肥胖及2型糖尿病患者血清apelin水平及其相关因素分析

目的测定肥胖及新诊断2型糖尿病患者血清apelin水平，探讨apelin与体脂、糖、脂代谢、胰岛素抵抗等的相关性。方法62例2型糖尿病患者和72例正常糖调节（NGR）者按体重指数（BMI）≥25kg／m^2或〈25kg／m^2又各自分为超重／肥胖与正常体重亚组，采用放射免疫分析法检测空腹血清apelin水平，同时检测空腹血糖（FPG）、HbA1C、血脂各项指标及空腹胰岛素（FINS）水平，计算BMI和腰臀比，并以稳态模型计算胰岛素抵抗指数（HOMA-IR）。结果校正年龄及性别后，2型糖尿病组血清apelin水平高于NGR组[（317．9±99．6vs279．0±66．8）ng／L，P〈0．01]，2型糖尿病组和NGR组中的超重／肥胖者均高于非肥胖者[（354．0±114．4vs274．1±53．0）ng／L，（299．2±74．5vs252．8±48．9）ng／L，均P〈0．05]，且2型糖尿病超重／肥胖组明显高于NGR肥胖组（P〈0．01）；偏相关分析显示，空腹血清apelin与BMI、ln（HOMA-IR）、FPG、总胆固醇（TC）呈正相关（r=0．353，r=0．355，r=0．224，r=0．241，均P〈0．01），与腰围、收缩压呈正相关（r=0．263，r=0．183，P〈0．05）。多元逐步回归分析发现，BMI、ln（HOMA—IR）和TC是血清apelin的独立相关因素。结论血清apelin水平在肥胖和初发的2型糖尿病人群中升高，且与BMI、HOMA-IR及脂代谢相关，推测apelin可能参与构成胰岛素抵抗综合征的病理生理基础。     

高原慢性阻塞性肺疾病合并慢性肺心病低氧血症与肿瘤坏死因子系统活性及对营养不良的影响

目的探讨高原地区慢性阻塞性肺疾病（COPD）合并慢性肺心病（CCP）患者低氧血症与肿瘤坏死因子-α（TNF-α）系统活性的关系,及对营养不良的影响。方法对高原地区（海拔2260—3500m）52例COPD合并CCP低氧血症缓解期患者测定了血清TNF-α和血浆可溶性肿瘤坏死因子受体-55（sTNF—R55）、1s用力呼气容积占预计值百分比（FEV1％）、动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaCO2）、体重（BW）、理想体重百分比（％NW）和体重指数（BMI）,并与30名年龄相似的平原健康人作对照。结果COPD合并CCP组BW、％NW、BMI、FEV,％和PaO：显著低于对照组,PaCO2、血清TNF—d和血浆sTNF-1／55显著高于对照组（均P〈0．01）。COPD合并CCP组PaO,水平与血清TNF—OL、血浆sTNF—R55水平呈显著负相关（TNF-α：r=-0．787,P〈0．01;sTNF—R55;r=-0．802,P〈0．01）,TNF—α、sTNF—R55与BMI呈显著负相关（TNF一仪：r=-0．785,P〈0．01;sTNF-R55：r=-0．791,P〈0．01）,TNF—α与sTNF—R55水平呈显著正相关（sTNF-R55;r=0．702,P〈0．01）。COPD合并CCP患者中,PaO2〈45mmHg亚组TNF-α、sTNF—R55水平显著高于Pa02≥45mmHg亚组（均P〈0．01）;BMI〈18．0kg／m^2亚组的TNF—α、sTNF—R55水平显著高于≥18．0kg／m^2亚组（均P〈0．01）;BMI〈18．0kg／m^2患者PaO2〈45mmHg亚组的TNF—α、sTNF—R55水平显著高于Pa02I〉45mmHg亚组（均P〈0．05）。结论高原COPD合并慢性肺心病全身低氧血症患者体内肿瘤坏死因子．理系统活性增强,这可能是导致本病患者发生营养不良的重要因素。     

氯沙坦和氨氯地平对肥胖高血压患者瘦素、脂联素及胰岛素敏感性的影响

目的观察血管紧张素Ⅱ受体拮抗剂氯沙坦和钙离子通道拮抗剂氨氯地平对肥胖高血压患者血浆瘦素、脂联素、去甲肾上腺素（NE）水平和胰岛素敏感性的影响。方法采用放射免疫法测定血浆瘦素及脂联素水平、采用稳态模型评价胰岛素抵抗指数（HOMA-IR），以高效液相色谱检测血浆NE水平。结果氯沙坦组血浆瘦素、脂联素、HOMA—IR、体重指数（BMI）治疗16周前后差异有统计学意义[分别为（35．6±18．5vs32．0±17．1）μg／L，P〈0．05；（9．34±3．12vs12．45±4．52）mg／L，P〈0．01；8．6±2．7vs6．1±2．1，P〈0．05；（28．9±3．8vs27．3±3．2）kg／m^2，P〈0．05]，氨氯地平组在治疗前后差异均无统计学意义[分别为（35．2±18．3vs35．4±18．9）μg/L；（9．32±3．23vs9．39±3．41）mg／L；8．3±2．5vs8．7±2．9；（28．8±3．8vs28．7±3．6）kg／m^2]；血浆NE水平在氨氯地平组治疗后明显增加[（324±112vs449±122）ng／L，P〈0．01]，氯沙坦组治疗前后差异无统计学意义[（322±115vs325±121）ng／L]，两治疗组之间的疗效差异有统计学意义（P〈0．01）。结论虽然氯沙坦和氨氯地平有等同的降压效应，但氯沙坦尚能改善与肥胖相关的代谢紊乱，因此肥胖高血压患者用氯沙坦比氨氯地平治疗可能会获得更多益处。     

