参附注射液对大鼠胰腺移植受体小肠肠粘膜屏障的保护作用

目的探讨参附注射液(SF)对大鼠胰腺移植受体肠粘膜屏障的保护作用及机制。方法24只糖尿病大鼠随机分为缺血再灌注组(IR组,n=12),参附注射液预处理组(SF组,n=12),12只正常大鼠为对照组,IR组和SF组大鼠均接受胰腺移植,再灌注后5d检测小肠通透性和吸收功能,检测血清TNF-α、NO、SOD和淀粉酶活性,取受体空肠粘膜组织检测小肠粘膜粘膜湿重、微绒毛高度及宽度、MDA含量及MPO活性,同时取肠系膜静脉血、肠系膜淋巴结、肝及脾组织进行细菌培养,观察细菌易位情况。结果再灌注后SF组血清TNF-α含量(P<0.01)、淀粉酶活性(P<0.01)、MDA含量(P<0.01)、MPO活性(P<0.01)、小肠通透性(P<0.01)、细菌易位率(P<0.01)和小肠粘膜损伤程度均低于IR组;血清NO和SOD含量、小肠吸收功能均高于IR组(P<0.01)。结论SF预处理可保护大鼠胰腺移植受体小肠肠粘膜屏障,降低细菌易位率,机制可能与降低胰酶活性、减少TNF-α生成、减轻PMNs粘附与聚集、增加NO和SOD含量有关。     

静脉补铁对维持性血液透析患者微炎症及氧化应激状态的影响

目的探讨静脉补铁对维持性血液透析(MHD)患者微炎症及氧化应激状态的影响。方法选择MHD患者71例,随机分为静脉组(24例)、口服组(27例)和未补铁组(20例)。观察用药前后血红蛋白(Hb)浓度、红细胞压积(Hct)、血清铁(SI)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)等疗效指标以及血清C反应蛋白(CRP)、白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)等炎症指标和血浆及红细胞中丙二醛(MDA)、过氧化物歧化酶(SOD)、谷胱苷肽过氧化物酶(CSH-px)、全血过氧化氢酶(CAT)等氧化应激指标,并监测不良反应。结果8周后,静脉组Hb水平及SF较治疗前明显改善(P<0.01);血浆及红细胞中MDA较治疗前显著升高(P<0.01),SOD、GSH-px和全血中的CAT均较治疗前显著降低(P<0.01或P<0.05);血清CRP、IL-1β、TNF-α均较治疗前显著升高(P<0.01或P<0.05)。相关性分析发现,8周后静脉组血浆MDA与SF呈正相关,MDA与TNF-α呈正相关(P<0.01)。结论静脉补铁可有效改善患者贫血及缺铁,但也加剧了其炎症及氧化应激状态。MHD患者体内炎症及氧化应激之间具有相关性,氧化应激似乎是形成慢性炎症的关键因素之一。     

急性腹腔感染与胰岛素抵抗关系及炎症因子作用时间“窗”

目的 探讨急性腹腔感染大鼠早期葡萄糖代谢与炎症因子水平的关系.方法 SD大鼠随机分为4组:A组,盲肠结扎穿孔(CLP)组;B组,腹腔脂多糖(LPS)注射组;C组,CLP加LPS注射组;D组,对照组.A,B,C组均为急性腹腔感染模型.检测各组血浆中不同时间点葡萄糖、胰岛素、肿瘤坏死因子a(TNF-α)、白细胞介素6(IL-6)的水平.HOMA法计算胰岛素抵抗指数(IRI),以此评价胰岛素抵抗(IR)程度.结果 大鼠急性腹腔感染组(A、B、C组)早期血浆中葡萄糖水平及IRI升高,6 h达峰值.IPd变化与TNF-α,IL-6水平的对数值之间呈正相关(r=0.609和0.755).接受LPS注射者(B、C组)IL-6升高较未接受LPS注射组(A组)升高明显.IL-6较TNF-α维持时间延长.结论 急性腹腔感染早期可出现IR;TNF-α和IL-6与IR的程度呈正相关,不同感染模型的炎症因子水平变化存在差异,其作用时间"窗"不同.     

