急性和慢性束缚应激对大鼠内脏敏感性的影响

目的了解急性和慢性求缚应激对大鼠内脏敏感性的影响和持续时间。方法成年SD大鼠随机分为3组：对照组（没有束缚应激），急性部分束缚应激组（单次2h的束缚应激）和慢性部分束缚应激组（连续束缚应激3天，每天2h），通过腹壁回撤反应（AWR）评分评估应激前后不同时间点大鼠对结直肠扩张（CRD）的内脏敏感性。结果①在扩张压力20mmHg和40mmHg时，急慢性束缚应激组的AWR评分均显著高于应激前基础水平（Od）（P〈0．05），但在60，80mmHg压力时各组的AWR评分均无显著差异；②急性束缚组在应激后24h和应激后第7天，AWR评分显著下降（P〈0．05）；③慢性束缚组在末次应激后24h，AWR评分仍维持增高水平，但在第7天时AWR评分回到基础水平。结论急性和慢性束缚应激郜可以导致大鼠内脏敏感性增高，但其作用可能是短暂的。     

Glipizide对非胰岛素依赖型糖尿病患者胰岛素敏感性的影响

用微小模型方法评价了Ｇｌｉｐｉｚｉｄｅ治疗前后６例ＮＩＤＤＭ患者胰岛素敏感性（ＳＩ）的变化，同时观察了糖的自身效应（ＳＧ）、糖的下降速率（ＫＧ）、０－２０分钟曲线胰岛素释放面积、空腹血糖（ＦＢＧ）、空腹胰岛素（ＦＩＮＳ），结果发现ＮＩＤＤＭ患者治疗前后ＳＩ、ＳＧ、ＫＧ、Ｉａｒｅａ ０－２０ｍｉｎ较正常对照组低，ＦＢＧ较对照组高，用Ｇｌｉｐｉｚｉｄｅ治疗２周后，ＦＢＧ降低，ＳＩ、ＳＧ、ＫＧ、Ｉａｒｅ     

非胰岛素依赖型糖尿病和糖耐量低减患者的胰岛素敏感性及其…

为评价糖耐量异常者的胰岛素敏感性改变及其有关因素，对５７２例非胰岛素依赖型糖尿病，６４７例糖耐量低减和５４３名正常对照者进行了研究。结果显示，空腹血浆胰岛素水平和高胰素血症的百分率，在ＮＩＤＤＭ组〉ＩＧＴ组〉正常对照组。胰岛素敏感性指数从大到小的排列顺序为：正常对照组，ＩＧＴ组，新诊断糖尿病组和原诊断糖尿病组。     

急性和慢性束缚应激对大鼠内脏敏感性和神经内分泌的影响

目的了解急性和慢性部分束缚应激对大鼠内脏敏感性以及神经内分泌反应的影响特点和持续时间。方法成年SD大鼠分为对照组(无束缚应激)、急性组和慢性组,通过腹壁回撤反射(AWR)评分评估应激前后大鼠内脏对结直肠扩张(CRD)的敏感性;并通过放免法检测应激前后不同时间点大鼠血浆促肾上腺皮质激素(ACTH)以及皮质酮(CORT)水平。结果①20和40 mm Hg压力扩张时,急、慢性组的AWR评分均显著高于基础水平(0 d),P<0.05;但在应激后第7天AWR评分显著下降,P<0.05。②急性组血浆ACTH和CORT水平显著高于对照组[(25.35±6.03)ng/ml比(7.24±2.97)ng/ml,(312.47±50.76)pg/ml比(97.00±23.33)pg/ml],但束缚应激7 d后,激素浓度[(11.81±5.03)ng/ml和(113.73±24.58)pg/ml]下降至基础水平。③慢性组血浆ACTH和CORT水平[(20.84±2.19)ng/ml和(200.41±78.10)pg/ml]显著高于对照组,且激素水平在束缚7 d后[(19.95±5.31)ng/ml和(162.51±47.08)pg/ml)]仍维持在高水平。结论急性和慢性束缚应激都可导致大鼠内脏敏感性增高,但作用可能是短暂的。急性束缚应激短暂显著提高血浆ACTH和CORT水平,而慢性束缚应激可能长期提高激素水平。     

