糖耐量受损者胰岛素敏感性及胰岛β细胞功能的研究

目的 研究糖耐量受损(IGT)者的胰岛素抵抗(IR)及胰岛β细胞功能变化。方法 选取正常糖耐量(NGT)、IGT、2型糖尿病(T2DM)者共34例，以高胰岛素正血糖钳夹技术测定IR，行静脉葡萄糖耐量试验评估胰岛β细胞分泌功能。结果 与NGT组相比，IGT组、T2DM组的IR显著升高；IGT组胰岛素第一时相分泌明显下降，空腹胰岛素(FIns)水平及第二时相分泌水平升高；T2DM组IR与IGT组处于同一水平，FIns较NGT组显著减少。结论 由NGT向IGT的演变过程中，IR和胰岛素分泌缺陷共同起作用。     

老年糖耐量低减及新诊断2型糖尿病胰岛素抵抗及胰岛β细胞功能的研究

目的　了解老年糖耐量低减 (IGT)及新诊断的 2型糖尿病 (T2 DM)患者胰岛素抵抗 (IR)及 β细胞的功能状态。方法　对 32例口服葡萄糖耐量正常者 (NGT)、34例 IGT及 45例 T2 DM患者测定口服葡萄糖耐量试验 (OGTT)各点血糖、胰岛素等指标 ,计算 HOMA模型胰岛素抵抗指数 (HOMA- IR)、β细胞功能指数 (HOM- Aβ)、胰岛素敏感性指数 (ISI)并进行统计学比较。结果　 NGT、IGT、T2 DM组 HOMA- IR分别为 0 .74±0 .75、0 .84± 0 .90、1 .2 6± 0 .79,T2 DM与 NGT比较差异有显著性 (P=0 .0 33)。 NGT、IGT、T2 DM组 HOM- Aβ分别为 5.2 7± 0 .88、5.0 4± 0 .64、4.38± 0 .91 ,其中 T2 DM组与 NGT及 IGT组比较差异均有显著性 ,分别为 P=0 .0 0 1及 P=0 .0 2 2。在 OGTT试验中 IGT组 1 2 0 min胰岛素及 1 80min胰岛素显著高于 NGT组 ,分别为 1 2 8.3± 90 .0 m IU/ L,69.6± 49.3 m IU/ L,P=0 .0 1 9;62 .1± 70 .1 m IU/ L,2 7.1± 2 4 .8m IU/ L ,P=0 .0 30。结论　老年 T2 DM表现出显著的 IR及胰岛β细胞功能减退。老年 IGT作为 T2 DM的前期 ,表现出餐后的异常高胰岛素血症     

真胰岛素测定对胰岛β细胞功能和胰岛素抵抗的评价

目的　探讨血清真胰岛素 (TI)与免疫反应性胰岛素 (IRI)在反映胰岛 β细胞功能和胰岛素抵抗 (IR)方面的不同。 方法　测定正常糖耐量 (NGT)组 (75例 )、糖耐量减低 (IGT)组 (43例 )和 2型糖尿病 (T2DM )组 (54例 )的TI(ELISA法 )和IRI(RIA法 )水平 ,计算胰岛 β细胞功能指数 (HOMA β)和IR指数 (HOMA IR)。 结果　 (1 )HOMA βTI在IGT非肥胖组低于NGT非肥胖组 (P <0 0 5) ,T2DM非肥胖组低于NGT和IGT非肥胖组 (均P <0 0 1 ) ;在IGT和T2DM肥胖组低于NGT肥胖组 (均P <0 0 1 )。HOMA βIRI在IGT和T2DM非肥胖组低于NGT非肥胖组 (均P <0 0 5) ;在NGT、IGT和T2DM肥胖组之间无显著差异。(2 )HOMA IRTI和HOMA IRIRI在非肥胖组和肥胖组均显示T2DM有明显IR。结论　在反映胰岛 β细胞功能方面TI优于IRI,在反映IR方面TI与IRI有着相似的意义。     

维吾尔族2型糖尿病家系非糖尿病一级亲胰岛素敏感性及β细胞功能

目的　研究维吾尔族 2型糖尿病 (DM )家系非糖尿病一级亲胰岛素敏感性及 β细胞功能。方法　收集新疆和田地区维吾尔族 2型DM家系 2 1个。在口服糖耐量试验 (OGTT)排除DM的前提下 ,选择先证者的一级亲为观察组 (89人 ) ,选先证者或其血缘亲属的配偶 (78人 ) (除外有DM家族史者 )作为对照组 ;比较两组HOMA β和HOMA IR。 结果　在正常OGTT情况下 ,DM家系一级亲组血浆空腹胰岛素和OGTT 2h胰岛素显著高于对照组 (均P <0 .0 5 )。观察组的HOMA IR高于对照组 (P <0 .0 5 ) ,HOMA β值两组差异无显著性。结论　维吾尔族DM家系非DM一级亲在正常糖耐量情况下已存在高胰岛素血症和胰岛素抵抗 ,但 β细胞功能无明显改变。     