参附注射液对肠缺血-再灌注大鼠肿瘤坏死因子α的影响

目的观察肿瘤坏死因子α(TNF-α)在大鼠肠缺血-再灌注损伤过程中的作用及参附注射液对TNF-α的影响,探讨参附注射液防治肠缺血-再灌注损伤机制。方法 SD大鼠随机分为肠缺血-再灌注组(IR组)、参附注射液预处理组(SF组)和假手术组(C组)。采用阻断肠系膜上动脉(SMA)的方法制造肠缺血-再灌注模型。分别测定各组动物血浆、肠组织TNF-α含量及血液动力学变化;光镜观察肠粘膜损伤情况。结果IR组再灌注后MAP下降,与C组和SF组比有显著性差异(P<0.01);SF组肠粘膜损伤程度减轻,与IR组比有显著性差异(P<0.01);SF组血浆及肠组织TNF-α水平降低,与IR组比有显著性差异(P<0.01)。结论参附注射液可明显防治大鼠肠缺血-再灌注导致的肠粘膜损伤,这种作用可能是通过抑制TNF-α的释放实现的。     

妊娠糖尿病患者外周血细胞焦亡相关因子的表达及与胰岛素抵抗的关系

目的探讨妊娠期糖尿病(gestational diabetes mellitus, GDM)患者血清细胞焦亡相关因子半胱氨酸蛋白酶-1(caspase-1)、白介素-18(IL-18)水平及其与胰岛素抵抗(IR)的关系。方法选取2019年4月至2021年3月开封市中医院收治的GDM患者102例为GDM组, 纳入同期产检健康孕妇102例为正常组。比较GDM组与正常组孕妇年龄、孕周、空腹胰岛素(FINS)、孕前体重指数(BMI)、甘油三酯(TG)、空腹血糖(FBG)、总胆固醇(TC)、稳态模型胰岛素抵抗指数(HOMA-IR)等资料;酶联免疫吸附法(ELISA)检测血清caspase-1、IL-18水平;Pearson法分析GDM患者血清caspase-1、IL-18水平与HOMA-IR的相关性;Logistic回归法分析GDM发生的影响因素。结果 GDM组患者TG [(2.94±0.99)mmol/L vs(2.09±0.70)mmol/L]、FBG [(5.87±1.94)mmol/L vs(4.90±1.67)mmol/L]、TC [(5.72±1.92)mmol/L vs(5.03±...     

妊娠期糖尿病患者血清α-亚麻酸与血糖水平的关系

目的检测妊娠期糖尿病(GDM)患者血清α-亚麻酸(ALA)水平,并探讨其与血糖代谢的关系。方法选取2018年3月至2019年3月本院收治的116例孕妇(孕24～32周)为研究对象,根据GDM诊断标准将其中58例GDM孕妇纳入GDM组,58例正常妊娠孕妇为对照组。比较两组研究对象血清中ALA、血糖水平及相关指标,分析GDM孕妇血清中ALA与血糖指标的相关性,采用多元回归分析GDM的影响因素。结果 (1)与对照组比较,GDM组孕妇血清ALA水平显著降低,而空腹血糖(FPG)、餐后1 h血糖(1hPG)、2hPG、空腹胰岛素(FINS)水平及胰岛素抵抗指数(HOMA-IR)显著升高(P均0.05);(2)GDM组孕妇血清中ALA水平与FPG、1hPG、2hPG、FINS水平及HOMA-IR均呈显著负相关(P0.05);(3)多元回归分析显示,糖尿病家族史、ALA是GDM的危险因素;(4)ROC曲线分析显示,ALA诊断GDM的最佳截断值为1.73μg/ml,曲线下面积为0.790,敏感度为70.7%,特异度为77.6%。结论 GDM患者血清中ALA水平明显降低,且其水平与各血糖指标呈负相关,提示ALA参与GDM的发生过程。     