血脂康对2型糖尿病人胰岛素敏感性的影响

目的探讨血脂康对2型糖尿病人胰岛素敏感性的影响.方法90例2型糖尿病人在原降糖措施的基础上分为三组.三组在治疗前后分别测定病人糖耐量及短时胰岛素耐量试验.A组为血脂康治疗组加用血脂康1.2g/d8周;B组为辛伐汀治疗组加用辛伐他汀10mg/d8周;C组为对照组口服Vitc.结果胰岛素敏感试验A组治疗前后Kitt值分别为0.92±0.27和1.38±0.34,有显著性差异(P＜0.01).B组在治疗前后Kitt值分别为0.93±0.21和1.01±0.19,无显著性差异(P＞0.05).C组治疗前后Kitt值分别为0.93±0.24和0.93±0.2,无显著性差异(P＞0.05).OGTT试验A组显示空腹血糖及餐后各点血糖均明显低于对照组(P＜0.05～0.01).结论血脂康与辛伐他汀均有明显降脂作用,但血脂康有增加2型糖尿病人胰岛素敏感性的效果,也可能血脂康中的其他成分产生降糖作用.     

内质网应激对胰岛素抵抗和糖尿病的影响

内质网(endoplasmic reticulum,ER)应激是细胞应激的重要组成部分,表现为内质网腔内错误折叠或未折叠蛋白的蓄积以及细胞内Ca2+平衡紊乱,与应激细胞的损伤或凋亡直接相关.     

Ⅱ型糖尿病合并高血压对脂代谢及胰岛素敏感性的影响

目的：观察Ⅱ型糖尿病合并高血压对脂代谢及胰岛素敏感性的影响。方法：对20例Ⅱ型糖尿病合并高血压患者和20例Ⅱ型糖尿病无高血压患者的空腹血糖（FBG）,血脂,胰岛素（FINS）,C肽（FCP）,胰岛素敏感指数（ISI）进行对照,结果：Ⅱ型糖尿病合并高血压组与无高血压组比较,甘油三酯（TG）,FINS,FCP水平显著升高（P＜0．05）,高密度脂蛋白（HDL）,ISI水平显著降低（P＜0．05）,结论：Ⅱ型糖尿病合并高血压时脂代谢紊乱及胰岛素抵抗更加明显。     

拜唐苹对胰岛素敏感性影响的临床观察

目的：探讨唐苹对Ⅱ型糖尿病患胰岛素敏感性的影响。方法：分析比较单用美吡哒及美吡哒＋拜唐苹治疗Ⅱ型糖尿病时胰岛素敏感性的变化。结果：美吡哒加拜唐苹组较单用美吡哒组治疗胰岛素敏感性提高显（P＜0．001）,结论：拜唐苹可以明显改善II型糖尿病患对胰岛素的敏感性。     

非胰岛素依赖型糖尿病和糖耐量低减患者的胰岛素敏感性及其相关因素研究

为评价糖耐量异常者的胰岛素敏感性改变及其有关因素，对５７２例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、６４７例糖耐量低减（ＩＧＴ）和５４３名正常对照者进行了研究。结果显示，空腹血浆胰岛素（ＦＩｎｓ）水平和高胰岛素血症的百分率，在ＮＩＤＤＭ组＞ＩＧＴ组＞正常对照组（Ｐ＜０．０１）。胰岛素敏感性指数（ＩＳＩ）［－ｌｎ（ＦＩｎｓ×空腹血糖）］从大到小的排列顺序为：正常对照组、ＩＧＴ组，新诊断糖尿病组和原诊断糖尿病组（Ｐ＜０．０１）。各组肥胖者的ＩＳＩ小于非肥胖者（Ｐ＜０．０１）。单因素相关性分析显示，各组ＩＳＩ与体重指数（ＢＭＩ）呈负相关，与高密度脂蛋白胆固醇呈正相关。糖尿病组和ＩＧＴ组的ＩＳＩ与血压也呈负相关。多元逐步回归分析显示，ＩＳＩ与ＢＭＩ呈负相关，部分与血压、血脂也有相关性。提示糖耐量异常者伴有高胰岛素血症和胰岛素抵抗，ＩＳＩ与血管病变的危险因素有相关性。     

沙格列汀增加老年糖尿病患者胰岛素敏感性的效果

目的 探讨沙格列汀增加老年患者胰岛素敏感性的效果.方法 选择119例存在有肝、肾、心等重要脏器原发疾病老年患者,随机分为两组,观察组59例使用沙格列汀治疗,对照组60例使用二甲双胍治疗,比较治疗前、后患者空腹血糖(FBG)、餐后血糖以及糖化血红蛋白以及餐后胰岛素、C肽水平及胰岛素抵抗指数水平.结果 观察组空腹血糖、餐后血糖以及糖化血红蛋白(HbA1c)均基本恢复正常且显著低于对照组(P＜0.05),观察组胰岛素水平、C肽水平均显著高于治疗前和对照组同时期(P＜0.05),且胰岛素抵抗指数低于治疗前和对照组同时期(P＜0.05).结论 沙格列汀是一种胰岛素增敏剂,但是其具体增加胰岛素使用敏感性的机制尚待进一步探讨.     