不同糖代谢状态下游离脂肪酸与胰岛素抵抗和胰岛β细胞功能的相关性研究

目的　游离脂肪酸 (FFAs)水平在不同糖代谢状态下对胰岛素抵抗和胰岛 β细胞分泌功能的影响。 方法　选自2 0 0 1- 0 5 2 0 0 3- 11在中国医科大学附属第一医院住院的糖耐量正常 (NGT) 2 8例 ,空腹血糖异常 (IFG)患者 2 0例 ,糖耐量低减 (IGT)患者 2 3例 ,IFG/IGT患者 2 6例 ,2型糖尿病 (T2DM)患者 2 5例。测定各组FFAs水平 ,稳态模型评估胰岛素敏感性 ,HOMA IS及OGTT中糖负荷后 30分钟胰岛素增值与血糖增值的比值评估胰岛 (细胞分泌功能。结果　 (1)IGT组、IFG/IGT组及T2DM组患者FFAs水平明显高于NGT组 ;IFG/IGT组患者FFAs水平明显高于IFG组 ;T2DM组患者FFAs水平低于IGT组。 (2 )IGT组、IFG/IGT组及T2DM组患者HOMA IR均明显高于NGT组。(3)胰岛素分泌功能均以T2DM患者变化最显著。 (4)FFAs与HOMA -IR呈正相关 ;FFAs与胰岛素分泌指数呈负相关 ,FFAs与HOMA β细胞功能指数呈负相关。 结论　FFAs水平与胰岛素抵抗和胰岛素分泌缺陷密切相关     

瑞格列奈对2型糖尿病患者早时相胰岛β细胞功能影响的临床研究

目的探讨瑞格列奈联合口服葡萄糖耐量试验-胰岛素释放试验（OGTT～IRT）评价新诊断的2型糖尿病（T2DM）患者胰岛G细胞功能的价值。方法96例新诊断的T2DM患者在人组时行OGTT试验,其结果作为基线资料。将患者随机分为3组,A组服单次瑞格列奈行OGTT,B组服1周瑞格列奈行OGTT,C组服1周格列本脲行OGTT。测定各时刻真胰岛素（TI）和免疫反应性胰岛素（IRI）,并计算TI／IRI及早时相胰岛素分泌指数△I10／△G30.结果A组和B组服药后30min时TI和TI／IRI较基线明显增加（P〈0．05）,△I10／△G30均较基线显著升高（P〈0．01）;C组服药前后上述指标均无统计学差异。结论瑞格列奈改善早时相胰岛素分泌,其联合OGTT—IRT较常规OGTT—IRT能更真实反映新诊断的T2DM患者胰岛B细胞分泌和储备功能。     

2型糖尿病家系一级亲属非糖尿病同胞血糖、胰岛素和C-肽水平的变化

目的　研究 2型糖尿病 (DM)一级亲属 (一级亲 )成员中有关胰岛素 (INS)作用和分泌的 8个参数水平的变化。方法　以 32 0个 2型DM家系中 347名一级亲非DM非糖耐量低减 (IGT)同胞为观察组 ,32 6名非DM非IGT的同胞配偶为对照组 ,比较两组口服葡萄糖耐量试验 (OGTT)中空腹和 2小时血糖 ,INS、C 肽及胰岛素抵抗稳态模型评估 (HOMA IR)和胰岛 β 细胞功能稳态模型评估 (HOMA B)。结果　总组比较 ,一级亲的HOMA B降低 ,空腹血浆葡萄糖 (FPG)增高 (P分别为0 .0 0 2 6和 0 .0 0 0 2 )。进一步发现差异表现在≥ 40岁亚组 ,除HOMA B和FPG有类似总组比较所见的变化外尚可见到在给于 75克葡萄糖负荷后血糖、INS和C 肽水平均高于对照组 (P分别为0 .0 19、0 .0 30和 0 .0 37)。尤其表现在 40～ 6 0岁和BMI 2 2～ 2 7亚组。结论　 2型DM一级亲非DM、非IGT同胞 ,尤其超过 40岁的成员在出现明显的糖耐量减退前已存在INS作用和分泌的轻度减退     