异氟醚预处理对大鼠肝脏缺血再灌注损伤的影响

目的 探讨异氟醚预处理对大鼠肝脏缺血再灌注损伤的影响.方法 成年雄性SD大鼠24只,体重180～220 g,随机分为3组(n=8):假手术组(S组)吸人纯氧30 min,间隔30 min后仅开腹;肝脏缺血再灌注组(IR组)吸入纯氧30 min,间隔30 min后行肝脏缺血60 min,再灌注4 h;异氟醚预处理组(Iso组)吸入1.4%异氟醚30 min,间隔30 min后行肝脏缺血60 min,再灌注4 h.于再灌注4 h时处死大鼠,留取肝脏及腹主动脉血5ml.测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)浓度,血清及肝组织匀浆上清液中肿瘤坏死因子α(TNF-α)的浓度,肝组织髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,观察肝组织病理学改变.结果 与S组比较,IR组、Iso组血清ALT、AST和TNF-α水平明显升高,肝组织TNF-α含量升高,肝组织MPO活性升高,MDA含量升高,SOD活性降低(P＜0.05或0.01),肝组织病理损伤明显;与IR组比较,Iso组血清ALT、AST和TNF-α水平降低,肝组织TNF-α含量降低,肝组织MPO活性降低,MDA含量降低,SOD活性升高(P＜0.05或0.01),肝组织病理损伤程度减轻.结论 1.4%异氟醚预处理可明显减轻大鼠肝脏缺血再灌注损伤,其机制可能与抑制TNF-α的释放、减少中性粒细胞在肝组织的浸润有关.     

妊娠期糖尿病并发子痫前期患者胎盘组织抵抗素、人脂质运载蛋白及血糖脂代谢检测价值

目的分析妊娠期糖尿病(gestational diabetes mellitus, GDM)并发子痫前期(preeclampsia, PE)孕妇胎盘组织抵抗素、人脂质运载蛋白(lipid carrier protein, LCN)及血糖脂代谢检测价值, 为GDM并发子痫前期诊疗提供指导。方法收集2017年1月至2020年1月烟台市烟台山医院收治的GDM并发PE孕妇96例(GDM-PE组), 按2∶1比例选取单纯GDM孕妇(GDM组)与正常孕妇各48例(对照组), 免疫组化法测定胎盘组织抵抗素、LCN水平, 采血测定糖脂代谢水平, 比较各组妊娠结局, 分析抵抗素、LCN、糖脂代谢与GDM并发PE的关系。结果 GDM组、GMD-PE组空腹血糖(fasting blood-glucose, FBG)[(4.57±0.66)、(5.23±0.61)mmol/L]、空腹胰岛素(fasting insulin, FINS)[(11.97±1.5)、(15.12±3.52)mIU/L]高于对照组[(4.11±0.23)、(6.75±1.34)mIU/L(P<0.05)], GDM-PE组FBG...     

外周血NK细胞和细胞因子在妊娠期糖尿病患者中的表达及临床意义

目的 探讨外周血中NK细胞的水平与妊娠期糖尿病(GDM)发生发展的相关性。方法 选取2020年12月至2021年10月于中国人民解放军总医院第六医学中心妇产科确诊的30例GDM患者作为GDM组，另选择同期健康的40例孕妇作为对照组。通过流式细胞仪检测分析两组孕妇NK细胞占比及各亚群(CD3-CD56^brightNK细胞、CD3-CD56^dimNK细胞)分布，以及外周血细胞因子白细胞介素10(IL-10)、肿瘤坏死因子-α(TNF-α)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、干扰素-γ(IFN-γ)、穿孔素和颗粒酶B的水平，比较两组间各指标差异。采用Spearman检验GDM发生的独立危险因素与外周血细胞因子水平的相关性。结果 两组患者间的糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、空腹血糖(FPG)、餐后1 h血糖(OGTT-1h)、餐后2 h血糖(OGTT-2h)、胰岛素抵抗指数(HOMA-IR)相比，差异均具有统计学意义(P<0.05)。与对照组相比，GDM组外周血中NK细胞占比、CD3-CD56^dim     