短期胰岛素泵强化治疗对新诊断2型糖尿病患者胰岛素分泌和敏感性的影响

目的 探讨短期胰岛素泵强化治疗对新诊断2型糖尿病患者胰岛素敏感性和胰岛素分泌功能的影响.方法 选取2006年6月至2007年2月在本院就诊的新诊断2型糖尿病患者10例进行为期2周的胰岛素泵强化治疗,在治疗前和停泵24 h后分别进行两次静脉葡萄糖耐量试验(IVGTT)和高胰岛素-正葡萄糖钳夹试验.结果 (1)在治疗前所有糖尿病患者均缺乏急性胰岛素分泌(AIR),经2周强化治疗使血糖正常后,所有患者AIR均有了不同程度地恢复[(7.63±4.73 vs 0.83±1.96)mU/L,P＜0.01)].AIR恢复较好的患者略为年轻和肥胖.(2)糖耐量正常志愿者平均葡萄糖输注率(GIR)为(8.26±2.48)mg·kg-1·min-1,而初发2型糖尿病患者在胰岛素泵强化治疗前GIR为(2.30±0.81)mg·kg-1·min-1(与正常者比,P＜0.01),胰岛素泵强化治疗后GIR升高到(5.33±1.43)mg·kg-1·min-1(P＜0.01).GIR升高显著的患者腰围和体重指数低、治疗前的平均血糖高.结论 短期胰岛素泵强化治疗使血糖"正常化",同时可改善胰岛细胞功能,提高胰岛素敏感性.     

新诊断2型糖尿病患者一相胰岛素分泌和胰岛素敏感性评估

目的评估新诊断2型糖尿病患者一相胰岛素分泌与胰岛素敏感性。方法对332例新诊断2型糖尿病患者按照精氨酸刺激试验的结果分为胰岛功能正常组和异常组来评估其胰岛素分泌和胰岛素敏感性的状况。结果（1）胰岛功能正常组的体重、体重指数（BMI）、腰围、臀围、股围、空腹血清真胰岛素和甘油三酯均显著高于胰岛功能异常组（均P〈0．01）；（2）校正性别、年龄、BMI和腰臀比后，胰岛功能正常组的真胰岛素增值（△TI）和胰岛素抵抗指数（HOMA—IR）均显著高于胰岛功能异常组（均P〈0．01）；（3）胰岛素分泌功能正常伴胰岛素抵抗的个体，胰岛素分泌功能正常不伴胰岛素抵抗的个体，胰岛素分泌功能缺陷伴胰岛素抵抗的个体和胰岛素分泌功能缺陷不伴胰岛素抵抗的个体分别占总人数的35．11％、5．02％、29．78％和30．09％。结论2型糖尿病个体可分为单纯胰岛功能异常、单纯胰岛素抵抗及胰岛功能异常伴胰岛素抵抗3类，其诊断和治疗需依据此病理生理状态的评估。     

A comparison of semisynthetic human NPH insulin and porcine NPH insulin in the treatment of insulin-dependent diabetes mellitus

Twenty-two insulin-dependent diabetic patients participated in a double-blind, cross-over study, where treatment with semisynthetic human NPH insulin (Novo Industri) was compared with porcine NPH insulin (Nordisk). Each treatment period lasted 8 weeks. Blood glucose level, glycosylated haemoglobin, insulin requirements, and frequency of hypoglycaemic events were compared. No difference was found in 24-hour blood glucose profiles. Fasting blood glucose level was 8.3 mmol/l during treatment with human insulin and 8.7 mmol/l during treatment with porcine insulin (p less than 0.1). Mean HbA1c was 7.7% at the end of study compared to 9.5% at baseline (p less than 0.01), but this decline in HbA1c was independent of the treatment regimen. Forty-six hypoglycaemic events occurred during treatment with human insulin compared to 39 events during treatment with porcine insulin. No difference was found regarding insulin requirements during the study. It is concluded that semisynthetic human NPH insulin is indistinguishable from porcine NPH insulin with respect to 24-hour blood glucose profile, HbA1c level and insulin dose requirements.     