稳定期慢性阻塞性肺疾病患者深吸气量测定的临床意义

目的探讨深吸气量测定对稳定期慢性阻塞性肺疾病（COPD）患者气流阻塞变化和呼吸困难严重程度的临床意义。方法对61例中度稳定期COPD患者进行常规肺功能检测，以Borg指数判断受试者呼吸困难的严重程度。所有患者在吸入400μg沙丁胺醇后重复检测肺功能和呼吸困难分级，36例在进行6min步行试验（6MWT）后重复肺功能检测和呼吸困难分级。结果吸入沙丁胺醇后，COPD患者的深吸气量和第一秒用力呼气容积（FEV1）分别为（1．6±0．5）和（1．3±0．4）L，均显著高于吸入前的（1．4±0．5）和（1．1±0．4）L，深吸气量平均改善率为（20±16）％，FEV。平均改善率为（11±4）％，差异有统计学意义（t=-3．970，P〈0．01）；其中深吸气量改善率≥10％的占75．4％（46／61），FEV1改善率≥10％的占39．3％（24／61），差异有统计学意义（x^2=16．190，P〈0．01）。治疗后Borg指数（3．0±0．7）显著低于治疗前（3．9±0．8）。6MWT后，COPD患者深吸气量为（1．1±0．4）L，FEV1为（1．0±0．4）L，均显著低于6MWT前的（1．4±0．5）和（1．1±0．4）L，深吸气量平均恶化率为（26±8）％，FEV1平均恶化率为（14±6）％，差异有统计学意义（t=-7．279，P〈0．01），其中深吸气量恶化率≥10％的占100％（36／36），FEV1恶化率≥10％的占72．2％（26／36），差异有统计学意义（x^2=11．613，P〈0．01）。运动后Borg指数（5．6±1．0）显著高于运动前（3．9±0．9）。治疗前后深吸气量差值与治疗前后Borg指数差值、运动前后深吸气量差值与运动前后Borg指数差值均呈显著正相关。静息状态未吸入沙丁胺醇时深吸气量与功能残气量、治疗前后深吸气量差值与治疗前后功能残气量差值、运动前后深吸气量差值与运动前后功能残气量差值均呈显著负相关。结论与FEV1比较，深吸气量检出稳定期COPD患者气流阻塞变化的敏感性比较高，能较准确地反映患者呼吸困难的严重程度。     

慢性阻塞性肺疾病的肺功能分级与体质量指数的关系研究

目的讨论COPD的肺功能的各个分级与体质量指数（BMI）之间的相关性。方法选取我院呼吸内科二病房2010年7月-2012年7月确诊为COPD急性加重期患者197例,根据其肺功能的严重程度分级,分别与肺功能正常组进行比较,分析讨论肺功能分级与BMI之间的相关性。结果COPD组、正常组的BMI分别是（21．51±3．90）kg／m^2、（23．02±3．20）kg／m^2。两组之间相比较,差异有统计学意义（P〈0．05）。COPD按严重程度与年龄分组后比较各组BMI,差异有统计学意义（P〈0．05）。结论COPD及其严重程度和年龄与BMI存在相关性。     