ω-3多不饱和脂肪酸预处理对创伤性休克大鼠继发性肝损伤的影响

目的 评价ω-3多不饱和脂肪酸(ω-3 PUFA)预处理对创伤性休克大鼠继发性肝损伤的影响.方法 雄性Wistar大鼠48只,3月龄,体重240～260 g,采用随机数字表法,将其随机分为4组(n=12):假手术组(S组)、S+ω-3 PUFA组、创伤性休克组(TS组)和TS+ ω-3 PUFA组.TS+ ω-3 PUFA组与S+ ω-3PUFA组分别于造模前12 h、造模前2h时经尾静脉注射ω-3 PUFA 2 ml/kg,S组和TS组注射等容量生理盐水.建立大鼠股骨骨折合并失血致创伤性休克模型,模型制备成功后2h采集颈动脉血,检测血清ALT、AST活性及8-异前列腺素F2α(8-iso-PGF2α)、TNF-α浓度,随后处死大鼠取肝组织,检测肝组织SOD活性及MDA、谷胱甘肽(GSH)含量,光镜下观察肝组织病理学结果,并进行肝损伤评分.结果 与S组比较,TS组和TS+ω-3 PUFA组血清ALT、AST活性及8-iso-PGF2α、TNF-α浓度升高,肝组织MDA含量升高,SOD活性及GSH含量降低,肝组织损伤评分升高(P＜0.01);与TS组比较,TS+ ω-3 PUFA组血清ALT、AST活性及8-iso-PGF2α、TNF-α浓度降低,肝组织MDA含量降低,SOD活性及GSH含量升高,肝组织损伤评分降低(P＜0.05或0.01).结论 ω-3 PUFA预处理可减轻创伤性休克大鼠继发性肝损伤,与其抑制脂质过氧化反应和炎性反应有关.     

Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM

The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. The membrane protein plasma cell membrane glycoprotein-1 (PC-1) has been identified as an inhibitor of insulin receptor tyrosine kinase (IRTK) activity. We investigated insulin receptor function and PC-1 levels in muscle from three groups of obese subjects: women with GDM, pregnant women with normal glucose tolerance, and nonpregnant control subjects. Subjects (n = 6 for each group) were similar in age and degree of obesity (body fat >30%). IRTK activity, insulin receptor tyrosine phosphorylation, and protein levels of membrane glycoprotein PC-1 were determined in rectus abdominus muscle biopsies obtained at the time of either elective cesarean section or gynecological surgery. No significant differences were evident in basal insulin receptor tyrosine phosphorylation or IRTK activity in the three groups. After maximal insulin (10(-7) mol/l) stimulation, IRTK activity measured with the artificial substrate poly(Glu,Tyr) increased in all subjects but was lower in women with GDM by 25% (P < 0.05) and 39% (P < 0.001) compared with pregnant and nonpregnant control subjects, respectively. Similarly, insulin receptor tyrosine phosphorylation was significantly decreased in subjects with GDM (P < 0.05) compared with pregnant and nonpregnant control subjects. Treatment of the insulin receptors with alkaline phosphatase to dephosphorylate serine/threonine residues increased insulin-stimulated IRTK activity significantly in pregnant control and GDM subjects (P < 0.05), but these rates were still lower compared with nonpregnant control subjects (P < 0.05). PC-1 content in muscle from GDM subjects was increased by 63% compared with pregnant control subjects (P < 0.05) and by 206% compared with nonpregnant control subjects (P < 0.001). PC-1 content was negatively correlated with insulin receptor phosphorylation (r = -0.55, P < 0.05) and IRTK activity (r = -0.66, P < 0.05). These results indicate that pregnant control and GDM subjects had increased PC-1 content and suggest excessive phosphorylation of serine/threonine residues in muscle insulin receptors and that both may contribute to decreased IRTK activity. These changes worsen in women with GDM when controlling for obesity. These postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life.     

妊娠期糖尿病患者骨密度检测及影响因素分析

目的 探讨妊娠期糖尿病患者骨密度情况及影响因素。方法 选择2007年12月至2012年5月在孝感市中心医院产检和住院的孕妇，其中，正常孕妇160例为对照组，临床确诊为GDM的患者156例，应用超声骨密度测定仪测定孕妇右侧跟骨骨密度，检测空腹血糖（FPG）、糖化血红蛋白(HbA1C)，并进行统计学分析。结果 妊娠期糖尿病组孕妇骨密度检测结果中BUA、SOS、SI均明显低于对照组(P<0.05)；妊娠期糖尿病组骨量减少、骨质疏松比例分别为15.38%、5.13%，明显高于对照组(P<0.05)；Pearson相关分析显示SI与年龄、孕周、FBS、HbA1C呈负相关（r=-0.160、-0.265、-0.160和-0.156，P<0.05），与BMI呈正相关（r=0.069，P<0.05）。结论 妊娠期糖尿病患者骨量减少及骨质疏松发生率较正常孕妇明显升高；且跟骨超声骨密度SI与年龄、孕周、FBS、HbA1C呈负相关，与BMI呈正相关。     