初诊2型糖尿病患者长期综合干预对糖代谢转归的影响

目的 探讨长期综合干预2型糖尿病(T2DM)患者糖代谢的转归及影响因素.方法 对129例初诊T2DM患者进行为期6年的综合干预,定期随访,监测体重指数(BMI)、腰臀比(WHR)、血压、血脂、空腹血糖(FPG)及餐后2小时血糖(2hPG)、糖化血红蛋白(HbA1c)及空腹胰岛素(FIns),计算胰岛素敏感指数(ISI)及胰岛素抵抗指数(HOMA-IR).随访结束时行75g 口服葡萄糖耐量试验(OGTT),据此将患者分为DM组和非DM (NDM) 组,后者包括正常糖耐量(NGT)、糖耐量受损(IGT)、空腹血糖受损(IFG)及IGT+IFG,分析DM的转归及影响因素.结果 (1)129例T2DM患者6年后有14例(10.9%)转变为NGT,27(20.9%)例转变为IGT、IFG或IGT+IFG,88例(68.2%)仍为DM.(2)NDM组基线时FPG、WHR、甘油三酯(TG)低于DM组;终点时WHR、HbA1c、FPG、2hPG水平低于DM组,高密度脂蛋白胆固醇(HDL-C)高于DM组;两组治疗后BMI、HDL-C的变化值(△BMI、△HDL-C)差异有统计学意义.(3)基线时两组OGTT试验各点胰岛素水平、HOMA-IR及ISI无显著性差异,终点时NDM组OGTT试验0.5h、1h胰岛素水平及ISI高于DM组,HOMA-IR低于DM组;与DM组相比,NDM组治疗后胰岛素的敏感性明显改善.(4)Logistic回归显示OGTT 0.5h胰岛素与DM的缓解呈独立正相关,△HOMA-IR、△BMI与DM的缓解呈独立负相关.结论 (1)长期综合干预可使相当多的T2DM患者获得缓解.(2)控制体重、减轻胰岛素抵抗、恢复早相胰岛素分泌是DM长期缓解的重要因素.     

2型糖尿病患者空腹血清真胰岛素水平和胰岛素抵抗与血脂的关系

目的　探讨 2型糖尿病 (T2DM )患者空腹血清真胰岛素水平、胰岛素抵抗与血脂的关系。　方法　应用BA ELISA法测定正常糖耐量 (NC)组 96例、T2DM组 132例和T2DM伴原发性高血压 (T2DM EH)组 14 8例的空腹血清真胰岛素 (TI)水平 ,酶法检测血脂 ,计算胰岛素抵抗指数(HOMA IR)、β细胞功能指数 (HOMA β)。 　结果　T2DM组及T2DM EH组的甘油三酯 (TG)、HOMA IR高于NC组 ,高密度脂蛋白胆固醇 (HDL C)和HOMA β低于NC组 ,差异均有显著意义 (P<0 0 5 )。T2DM EH组HOMA IR高于T2DM组 ,差异有显著意义 (P <0 0 5 )。T2DM组及T2DM EH组的TG与TI、HOMA IR呈正相关 (P <0 0 1) ,HDL C与TI、HOMA IR呈负相关 (P <0 0 5 )。　结论　T2DM患者空腹血清TI水平与脂代谢异常相关 ,血清TI水平的升高和 (或 )IR的加重均会引起TG升高和HDL C降低。IR与脂代谢异常及高血压的关系较高TI血症更密切。     

肥胖症与糖耐量低减以及2型糖尿病患者的真胰岛素和前胰岛素水平的变化及其意义

肥胖症、糖耐量低减(IGT)和2型糖尿病(T2DM)患者存在高胰岛素血症、胰岛素抵抗(IR)和胰岛素分泌缺陷，但目前并不十分清楚肥胖症、IGT和T2DM患者的血清前胰     

Serum insulin,insulin antibodies and insulin requirement in the first period of insulin treatment in non-insulin resistant diabetics

Summary Twelve insulin-sensitive diabetics were studied for 200 days after the initiation of mixed beef-pork NPH insulin. Normalization of the fasting blood glucose was not accompanied by any elevation in the pre-treatment fasting immunoreactive insulin level. Insulin antibodies appeared in 2 patients on the second week of insulin treatment, in 6 others within 87 days. In 4 patients no antibodies were found 200 days after the start of insulin. The appearance of antibodies was accompanied in two patients by a decrease in insulin requirement, in others there was no change. When antibodies were present, the total maximum insulin binding capacity was 4 to 12 U/1, but the total insulin constituted only 3 to 36% of the binding capacity. Insulin wastage caused by the destruction of the immune complexes was calculated to be 0.35 to 5.6 U/die only, and this explains the negligible effect of insulin antibodies on insulin requirement in non-resistant patients. Presented at the 10th Annual Meeting of the European Association for the Study of Diabetes in Jerusalem, September 11–13, 1974.     