老年高血压病患者血浆神经肽Y、神经降压素水平变化与心肾功能损害的相关分析

目的观察老年高血压病患者血浆神经肽Y（NPY）、神经降压素（NT）水平变化与心肾功能损害的关系。方法选择符合高血压病诊断标准的解放军总医院第一附属医院住院的老年患者57（男性36，女性21）例，年龄60～88（71．3±6．8）岁，选择23（男16，女7）例老年健康查体者或健康志愿者作为对照组，年龄60～76（65．5±6．6）岁。用彩色超声心动图检查患者心脏结构和功能。测定内生肌酐清除率（Ccr）评价患者肾功能。用放射免疫分析法检测血浆NPY、NT浓度。结果（1）老年高血压病患者血浆NPY水平（159±56）pg／ml高于老年对照组（123±54）pg／ml（t=-2．585，P〈0．05），而NT水平（66±31）pg／ml明显低于对照组（101±19）pg／ml（t=2．617，P〈0．01）。（2）将老年高血压病患者按左室射血分数（LVEF）分为3组（1组：LVEF≥55％，2组：LVEF=41％～54％，3组：LVEF≤40％）。3组间NPY、NT浓度均差异明显（F=12．36，P〈0．01，F=4．92，P〈0．05），随心功能恶化，NPY水平升高，而NT水平降低。伴有左室肥厚[室间隔≥11mm和（或）左室后壁≥11mm为左室肥厚]组血浆NPY水平（177±52）pg／ml高于室间隔和左室后壁正常组（135±47）pg／ml（t=-2．84，P〈0．01），而NT水平则肥厚组（56±25）pg／ml低于正常组（94±31）pg／ml（t=4．74，P〈0．01）。（3）将患者按其肾功能，Ccr≥50ml／min和Ccr≤49ml／min分为两组，Ccr≤49ml／min组血浆NPY水平（187±53）pg／ml高于Ccr≥50ml／min组（148±55）pg／ml（t=-1．978，P〈0．05）。NT水平二组分别为（61±29）pg／ml和（69±33）pg／ml，比较未显示出明显差异（t=0．991，P〉0．05）。结论老年高血压病患者血浆NPY、NT水平变化与患者心肾功能损害程度相关，观察血浆NPY、NT水平变化有助于判断老年高血压病患者的病情和预后。     

支气管哮喘和慢性阻塞性肺疾病患者诱导痰中基质金属蛋白酶及其抑制剂与气道炎症及气流受限

目的探讨支气管哮喘（简称哮喘）和慢性阻塞性肺疾病（COPD）患者诱导痰中基质金属蛋白酶9（MMP-9）和基质金属蛋白酶抑制剂1（TIMP-1）的水平及其与炎性细胞数、肺功能的关系。方法分别选择14例缓解期哮喘患者（哮喘组）、12例稳定期COPD患者（COPD组）和10名健康对照者（健康对照组）进行肺功能测定和用诱导痰检查方法对痰炎性细胞进行分类计数，并用酶联免疫吸附试验（ELISA）法测定诱导痰上清液中自细胞介素4（IL-4）、MMP-9和TIMP-1浓度。结果哮喘组患者诱导痰中嗜酸粒细胞、中性粒细胞分别为0．181±0．067、0．30±0．07，健康对照组为0．007±0．005、0．26±0．06，COPD组为0．042±0．017、0．50±0．10，3组细胞间比较差异有统计学意义（F值分别为4．32、4．13，P均〈0．05）。哮喘组、COPD组、健康对照组间诱导痰中IL-4浓度分别为（19±7）×10^-3／L、（14±6）×10^-3g／L、（11±4）×10^-3g／L，3组诱导痰中IL-4浓度比较差异无统计学意义（F=1．56，P均〉0．05），且分别与嗜酸粒细胞、中性粒细胞和第一秒用力呼气容积占预计值百分比（FEV1占预计值％）无相关（r分别为0．33、0．11、0．19、0．25、0．39、0．40、0．21、0．35、0．17，P均〉0．05）。哮喘组和COPD组诱导痰中MMP-9、TIMP-1浓度分别为（15．9±6．0）g／L、（13．4±5．1）g／L、（19．8±8．5）g／L、（16．7±7．6）g／L，健康对照组分别为（1．8±1．1）g／L、（1．3±0．9）g／L，两组MMP-9、TIMP-1浓度比较差异有统计学意义（F值分别为2．99、4．22，P均〈0．05）。哮喘组MMP-9浓度与嗜酸粒细胞呈正相关（r=0．71，P〈0．05）；COPD组MMP-9浓度与中性粒细胞呈正相关（r=0．59，P〈0．05），但与FEV。占预计值％和第一秒用力呼气容秽用力肺活量（FEV1／FVC）无相关（r分别为0．22、0．16、0．25、0．30，P均〉0．05）。哮喘组和COPD组TIMP．1浓度均与嗜酸粒细胞和中性粒细胞无相关（r分别为0．27、0．31、0．20、0．35，P均〉0．05），但与FEV。占预计值％呈负相关（r分别为-0．58、-0．62，P均〈0．05）。哮喘组和COPD组诱导痰中MMP-9／TIMP-1比值分别为0．8±0．7、0．8±0．6，两组比较差异无统计学意义（F=1．78，P〉0．05），但与健康对照组（1．5±0．6）比较差异有统计学意义（F=3．70，P〈0．05），且与FEV1占预计值％呈正相关（r分别为0．56、0．61，P均〈0．05）。结论哮喘组和COPD组患者诱导痰中MMP-9／TIMP-1比值的失衡与气道炎症和气流受限有关，这种失衡在哮喘和COPD细胞外基质的重塑和气流受限的发病机制中发挥重要作用。     