血液透析红细胞生成素抵抗患者pro-hepcidin与炎性反应和铁代谢的关系

目的 研究维持性血液透析(MHD)红细胞生成素(EPO)抵抗患者pro-hepcidin与炎性反应和铁代谢的关系.方法 40例MHD患者为研究对象,其中20例EPO低反应和20例EPO正常反应.20例健康体检者为对照组.检测参试者的血红细胞计数(RBC)、血红蛋白(Hb)、网织红细胞计数(Ret)、红细胞比容(Hct)、血清铁蛋白(SF)、转铁蛋白(TF)、血清铁和总铁结合力、转铁蛋白饱和度(TSAT)(TSAT=血清铁/总铁结合力)、血清pro-hepcidin、血清超敏C反应蛋白(hs-CRP),并比较组间差异.Pearson相关法分析pro-hepcidin的影响因素.ROC曲线预测pro-hepcidin对EPO抵抗的价值.结果 MHD患者SF、血清pro-hepcidin、hs-CRP显著高于健康对照者(P＜0.01),TF显著低于健康对照者(P＜0.05).EPO抵抗患者血清铁蛋白、血清pro-hepcidin、hs-CRP明显高于反应正常的患者(P＜0.01).Pearson相关分析显示MHD EPO抵抗患者血清pro-hepcidin水平与血清铁蛋白(r=0.843,P=0.000)和hs-CRP(r=0.695,P=0.001)呈正相关.预测EPO抵抗的ROC曲线显示,pro-hepcidin、SF、hs-CRP曲线下面积分别为0.713、0.769和0.958.结论 EPO抵抗与炎性反应和铁代谢相关.血清pro-hepcidin、SF、hs-CRP有可能成为EPO抵抗的标志.     

Assessment of iron status by erythrocyte ferritin in uremic patients with or without recombinant human erythropoietin therapy.

Erythrocyte ferritin may be a better estimator of iron bioavailability than the conventional markers of iron stores (serum ferritin and transferrin saturation). To investigate the accuracy of these conventional markers in uremic patients compared with erythrocyte ferritin, we studied 29 chronic hemodialysis patients on erythropoietin (EPO) therapy, 18 without EPO therapy, and 22 healthy control subjects. Apart from the red blood cell indices, serum ferritin, transferrin saturation, and erythrocyte ferritin, the analytical study included red blood cell protoporphyrin and plasma aluminum levels. The control group showed erythrocyte ferritin concentrations between 8.3 and 12.5 attograms/cell (95% confidence interval). In the EPO group, red blood cell protoporphyrin correlated negatively with erythrocyte ferritin, but not with serum ferritin or transferrin saturation. In the non-EPO group, serum ferritin, erythrocyte ferritin, and transferrin saturation did not correlate with red blood cell protoporphyrin. Even though erythrocyte ferritin correlated well with serum ferritin in the EPO group (r = 0.61, P = 0.0003), the sensitivity of normal serum ferritin levels (30 to 300 ng/mL) to discard a low erythrocyte ferritin concentration (erythrocyte ferritin less than 7 ag/cell) was 0.53, while the sensitivity of serum ferritin at levels less than 30 ng/mL to indicate an absolute iron deficiency expressed as a low erythrocyte ferritin concentration was 0.28. Only values of serum ferritin and transferrin saturation greater than 300 ng/mL and 35%, respectively, could rule out a relative iron deficiency expressed as a low erythrocyte ferritin and high red blood cell protoporphyrin concentration. Plasma aluminum levels did not correlate with red blood cell protoporphyrin or erythrocyte ferritin levels in either uremic group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of circulating soluble transferrin receptor level in chronic haemodialysis patients.