胰岛素的糖基化作用及其与胰岛素抵抗的关系

人胰岛素在体外与不同浓度葡萄糖溶液孵育，利用氯化硝基四唑氮蓝还原反应证实胰岛素能被糖基化；利用抗胰岛素抗体分离３３例Ⅱ型糖尿病患者血清胰岛素，比色测定糖基化胰岛素水平。结果表明：糖尿病患者糖基化胰岛素水平显著升高，且与血糖呈显著正相关，与空腹血胰岛素／血糖比值和糖负荷后曲线下胰岛素／血糖面积比值呈显著负相关。说明糖基化胰岛素水平取决于血糖控制状况。且可能参与胰岛素抵抗的形成。     

Semantics of insulin

The lack of a stringent terminology and a well-defined vocabulary for insulin and related subjects has been a deterrent to solving many of the problems encountered when using insulin in pumps. The same word is sometimes used to describe a number of different phenomena or the same phenomenon is referred to by different words. Thus the word 'insulin', meaning the substance, the protein hormone, is commonly used as a synonym for an 'insulin formulation' for the treatment of diabetes. The 'insulin dimer' can be the covalent or the non-covalent dimer, two very different substances. 'Isoelectric precipitation' is often mistaken for 'fibrillation' and both are referred to as 'aggregation' or 'polymerization'. The word 'crystal' is being used as a synonym for 'particle', and determination of 'the content of insulin' by HPLC is sometimes called a 'bioassay'. The nature and consequences of these pitfalls are discussed, and advice is given on how to avoid them.     

免疫原性与特异性胰岛素检测对胰岛β细胞功能评估的比较

在不同糖耐量者同时检测免疫原性胰岛素(IRI)与特异性胰岛素,发现虽然数值不同,但两种测定方法对于评估不同糖耐量者胰岛β细胞分泌功能及胰岛素敏感性的效果是一致的,提示测定IRI仍有临床实用价值.     

Phenytoin-induced insulin insensitivity

Phenytoin is known to induce hyperglycaemia. The mechanism has generally been considered primarily an inhibition of insulin release. We have recently treated a patient who became hyperglycaemic on phenytoin and whose markedly increased insulin requirements suggested an insulin resistant state. Reduction of the phenytoin dose resulted in amelioration of the hyperglycaemia. In vitro studies of phenytoin in a primary culture system of adipocytes that allowed assessment of both insulin receptor binding and post-binding function showed a 57% reduction in maximum [14C]3-0-methylglucose transport in the presence of phenytoin while having no effect on maximum insulin binding. These results suggest that phenytoin administration can result in insulin insensitivity by inducing a post-binding defect in insulin action.     

Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy

Aims/Introduction

To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.

Materials and Methods

In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.

Results

In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.

Conclusions

The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.     

Effects of new insulin analogues HMR1964 (insulin glulisine) and HMR1423 on insulin receptors

Aims/hypothesis New insulin analogues have been created by amino-acid exchange to provide an improved pharmacokinetic profile. However, safety issues have been raised regarding their use, as amino-acid exchange of insulin may induce altered metabolic and mitogenic effects. For example, the insulin analogue Asp(B10) causes breast cancer in rodents. The aim of this study was to compare two new insulin analogues HMR1964 (Lys[B3],Glu[B29]) (insulin glulisine) and HMR1423 (Gly[A21],His[B31],His[B32]) with regular insulin and the mitogenic analogue Asp(B10).Materials and methods We analysed insulin receptor binding characteristics and dissociation kinetics, as well as insulin-induced receptor auto- and dephosphorylation kinetics, in rat-1 fibroblasts overexpressing the human insulin receptor isoform B. Mitogenic activity was tested in the non-malignant cell line MCF10.Results Regular insulin, HMR1964 and HMR1423 showed no significant differences in receptor association, dissociation and receptor binding affinity, while Asp(B10) displayed markedly increased insulin receptor affinity. All of the analogues induced rapid insulin receptor autophosphorylation, reaching a maximum 10 min after stimulation (10^–9 mmol/l insulin). In contrast, Asp(B10) induced a prolonged phosphorylation and dephosphorylation state of the 95 kDa insulin receptor -subunit. With respect to [³H]thymidine incorporation, the new analogues had similar (HMR1423) or even lower (HMR1964) effects than regular insulin in the mammary epithelial cell line MCF10, while Asp(B10) showed increased [³H]thymidine incorporation.Conclusions/interpretation HMR1964 and HMR1423 displayed the same association, dissociation and insulin receptor affinity kinetics as regular insulin, and might therefore be useful for the treatment of diabetes.     