The insulin sensitivity, glucose sensitivity, and acute insulin response to glucose load in adolescent type 2 diabetes in Taiwanese

BACKGROUND: Insulin sensitivity (SI), glucose sensitivity (SG), acute insulin response to glucose load (AIR), and obesity in adolescent type 2 diabetes patients (young diabetes, YDM) in Taiwan were studied. METHODS: Forty patients diagnosed at <22 years of age were enrolled and divided into non-obese (NOYDM, BMI < 27 kg/m(2)) and obese groups (OBYDM BMI > 27 kg/m(2)). Adult-onset type 2 diabetes patients (ADM) >40 years old (n = 41) and nondiabetic young adults (N) (n = 23) served as controls. Fasting plasma lipids, insulin, and glucose were measured. Homeostasis model assessment was calculated to estimate insulin sensitivity and beta-cell function. A frequent-sampled intravenous glucose tolerance test was performed to evaluate SI, SG, and AIR. RESULTS: SI and AIR were significantly lower in YDM and ADM than in N (0.92 +/- 0.13, 0.8 +/- 0.15 and 3.24 +/- 0.47 x 10(-4)/U/mL for SI; 40.3 +/- 20.3, 107.3 +/- 50.2, 1208 +/- 306.3 uU/min for AIR). SG of YDM and ADM were lower compared with N (0.014 +/- 0.00138, 0.0292 +/- 0.0058 vs 0.034 +/- 0.0086 min(-1) respectively). No difference was noted between YDM and ADM. SI and SG were not different in NOYDM and OBYDM. AIR was higher in OBYDM (83.6 +/- 34.3 vs -7.6 +/- 13.66 uU/min). CONCLUSIONS: YDM had defects in SI, SG, and AIR compared to N, which was similar to the pathophysiology of ADM. The results imply that YDM may be either a different subtype of diabetes or the same type of diabetes as ADM, with severe defects associated with earlier age of onset. OBYDM had higher AIR than NOYDM.     

2型糖尿病患者胰岛素受体酪氨酸激酶活性变化机制的探讨

目的探讨胰岛素受体酪氨酸激酶(TK)活性变化在胰岛素抵抗(IR)发生中的作用。方法采用酶联免疫法研究40例2型糖尿病(DM)患者血中单个核细胞膜上的胰岛素受体TK活性的变化,同时测定空腹血糖(FPG)、HbA1C、空腹胰岛素(FINS)、胰岛素敏感指数、甘油三酯、高密度脂蛋白-胆固醇及其亚型,并用荧光分光分析法测定胞内Ca2+浓度([Ca2+]i)。结果与正常对照组相比,2型DM患者单个核细胞膜上TK活性显著降低[(21.40±9.20)mUvs(9.95±4.40)mU,P<0.01],且TK活性与病程、FPG、HbA1C及FINS呈显著负相关(P<0.05),与胰岛素敏感指数显著正相关(P<0.05);与正常对照相比,2型DM患者单个核细胞内[Ca2+]i显著升高[(193±9)nmol/Lvs(269±33)nmol/L,P<0.01],且与TK活性呈显著负相关(P<0.05)。结论2型DM患者胰岛素受体TK活性降低参与IR的发生,糖尿病时细胞内升高的[Ca2+]i可能是TK活性下降的机制之一。     

Starting insulin in type 2 diabetes: Overcoming barriers to insulin therapy

BACKGROUND:

Several barriers to insulin therapy are encountered by both the providers and the patients with type 2 diabetes mellitus. These barriers include the fear of the needles i.e. number of injections as well as number of times of self blood glucose monitoring, fear of hypoglycemia and weight gain as well as the convenience, compliance and the cost. However, most of these patients are likely to require insulin therapy with increasing duration of the disorder because of the progressive cell failure. Therefore the most important aspect of insulin therapy must revolve around the regimen most suitable and acceptable because of its ability in overcoming these barriers while being effective in attaining and maintaining desirable glycemic control.

METHODS:

Recently published studies using different regimens with combinations of various oral agents and insulins in patients with type 2 DM and manifesting lapse of glycemic control when treated with various oral agents are discussed. Specific attention is paid to the capacity of each individual regimen in overcoming aforementioned barriers.

RESULTS:

Comparative analysis amongst various insulin regimens shows that combination of metformin, and glimeperide with SC administration of basal insulin Lantus required the least daily dose of insulin with least consequential hypoglycemia as well as weight gain. Moreover, the number of injections as well as the number of times of self blood glucose monitoring, were lesser with this regimen with better compliance and more convenience in comparison to other combination insulin regimens.