不同病理类型的2型糖尿病肾病患者临床特征比较

目的回顾性分析并比较不同病理类型的2型糖尿病肾病患者的临床特征。方法1990年12月至2004年4月在我院肾脏病研究所住院并行肾穿刺活检的150例2型糖尿病肾病患者，其中弥漫性系膜硬化病变（DIF）患者73例，结节性肾小球硬化病变（NOD）患者77例。分析并比较以下指标：糖尿病病程，高血压病程，体重指数（BMI），眼底病变，HbA1C血浆白蛋白，血脂水平，24h尿蛋白定量，N-乙酰-β-氨基葡萄糖苷酶（NAG），尿渗透压，肌酐清除率。结果（1）NOD组患者糖尿病病程较DIF组患者长[（122．0±8．1 vs 56．0±7．8）个月，P〈0．01]，高血压病程较DIF组患者短[（49．0±10．3 vs 84．0±12．6）个月，P〈0．05]，BMI较DIF组患者低[（24．1±0．4 vs 26．1±0．4）kg／m^2，P〈0．01]，尿蛋白水平较DIF组高[（3．8±0．3 vs 1．9±0．2）g／24h，P〈0．01]，肌酐清除率较DIF组患者低（45．2±3．1 vs 64．4±3．6）ml／min；（2）NOD组患者中，92％有糖尿病视网膜病变，显著高于DIF组的13％（P〈0．01）。结论不同病理类型的糖尿病肾病患者临床特征不同，NOD组患者的糖尿病病程更长，肾脏损害更明显，更容易出现糖尿病视网膜病变；DIF患者高血压病程更长，BMI更高。     

冠心病与血管紧张素转换酶和内皮型一氧化氮合酶基因多态性及交互作用的临床研究

目的联合对冠心病患者血管紧张素转换酶（ACE）基因多态性和内皮型一氧化氮合酶（eNOS）基因G894T多态性进行分析,探讨基因多态性与冠心病的关系和交互作用及遗传学机制在冠心病发病及预后中的临床意义。方法应用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）分析技术检测236例冠心病患者及190例正常人ACE和eNOS两种基因多态性。同时测定血脂、血糖、体重指数（BMI）、左室射血分数（LVEF）和血压。结果冠心病组ACE基因DD型频率[36％（86／236）]显著高于对照组[19％（36／190）,P〈0．01],Ⅱ型频率[27％（64／236）]显著低于对照组[49％（93／190）,P〈0．05]。冠心病组DD型甘油三酯（TG）[（2．2±1．7）mmol／L]显著高于Ⅱ型TG[（1．6±0．8）mmol／L和ID型TG[（1．7±0．9）mmol／L,均P〈0．05],DD型高密度脂蛋白胆固醇[HDL—C（1．2±0．4）mmol／L]显著低于Ⅱ型HDL—C[（1．3±0．3）mmol／L,P〈0．05],DD型血糖[（6．2±1．7）mmol／L]和BMI[（25．7±2．8）kg／m^2]显著高于ID型[血糖：（5．6±1．3）mmol／L,BMI：（24．8±3．1）kg／m^2。,P〈0．05],DD型LVEF（56％±14％）显著低于Ⅱ型LVEF（62％±15％）和ID型LVEF（61％±14％）,均P〈0．05。收缩压、舒张压、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）、糖尿病组与非糖尿病组、急性冠状动脉综合征组与非急性冠状动脉综合征组、单支病变组与多支病变组在ACE和eNOS基因不同基因型之间差异均无统计学意义。冠心病组eNOS基因GT型频率[28％（67／236）]显著高于对照组[17％（32／190）,P〈0．01],GG型频率与对照组比较,差异无统计学意义。TG、HDL—C、血糖、BMI和LVEF在eNOS基因不同基因型之间差异均无统计学意义（均P〉0．05）。携带DD型患冠心病的概率是携带Ⅱ型的1．74倍（P〈0．01）,携带GT型患冠心病的概率是携带GG型的1．73倍（P〈0．05）。两种基因对患冠心病的交互作用显示为如同时携带Ⅱ型和GG型,患冠心病的概率是37．9％,而同时携带DD型和GT型患冠心病的概率是77．8％。结论ACE基因多态性和eNOS基因多态性与冠心病及某些危险因素显著相关,同时携带DD型和GT型两种易患基因型时,患冠心病的概率明显增加,具有显著的遗传倾向。     

原发性醛固酮增多症患者与左心室肥厚

目的探讨原发性醛固酮增多症（原醛）及其主要亚型：腺瘤型和增生型的左室肥厚情况。方法入选确诊原醛患者250例。其中142例行分侧肾上腺静脉取血，分为原醛腺瘤组68例，原醛增生组74例，选取同期年龄、性别、24小时平均血压相匹配的原发性高血压（EH）患者246例作为对照，所有入选者记录一般临床资料和生化指标，并行超声心动图检查。结果1）左室舒张末期内径原醛组[（49．6±4．3）mm]高于EH组[（48．3±4．2）mm，P〈0．053，原醛组左室后壁厚度[原醛组（10．5±2．2）mm vs EH组（9．9±1．1）mm]、左室质量（LVM）[原醛组（232．2±75．1）g vs EH组（207．5±46．6）g]、左室质量指数（LVMI）[原醛组（131．9±37．4）g／m^2 vs EH组（118．3±23．7）g／m^2]显著高于EH组（P均〈0．01）。2）在原醛组中LVMI与收缩压及立位血浆醛固酮独立相关。3）1级高血压中原醛组的LVMI高于EH组，但差异无统计学意义（P〉0．05）；2级、3级高血压中，原醛组的LVMI高于EH组（P〈0．05或P〈0．01）。4）左室后壁厚度[原醛组（10．8±3．0）gVSEH组（10．3±1．3）g，P〈0．053；、LVM[原醛组（249．5±81．7）g vs EH组（219．4±67．7）g，P〈0．01]、LVMI[原醛组（139．9±41．0）g／m^2 vs EH组（125．1±32．9），P〈0．01]原醛腺瘤组显著高于原醛增生组。5）左室肥厚在EH组、原醛腺瘤组和增生组的构成比分别为42．7％，63．2％和43．2％，3组之间差异有统计学意义（P=0．009）。结论原醛患者左室肥厚的发病率高于EH患者，其中以原醛腺瘤组更为严重。     

