulin requirement reflect insulin sensitivity changes in trauma

INTRODUCTION: We investigated patterns of blood glucose and exogenous insulin requirement in the intensive care unit, and questioned whether they reflect fluctuations in insulin activity. METHODS: Records for burn intensive care unit patients with 7 days of glucose control with insulin were reviewed. Hourly blood glucose and insulin dose were matched for time collected and analyzed with linear and cosine regression. Frequency analysis identified recurring patterns. RESULTS: Diurnal patterns of blood glucose and insulin requirement were noted (insulin troughs = noon; insulin peaks = midnight; glucose troughs = 5 am; glucose peaks = 5 pm). Average insulin requirement increased at a constant linear rate (slope = .013, r2 = .57, P < or = .001). CONCLUSIONS: Diurnal patterns in blood glucose and insulin requirement mirror those of healthy subjects and may reflect persistence of normal variability in insulin activity. The 5-hour offset in peaks and troughs is suggestive of complex interplay between insulin availability and receptor sensitivity. The insulin requirement to blood glucose ratio increased, evidence that insulin resistance progresses over time.