CONCLUSION:

The insulin regimen with fewest barriers consists of one SC injection of basal insulin lantus in combination with oral agents. However, to be effective, oral agents must include a secretogogue i.e. glimeperide in addition to a sensitizer i.e. metformin and not multiple sensitizers without a secretogogue. Moreover, this regimen apparently is also the most preferred by the patients, and is cost effective.     

冠心病患者胰岛素受体的表达水平及临床意义

目的通过分析人群血清胰岛素受体(InsR)α、β表达水平,探讨其与冠心病(CHD)的相关性及临床意义。方法通过抽签法随机抽取2011年1月至2012年10月门诊及住院人群中CHD患者120例及非CHD对照组118例,并根据是否合并2型糖尿病(T2DM)分为:(1)CHD合并T2DM组61例;(2)CHD非T2DM组59例;(3)非CHD单纯T2DM组60例;(4)非CHD非T2DM组58例。采用酶联免疫分析法测定以上4组人群血清InsR-α、β表达水平,并比较组间差异。结果CHD患者中,合并T2DM组血清InsR-α、β水平均较非T2DM组降低[(0.21±0.02)U/L比(0.35±0.06)U/L,(0.25±0.01)U/L比(0.39±0.02)U/L,均为P<0.05];对照组中,单纯T2DM组血清InsR-α、β水平均较非T2DM组降低[(0.32±0.03)U/L比(0.43±0.01)U/L;(0.40±0.04)U/L比(0.49±0.05)U/L,均为P<0.05]。而CHD合并T2DM组血清InsR-α、β水平较单纯T2DM组降低,CHD非T2DM组患者血清InsR-α、β水平较非CHD非T2DM组降低(均为P<0.05)。结论 InsR表达水平改变可能协同参与了高胰岛素血症及胰岛素抵抗的形成过程,而与CHD的发生发展相关。     

Influence of severe diabetes mellitus early in pregnancy in the rat: effects on insulin sensitivity and insulin secretion in the offspring

Summary We studied the influence of severe diabetes early in pregnancy on insulin sensitivity and insulin secretion in the offspring. Diabetes (blood glucose >20 mmol/l) was induced in female Sprague-Dawley rats before mating. Diabetic dams were insulin treated during the second half of pregnancy (mean blood glucose 10.6 mmol/l). The offspring were reared by foster mothers. Offspring of both sexes were insulin resistant at four and seven months of age as evidenced by normal glucose tolerance after glucose (2 g/kg body weight intraperitoneally) concomitant with higher than normal rises in insulin levels. Regardless of fetal environment the male rats had higher glucose and insulin levels than the female rats. Insulin responses to glucose (27 mmol/l) in vitro in perfused pancreases were not increased by maternal diabetes, male gender or higher age. Conversely responses to 3-isobutyl-1-methylxanthine (1.0 mmol/l) were enhanced by all three conditions. The pancreatic content of insulin was only marginally affected by maternal diabetes. We conclude that severe diabetes during early pregnancy affects glucose homeostasis in the offspring primarily by diminishing insulin sensitivity and that susceptibility to this effect is not sex- or age-dependent.     

关注新诊断2型糖尿病治疗中第一时相胰岛素分泌的重建

在新诊断的2型糖尿病患者，第一时相胰岛素分泌消失但仍可恢复，重建第一时相胰岛素分泌应该成为继血糖达标和预防糖尿病并发症之外的另一重要目标。     

人胰岛素基因转染鼠成纤维细胞致糖尿病大鼠血糖下降效应的研究

目的研究人胰岛素基因表达质粒转染鼠成纤维细胞（Ｌｔｋ－）后对糖尿病大鼠血糖的影响。方法重组的人胰岛素基因表达质粒通过脂质体法转染鼠成纤维细胞（Ｌｔｋ－），经Ｇ４１８选择性筛选获得一株较高胰岛素表达水平的细胞株（Ｌｔｋ－／ＰＲＩ１２），大量扩增，直接注射至糖尿病大鼠腹腔内，并与转染空载体的对照Ｌｔｋ－细胞比较，观察在糖尿病大鼠体内的胰岛素表达及对血糖等变化的影响。结果空载体转染的对照细胞与未转染组相似，无胰岛素表达，植入糖尿病大鼠腹腔后，血糖仍持续稳定在较高水平，体重进行性下降；而接受胰岛素表达载体细胞的糖尿病大鼠，在观察的２１天内血Ｃ肽持续表达，血糖明显下降，体重逐渐恢复。结论人胰岛素基因能成功转染非胰岛β细胞并表达目的基因使血糖水平下降。本研究为进一步开展糖尿病基因治疗研究奠定了基础。