Circulating levels of soluble Fas ligand in cachexic patients with COPD are higher than those in non-cachexic patients with COPD

OBJECTIVE: Apoptosis may be involved in the pathophysiology of cachexia in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the potential role of the Fas-Fas ligand (FasL) system in cachexic patients with COPD. PATIENTS AND METHODS: We measured the circulating levels of soluble FasL (sFasL), with a newly developed, highly sensitive enzyme-linked immunosorbent assay system in seventy patients with COPD and forty-seven control subjects. RESULTS: The levels of sFasL in the COPD patients were significantly lower than those in the control subjects (46+/-29 vs. 55+/-28 pg/ml; p<0.05), whereas the levels of soluble Fas (sFas) remained unchanged between the two groups. The significant correlation between the levels of sFasL and sFas, observed in the control subjects (r=0.304; p<0.05), was absent in the COPD patients. Cachexic COPD patients with a relatively lower BMI (BMI <20 kg/m(2), n=45) and %fat (%fat <20%, n=34), showed significantly increased levels of sFasL compared to non-cachexic COPD patients with a relatively higher BMI (BMI > or =20 kg/m(2), n=25) and %fat (%fat > or =20%, n=36) (BMI; 51+/-33 vs. 36+/-15 pg/ml; p<0.05. %fat; 55+/-33 vs. 37+/-21 pg/ml; p<0.01), due to the inverse relationships between the body composition measurements and the levels of sFasL observed exclusively in the patients (BMI; r=-0.307; p<0.05. %fat; r=-0.283; p<0.05). CONCLUSION: These results may suggest that the Fas-FasL system does not play a significant role in the potential triggers of enhanced apoptosis leading to skeletal muscle wasting and adipose tissue depletion in cachexic patients with COPD.     

Chronic obstructive pulmonary disease and body mass index in five Latin America cities: the PLATINO study

BACKGROUND: The body mass index (BMI) is a prognostic factor for chronic obstructive pulmonary disease (COPD). Despite its importance, little information is available regarding BMI alteration in COPD from a population-based study. We examined characteristics by BMI categories in the total and COPD populations in five Latin-American cities, and explored the factors influencing BMI in COPD. METHODS: COPD was defined as a postbronchodilator forced expiratory volume in the first second/forced vital capacity (FEV(1)/FVC) <0.70. BMI was categorized as underweight (< 20 kg/m(2)), normal weight (20-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (> or = 30.0 kg/m(2)). RESULTS: Interviews were completed in 5571 subjects from 6711 eligible individuals, and spirometry was performed in 5314 subjects. There were 759 subjects with COPD and 4555 without COPD. Compared with the non-COPD group, there was a higher proportion of COPD subjects in the underweight and normal weight categories, and a lower proportion in the obese category. Over one-half COPD subjects had BMI over 25 kg/m(2). No differences in BMI strata among countries were found in COPD subjects. Factors associated with lower BMI in males with COPD were aging, current smoking, and global initiative for chronic obstructive lung disease (GOLD) stages III-IV, whereas wheeze and residing in Santiago and Montevideo were associated with higher BMI. In females with COPD, current smoking, lower education, and GOLD stages II-IV were associated with lower BMI, while dyspnea and wheeze were associated with higher BMI. CONCLUSIONS: BMI alterations are common in COPD with no significant differences among countries. Current smoking, age, GOLD stages, education level, residing in Santiago and Montevideo, dyspnea and wheeze were independently associated with BMI in COPD.     

Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea

It is well known that obstructive sleep apnoea is especially frequent in the morbidly obese. In these subjects diurnal chronic hypercapnia, whose mechanism is still debated, may be present. Our study was performed to evaluate the prevalence and the mechanism of diurnal hypercapnia in the morbidly obese affected by obstructive sleep apnoea. From a population referred to our centre because of suspicion of sleep related breathing disorders, we selected 285 subjects without cardiopulmonary, neuromuscular or endocrinological diseases: 89 (36 M and 53 F, aged 46+/-13 years) had body mass index (BMI) > or = 40 kg m(-2) (MO group: morbidly obese subjects) and 196 (99 M and 97 F, aged 48+/-16 years) had BMI <40 kg m(-2) (NMO group: non-morbidly obese subjects). Then the MO group was divided into three subgroups: normocapnic subjects without obstructive sleep apnoea, normocapnic subjects with obstructive sleep apnoea, hypercapnic subjects with obstructive sleep apnoea; while we found no hypercapnic subject without obstructive sleep apnoea. All subjects underwent anthropometric evaluations and bioelectrical impedance analyses, respiratory function tests and arterial blood gas analysis, a modified version of the Sleep and Healthy questionnaire and a full night polysomnography. Our results showed that hypercapnia (PaCO2 > or = 45 mm Hg) associated with obstructive sleep apnoea [respiratory disturbance index (RDI) > or = 10 h(-1)] was found in 27% of the morbidly obese subjects, but only in 11% of the nonmorbidly obese ones (P<0.01). The comparison among the three subgroups, in which we divided the morbidly obese subjects, shows that those with hypercapnia and obstructive sleep apnoea had significantly more important ventilatory restrictive defects [forced vital capacity (FVC)% of pred 73.27+/-14 81 vs. 82.37+/-16.93 vs. 87.25+/-18.14 respectively; total lung capacity (TLC)% of pred 63.83+/-16.35 vs. 79.11+/-14.15 vs. 87.01+/-10.5], a significantly higher respiratory disturbance index (RDI 46.34+/-26.90 vs. 31.79+/-22.47 vs. 4.98+/-3.29) a longer total sleep time with oxyhaemoglobin saturation<90% [total sleeptime (TST)SaO2<90% 63.40+/-33.86 vs. 25.95+/-29.34 vs. 8.22+/-22.12] and a lower rapid eye movement (REM) stage (9.5+/-1.2 vs. 14.0+/-0.9 vs. 17.05+/-1.2) than normocapnic subjects with obstructive sleep apnoea or subjects without obstructive sleep apnoea. The best model to predict PaCO2 resulted from a combination of TSTSaO2<90% (r2 = 0.22, P<0.001), forced expiratory volume in 1 sec (FEV1)% of pred (r2 = 0.09, P<0.01), FVC % of pred (r2 = 0.075, P<0.01). In conclusion our study suggests that diurnal hypercapnia is frequently associated with obstructive sleep apnoea in the morbidly obese without chronic obstructive pulmonary disorder (COPD) and that ventilatory restriction and sleep related respiratory disturbances correlate to diurnal hypercapnia.     

慢性阻塞性肺疾病患者肺动脉高压时肺动脉平滑肌细胞的增殖与凋亡

目的探讨慢性阻塞性肺疾病（COPD）患者肺动脉高压及肺血管重塑的机制。方法将患者分为非COPD非肺动脉高压组（A组）、COPD非肺动脉高压组（B组）和COPD并肺动脉高压组（C组），应用免疫组织化学方法检测肺动脉平滑肌细胞增殖细胞核抗原（PCNA），用原位缺口末端DNA碎片标记技术检测肺动脉平滑肌细胞凋亡。结果A组肺小动脉管壁较薄，管腔较大；B组管壁厚度增加，管腔变窄，其程度介于A组和C组之间；C组肺小动脉管壁明显增厚，管腔明显变窄，平滑肌细胞增生肥大，呈现明显的肺血管重塑现象；图像分析结果表明。B组及C组管壁厚度占外径的百分比（WT％）和血管壁横断面积占血管总面积的百分比（WA％）分别为（20±4）和（35±5）％、（28±5）和（50±6）％，明显高于A组的（16±3）和（25±3）％。C组与B组相比，WT％及WA％明显增高。3组肺小动脉壁平滑肌细胞均存在一定比例的增殖与凋亡，B组和C组肺小动脉平滑肌细胞增殖指数（PI）为（19±5）和（38±7）％，明显高于A组的（8±2）％；两组凋亡指数为（4．5±1．3）和（3．1±1．3）％，均明显低于A组的（6．9±1．9）％；B组肺动脉平滑肌细胞增殖指数低于C组，而凋亡指数高于C组。C组及B组氧分压与肺动脉平滑肌细胞增殖指数成负相关（r=-0．519，P=0．003），与肺动脉平滑肌细胞凋亡指数成正相关（r=0．441，P=0．015）。结论肺动脉平滑肌细胞增殖增加和凋亡减少。由此引起增殖与凋亡失衡是COPD患者肺血管重塑及发生肺动脉高压的主要机制；缺氧是引起肺动脉平滑肌细胞增殖增加和凋亡减少的主要原因之一。     

Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients.