冠心病与血胰岛素水平及胰岛素敏感性的关系

目的 :探讨冠心病与血胰岛素 (INS)水平及胰岛素敏感性之间的关系。方法 :对 133例冠心病和 77例健康对照者进行血糖 (BG)、血 INS及胰岛素敏感性 (1/ BG× INS)测定。结果 :冠心病组与对照组比较 ,血糖水平无显著性差异 (P >0 .0 5 ) ,而血 INS明显增高 (P <0 .0 5 ) ,胰岛素敏感性明显下降 (P <0 .0 5 )。冠心病组内 ,单纯冠心病组及冠心病并发原发性高血压组相比较 ,两组间血糖、血 INS及胰岛素敏感性均无显著性差异 (P >0 .0 5 )。结论 :冠心病患者存在着高胰岛素血症及胰岛素敏感性下降     

A paradox： Insulin inhibits expression and secretion of resistin which induces insulin resistance

AIM： To confirm whether insulin regulates resistin expression and secretion during differentiation of 3T3-L1 preadipocytes and the relationship of resistin with insulin resistance both in vivo and in vitro. METHODS： Supernatant resistin was measured during differentiation of 3T3-L1 preadipocytes. L6 rat myoblasts and hepatoma cell line H4IIE were used to confirm the cellular function of resistin. Diet-induced obese rats were used as an insulin resistance model to study the relationship of resistin with insulin resistance. RESULTS： Resistin expression and secretion were enhanced during differentiation 3T3-L1 preadipocytes. This cellular differentiation stimulated resistin expression and secretion, but was suppressed by insulin. Resistin also induced insulin resistance in H4IIE hepatocytes and L6 myoblasts. In diet-induced obese rats, serum resistin levels were negatively correlated with insulin sensitivity, but not with serum insulin. CONCLUSION： Insulin can inhibit resistin expression and secretion in vitro, but insulin is not a major regulator of resistin in vivo. Fat tissue mass affects insulin sensitivity by altering the expression and secretion of resistin.     

谷赖胰岛素或赖脯胰岛素联合甘精胰岛素对糖尿病的有效性及安全性

目的 比较谷赖胰岛素和赖脯胰岛素联合甘精胰岛素对糖尿病的有效性、安全性.方法 本研究为多中心、随机、对照研究,包括4周的导人期和12周的治疗期.2007年2月至2008年6月共人选糖尿病患者484例（1型34例,2型450例）,患者糖化血红蛋白（HbA1c）为6.5％～11.0％,之前已接受连续3个月的胰岛素治疗.按3：1随机给予谷赖胰岛素（363例）或赖脯胰岛素（121例）每日3次联合甘精胰岛素每日1次治疗,比较两组治疗12周后HbA1c、血糖变化及低血糖发生情况和治疗满意度.组间数据比较采用ANOVA方法.结果 治疗12周后,谷赖胰岛素和赖脯胰岛素组HbA1c分别由8.7％±1.2％降至7.9％±1.0％及由8.8％±1.2％降至7.9％±1.0％（组内治疗前后比较,t=- 12.55、-8.88,均P＜0.05）.两组空腹血糖（FPG）分别由（8.6±2.8）mmol/L降至（7.7±2.5）mmol/L及由（8.6±2.5） mmol/L降至（7.8±2.2）mmol/L（组内治疗前后比较,t=-6.55、-2.98,均P＜0.05）.谷赖胰岛素组标准餐后2h血糖（2 h PPG）由（10.6±3.8） mmol/L降至（ 10.2±3.7） mmol/L（t=-2.07,P＜0.05）;赖脯胰岛素组2 h PPG治疗前后差异无统计学意义[由（ 10.9±4.0）mmol/L降至（10.4±3.5） mmol/L,t=-1.37,P＞0.05].治疗12周期间,谷赖胰岛素组和赖脯胰岛素组低血糖事件发生率分别为33.9％ （123/363）和34.7％ （42/121）.治疗前后谷赖胰岛素组和赖脯胰岛素组治疗满意度总评分分别由29±5升至31±5及由29±5升至31±4（组内治疗前后比较,t =6.81、4.21,均P＜0.05）.结论 谷赖胰岛素和赖脯胰岛素联合甘精胰岛素治疗糖尿病的临床疗效、安全性及治疗满意度相似.