BACKGROUND: The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTfR) concentrations in haemodialysis (HD) patients on maintenance recombinant human erythropoietin (rHuEpo) treatment. METHODS: In a prospective cross-sectional study, 91 chronic HD patients and 18 anaemic controls with normal renal function were recruited. For each subject, blood samples were measured for complete blood count, reticulocyte count, percentage of hypochromic red cells (% HRC), serum ferritin, serum iron, transferrin saturation (TS), serum erythropoietin (sEpo), C-reactive protein (CRP), and sTfR. HD patients received constant rHuEpo doses and basal sEpo was measured > or = 86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log(10)sTfR) as a dependent variable in the forward stepwise multiple regression model. RESULTS: HD patients were similar to controls regarding haematocrit, serum ferritin, TS, and % HRC, but had significantly lower sTfR, sEpo, and reticulocyte index. Univariate analyses showed that the sTfR level strongly correlated with sEpo (r=0.60, P<0.001) and % HRC (r=0.60, P<0.001), and significantly with serum ferritin (r=-0.29, P<0.01), TS (r=-0.27, P<0.05), and dose of rHuEpo administered (r=0.27, P<0.05) in HD patients. sTfR also had a positive correlation with haematocrit (r=0.26, P<0.05), red blood cell (RBC) count (r=0.23, P<0.05), and reticulocyte count (r=0.24, P<0.05), but not with CRP (r=0.16, P>0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTfR level. Overall, the model explained 58.8% of the variability in sTfR (R(2)=0.588, P<0.001). CONCLUSIONS: Circulating sTfR is a good index of marrow erythropoietic activity in HD patients during rHuEpo treatment. Its level is also independently up-regulated by functional iron deficiency in the process of enhanced erythropoiesis. Our study showed that sTfR levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.     

Effect of body iron stores on serum aluminum level in hemodialysis patients.

To evaluate the influence of body iron stores on the serum aluminum (Al) level, we studied the correlation between iron status (the serum ferritin, serum iron and transferrin saturation) and serum Al levels in 68 severely anemic hemodialysis patients. Among them, 36 underwent the desferrioxamine (DFO) mobilization test. These 68 patients were divided into three groups according to their serum ferritin level. The basal Al level in the patient group was 41.4 +/- 37.4 micrograms/l (control, 4.1 +/- 2.4 micrograms/l). The serum Al level after DFO infusion of the patient group was 111.1 +/- 86.8 micrograms/l. A significantly higher basal Al and peak Al level after DFO infusion were found in group 1 patients (serum ferritin less than 300 micrograms/l) when compared to group 2 (serum ferritin 300-1,000 micrograms/l) and group 3 (serum ferritin greater than 1,000 micrograms/l) patients. A significant negative correlation between serum ferritin and basal serum Al (r = -0.544, p = 0.0001), as well as peak serum Al after DFO infusion (r = -0.556, p = 0.0001), was noted. Similarly, a negative relationship between serum Al (both basal and peak) and either serum iron or transferrin saturation was noted. However, there was no correlation between the serum Al level and the dosage of aluminum hydroxide. In conclusion, serum ferritin, serum iron and transferrin saturation were inversely correlated with serum Al in our hemodialysis patients. Iron deficiency may probably increase Al accumulation in these patients.     

Impaired glucose transport and insulin receptor tyrosine phosphorylation in skeletal muscle from obese women with gestational diabetes.

Women who develop gestational diabetes mellitus (GDM) have severe insulin resistance and markedly increased risk to develop subsequent type 2 diabetes. We investigated the effects of pregnancy and GDM on glucose transport activity and the expression and phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1 in human skeletal muscle fiber strips in vitro. Rectus abdominis muscle biopsies were obtained at the time of cesarean section from 11 pregnant women with normal glucose tolerance (pregnant control), 7 pregnant women with GDM, and 11 nonpregnant women undergoing elective surgery (nonpregnant control). Subjects were matched for age and similar degree of obesity. The rate of maximal insulin (10(-7) mol/l)-stimulated 2-deoxyglucose transport was reduced by 32% (P < 0.05) in muscle strips from the pregnant control group and even further in GDM subjects by 54% (P < 0.05 vs. pregnant control). The maximal effect of insulin on tyrosine phosphorylation of the insulin receptor was 37% lower (P < 0.05) in GDM subjects than in pregnant control subjects and was not related to changes in the abundance of the insulin receptor. Compared with nonpregnant control subjects, maximal insulin-stimulated IRS-1 tyrosine phosphorylation was significantly lower by 59 +/- 24% (mean +/- SD) (P < 0.05) and 62 +/- 28% (P < 0.05) in pregnant control and GDM subjects, respectively. This was reflected by a 23% (P < 0.05) and 44% (P < 0.002) reduction in IRS-1 protein levels in muscle from pregnant control and GDM subjects. Both pregnant control and GDM subjects exhibited a 1.5- to 2-fold increase in the levels of IRS-2 (P < 0.01) and p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase (P < 0.05), despite reduced glucose transport activity. These data indicate that insulin resistance to glucose transport during pregnancy is uniquely associated with a decrease in IRS-1 tyrosine phosphorylation, primarily due to decreased expression of IRS-1 protein. However, in GDM subjects, a decrease in tyrosine phosphorylation of the insulin receptor beta-subunit is associated with further decreases in glucose transport activity. Thus, impaired insulin receptor autophosphorylation is an important early distinction underlying muscle insulin resistance in young women with GDM, and it may underlie future risk for the development of type 2 diabetes.     

Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes

Detailed metabolic studies were carried out to compare major regulatory steps in glucose metabolism in vivo between 25 normal pregnant Latino women without and 150 pregnant Latino women with gestational diabetes mellitus (GDM). The two groups were frequency-matched for age, BMI, and gestational age at testing in the third trimester. After an overnight fast, women with GDM had higher fasting plasma glucose (P = 0.0001) and immunoreactive insulin (P = 0.0003) concentrations and higher glucose production rates (P = 0.01) but lower glucose clearance rates (P = 0.001) compared with normal pregnant women. During steady-state hyperinsulinemia (approximately 600 pmol/l) and euglycemia (approximately 4.9 mmol/l), women with GDM had lower glucose clearance rates (P = 0.0001) but higher glucose production rates (P = 0.0001) and plasma free fatty acid (FFA) concentrations (P = 0.0002) than the normal women. These intergroup differences persisted when a subgroup of 116 women with GDM who were not diabetic < or = 6 months after pregnancy were used in the analysis. When all subjects were considered, there was a very close correlation between glucose production rates and plasma FFA concentrations throughout the glucose clamps in control (r = 0.996) and GDM (r = 0.995) groups. Slopes and intercepts of the relationships were nearly identical, suggesting that blunted suppression of FFA concentrations contributed to blunted suppression of glucose production in the GDM group. In addition to these defects in insulin action, women with GDM had a 67% impairment of pancreatic beta-cell compensation for insulin resistance compared with normal pregnant women. These results demonstrate that women with GDM have multiple defects in insulin action together with impaired compensation for insulin resistance. Our findings suggest that defects in the regulation of glucose clearance, glucose production, and plasma FFA concentrations, together with defects in pancreatic beta-cell function, precede the development of type 2 diabetes in these high-risk women.     

维持性血透患者血清NGAL水平与体内铁存储的相关性研究

目的:探讨在维持性血液透析患者,其血清NGAL(中性粒细胞明胶酶相关载脂蛋白)水平与体内铁存储的关系。方法:从2010年10月开始,我们纳入我院血液透析患者人数150例,同时纳入50例健康人为对照。收集患者及健康对照人群的人口学资料、相关的临床和生化学资料,透析前后NGAL及透析前CRP、转铁蛋白饱和度、铁蛋白、血清铁、转铁蛋白等。做透析前血清NGAL与CRP、转铁蛋白饱和度、铁蛋白、血清铁、转铁蛋白相关性分析。评估NGAL水平在判断体内铁存储的价值。结果:(1)血液透析患者其血清NGAL透析前水平为(445.45±50.34)ng/ml,透析后为(369±50.34)ng/ml,差异有统计学意义(P<0.05)。(2)血液透析患者其血清NGAL水平与CRP、spKt/V、TSAT等指标均有正相关关系(P<0.05),但与铁蛋白、血清铁、转铁蛋白无明显线性关系(P>0.05)。在多元线性回归模型中,NGAL水平与CRP、spKt/V、TSAT有相关关系(P<0.05)。(3)ROC曲线表明,NGAL水平较铁蛋白更好的反映体内铁存储情况,但差异无统计学意义(P>0.05)。结论:在血液透析患者,血清NGAL与spKt/V、CRP、TSAT有不同程度的正相关。血清NGAL能较好的反映体内铁存储情况。     

A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.