OBJECTIVE: Insulin inhibition of insulin secretion has been described in normal lean subjects. In this study, we examined whether this phenomenon also occurs in the morbidly obese who often have severe peripheral insulin resistance. SUBJECTS: Twelve obese patients, normotolerant to glucose (8 F/4 M, body mass index (BMI)=54.8+/-2.5 kg/m(2), 39 y) and 16 lean control subjects (10 F/6 M, BMI=22.0+/-0.5 kg/m(2), 31 y). DESIGN AND MEASUREMENTS: An experimental study using various parameters, including an euglycemic hyperinsulinemic clamp (280 pmol/min/m(2) of body surface), an oral glucose tolerance test (OGTT), electrical bioimpedance and indirect calorimetry. RESULTS: The obese subjects were insulin resistant (M=19.8+/-1.6 vs 48.7+/-2.6 micromol/min kg FFM, P<0.0001) and hyperinsulinemic in the fasted state and after glucose ingestion. Fasting plasma C-peptide levels (obese 1425+/-131 pmol/l vs lean 550+/-63 pmol/l; P<0.0001) decreased less during the clamp in the obese groups (-16.9+/-6.9% vs -43.0+/-5.6% relative to fasting values; P=0.007). In the lean group, the C-peptide decrease during the clamp (percentage variation) was related to insulin sensitivity, M/FFM (r=0.56, P=0.03), even after adjustment for the clamp glucose variation. CONCLUSION: We conclude that, in lean subjects, insulin inhibits its own secretion, and this may be related to insulin sensibility. This response is blunted in morbidly obese patients and may have a role in the pathogenesis of fasting hyperinsulinemia in these patients.     

脂多糖对慢性阻塞性肺疾病患者气道上皮细胞Toll样受体4表达的影响

目的探讨脂多糖(LPS)对慢性阻塞性肺疾病(COPD)患者原代培养的气道上皮细胞Toll样受体4(TLR4)介导的炎症反应及其作用机制。方法华中科技大学同济医学院同济医院胸外科2004年1月至10月因肺部肿瘤而行肺叶切除术的患者24例,体外分离其肺标本并培养气道上皮细胞,根据肺功能检查结果及有无吸烟史分为COPD组、非COPD吸烟对照组及非COPD不吸烟对照组,每组8例。用100μg／L LPS刺激原代培养的气道上皮细胞;采用流式细胞仪(FCM)检测原代培养的气道上皮细胞表面的TLR4,逆转录-聚合酶链反应(RT-PCR)检测其TLR4 mRNA表达。结果FCM检测显示,COPD组的气道上皮细胞表面TLR4荧光阳性细胞数[(10．23±0．58)％]与非COPD吸烟对照组及非COPD不吸烟对照组比较差异均有统计学意义[(1．52±0．06)％、(1．78±0．06)％, q=5．61、5．38,P均<0．05];LPS刺激后,非COPD吸烟对照组及非COPD不吸烟对照组气道上皮细胞表面TLR4荧光阳性细胞数显著升高[(10．69±0．74)％、(11．28±0．68)％,q=9．58、8．98,P均< 0．05],荧光强度增强,而COPD组则未见明显升高[(11．89±0．89)％,q=1．95,P>0．05]。LPS刺激前,COPD组气道上皮细胞TLR4 mRNA(吸光度值)水平(0．359±0．032)与非COPD吸烟对照组及非COPD不吸烟对照组比较差异均有统计学意义(0．147±0．008、0．152±0．013,q=5．12、4．99,P均< 0．05);LPS刺激后,非COPD吸烟对照组及非COPD不吸烟对照组TLR4 mRNA水平显著升高(0．425±0．037、0．418±0．035,q=4．58、4．65,P均<0．05),而COPD组无显著变化(0．398±0．028, g=0．86,P>0．05)。结论慢性炎症和LPS刺激导致原代培养的COPD患者气道上皮细胞表面TLR4和TLR4 mRNA水平升高可能是COPD发病的一个关键因素。     

Elevated O2 cost of ventilation contributes to tissue wasting in COPD

BACKGROUND AND OBJECTIVES: Thirty to 50% of all COPD patients experience tissue wasting that may be caused by hypermetabolism, but the cause of the perturbed metabolic state is unclear. We hypothesized that the elevated O2 cost of ventilation (O2 COV) may be a contributing factor. All of the data are presented as means (+/-SEM). Ten hypoxemic (a PaO2 of 54+/-3 mm Hg) stable COPD patients (an FEV1/FVC ratio of 42+/-4%) and five healthy control subjects were studied. The patients were divided into two groups based on nutritional status. Group 1 (n = 6) was malnourished (a body mass index [BMI] of 17.6+/-0.7 kg/m2), and group 2 (n = 4) was normally nourished (a BMI of 26.0+/-3 kg/m2). The O2 COV was determined by measuring the change in the oxygen consumption (VO2) and the minute ventilation (VE) caused by CO2-induced hyperventilation. RESULTS AND CONCLUSIONS: Group 1 had an elevated O2 COV when compared to group 2 and the control group, respectively: 16.4+/-1.0 vs 9.7+/-1.0 and 2.4+/-0.2 mL O2/L of VE (p < 0.05). The VO2 at rest was higher for group 1 than for group 2 and the control group, respectively: 4.5+/-0.3 vs 3.1+/-0.5 and 3.4+/-0.2 mL/kg/min (p < 0.05). The resting energy expenditure (REE) % predicted for group 1 was also higher than group 2 and the control group, respectively: 125+/-3% vs 87+/-7% and 97+/-2% (p < 0.05). Significant correlations were observed that implicate the increased O2 COV as a cause of tissue wasting: O2 COV vs BMI (r = -0.79; p = 0.007), O2 COV vs REE % predicted (r = 0.66; p = 0.039), and REE % predicted vs BMI (r = -0.83; p = 0.003). The O2 COV was also correlated with lung function: FEV1/FVC vs O2 COV (r = -0.84; p = 0.002). We conclude that in these COPD patients the O2 COV is associated with an increased metabolic rate which, in turn adversely affects the nutritional status.     

空腹血糖水平与胰岛素抵抗的关系

目的探讨美国糖尿病协会2003年修订的空腹血糖受损(IFG)下限新切点(5·6mmol/L)划分出的中国血糖调节异常(IGR)者是否存在胰岛素抵抗。方法选取糖调节正常者(NGR)9例;以新标准划分的单纯IFG者9例;空腹及糖负荷后血糖均异常的糖调节受损者共20例,其中以新空腹血糖(FPG)切点划分的新联合糖耐量低减(IGT)者10例;以旧FPG切点划分的旧联合IGT者10例;2型糖尿病患者10例。以高胰岛素正葡萄糖钳夹技术测定受试对象的胰岛素敏感性,以静脉葡萄糖耐量试验评估其胰岛β细胞分泌功能。结果(1)新单纯IFG组、新联合IGT组和旧联合IGT组的葡萄糖输注率(GIR)[分别为(7·2±0·8、7·0±1·5、4·8±0·4)mg·kg-1·min-1]明显低于NGR组[(10·3±0·9)mg·kg-1·min-1,P值均<0·05];旧IGT组和DM组[(5·6±1·0)mg·kg-1·min-1]处于相近水平。(2)空腹胰岛素水平在所有IGR组均升高,在DM组下降。(3)新IFG组的胰岛素一、二相分泌量和NGR组相似,但随糖代谢紊乱程度加重,胰岛素一相分泌量进行性下降,而二相分泌水平先逐渐升高,后有所降低。结论(1)新空腹血糖切点划分出的中国IGR者已经出现胰岛素抵抗。(2)随糖代谢紊乱程度的加重,胰岛素分泌缺陷趋于明显。     

Evidence of increased visceral obesity and reduced physical fitness in healthy insulin-resistant first-degree relatives of type 2 diabetic patients

OBJECTIVE: First-degree relatives (FDR) of type 2 diabetic patients are often insulin resistant. Visceral obesity is closely linked to both insulin resistance and type 2 diabetes. We therefore hypothesized that the inheritance of an increased tendency to store fat in visceral fat depots may be a characteristic phenotypic feature in FDR contributing to their insulin resistance. DESIGN AND METHODS: We measured fat distribution in 20 FDR and 14 age-, gender- and body mass index (BMI)-matched controls employing dual energy X-ray absorbtiometry (DEXA)- and computed tomography (CT)-scanning. Insulin-stimulated glucose uptake (ISGU) was determined by a hyperinsulinemic clamp and maximal aerobic work capacity (VO2 max) by a bicycle ergometer test. Baseline lipolysis was measured using [3H]palmitate. The activity level of the hypothalamic-pituitary-adrenal axis was assessed as the 24 h urinary (u)-cortisol/creatinine ratio. RESULTS: All subjects had a normal oral glucose tolerance test (OGTT), but FDR were insulin resistant (ISGU: 6.64+/-0.48 vs 9.12+/-0.98 mg/kg ffm/min, P=0.01). Despite similar BMI (25.2+/-0.5 vs 24.8+/-0.7 kg/m2, P=0.61) and overall fat mass (26.4+/-1.6 vs 24.2+/-2.1%, P=0.41) in FDR vs controls, the amount of visceral adipose tissue was substantially increased (65.9+/-10.0 vs 40.1+/-11.3 cm2, P<0.05) and VO2 max was reduced (52.2+/-3.1 vs 63.3+/-3.9 ml/kg ffm/min, P<0.05) in FDR. Visceral adiposity was inversely correlated with ISGU (FDR: r=-0.52, P<0.05; controls: r=-0.65, P<0.01) and in multiple regression analysis visceral adiposity (P<0.01), VO2 max (P<0.001) and a family history of type 2 diabetes (P<0.05) (r2=0.64) all significantly and independently contributed to the level of ISGU. Baseline palmitate appearance (145+/-10 vs 139+/-15 micromol/min, P=0.74) and the 24 h u-cortisol/creatinine ratio ((24.9+/-1.3 vs 27.4+/-2.0).10(-6), P=0.28) were both comparable in the two groups. CONCLUSION: Healthy but insulin-resistant FDR have enhanced visceral obesity and reduced VO2 max compared with people without a family history of diabetes, despite similar BMI and overall fat mass. Both the visceral adiposity and reduced aerobic fitness are strongly associated with and may contribute to their insulin resistance.