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。     

血管内皮功能与肥胖高血压发生的相关性随访研究

目的探讨血管内皮功能障碍与肥胖高血压发生的关联性。方法对2000年石家庄市部分社区居民健康检查筛查出的体重指数≥25kg／m^2的单纯肥胖者583例（男376例，女207例）进行内皮依赖性血管舒张（EDD）功能以及体重指数（BMI）、腰围（WC）、腰臀比（WHR）、血压、血脂、空腹血糖（FPG）和胰岛素（Fins）、胰岛素抵抗指数（HOMA—IR）测定。并在7年后对上述人群进行随访，共随访到524例，男356例，女168例。结果7年内共发生高血压者203人，占随访对象的38．74％。初访时伴有内皮功能障碍的297例中发生高血压者158例，占53．20％，初访时内皮功能正常者134例，发生高血压者45例，占33．58％，前者显著高于后者（P〈0．01）。按照随访时有无高血压分组后比较，肥胖高血压组初访时WC、WHR、甘油三酯（TG）、Fins和HOMA—IR均显著高于肥胖非高血压组（P〈0．05或P〈0．01）。肥胖高血压组EDD显著低于肥胖非高血压组（P〈0．01）。Logistic分析显示，EDD、HOMA—IR与肥胖高血压发生密切相关。结论血管内皮功能障碍可能是导致肥胖高血压发生的重要原因，与胰岛素抵抗共同参与肥胖高血压的发病机制。     

内皮功能障碍与胰岛素抵抗和肥胖关系研究的7年随诊观察

目的观察血管内皮功能、胰岛素抵抗（IR）和肥胖之间的动态关系。方法对583例单纯性肥胖者进行7年随访,共计431例纳入随访分析。按照初访时内皮依赖性血管舒张功能（EDD）、胰岛素抵抗指数（HOMA-IR）以及随访时减重与否分组,对各组随访前后EDD、HOMA-IR和体脂进行比较分析。结果（1）与初访时比较内皮功能异常组7年后腰臀比和HOMA—IR明显升高（P〈0．05）,EDD显著降低（P〈O．05）,内皮功能正常组体重指数较前降低（P〈O．05）,HOMA—IR和EDD无显著变化。（2）无论初访或随访IR组腰围和HOMA—IR均明显高于非IR组（P〈0．05或P〈0．01）,但EDD在初访时两组无显著差异,随访时前者明显低于后者以及本组初访时（均P〈0．05）。（3）初访时,未减重组HOMA_IR高于减重组（P〈0．05）,EDD低于减重组（P〈0．01）。7年后未减重组体重指数、腰围和HO-MA—IR均明显高于减重组（P〈0．05或P〈0．01）,EDD明显低于减重组（P〈0．01）。且与初访时比较,随访时未减重组HOMA-IR显著升高（P〈O．05）,EDD显著降低（P〈0．05）。减重组HOMA-IR、EDD无明显变化。结论内皮功能障碍可能是导致超重和肥胖相关的IR的病因,两者也是影响减重效果的原因之一,但前者可能与减重关系更密切。     

初诊2型糖尿病胰岛素抵抗与血管内皮功能的关系

目的探讨初诊2型糖尿病患者胰岛素抵抗(IR)与血管内皮功能的关系。方法初诊2型糖尿病患者分为IR组34例和非IR组31例,另设非糖尿病对照组30例。采用高分辨率血管外超声法检测肱动脉血管血流介导的内皮依赖性血管舒张功能(EDD)和硝酸甘油介导的内皮非依赖性血管舒张功能(GNT),并运用稳态模式评估方法评价IR。结果IR组和非IR组的EDD较对照组显著降低,分别为6.36%±2.92%、7.70%±3.13%和9.15%±3.46%(P<0.01和P<0.05),IR组又低于非IR组(P<0.05)。EDD在IR组与WHR、HOMA-IR呈负相关(P<0.01),在非IR组与BMI呈正相关(P<0.01),与WHR、HbA1C及TG呈负相关(P<0.05和P<0.01),与IR无明显相关性,而在对照组仅与WHR呈负相关(P<0.05)。结论在以IR为始动因素引发的糖尿病中内皮依赖性舒张功能障碍可能与IR共同参与了糖尿病的发生,而在以胰岛素分泌缺乏为主引发的糖尿病中,内皮功能障碍可能主要继发于高血糖、高血脂或腹型肥胖。     

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。     

空腹血糖受损人群胰岛素抵抗和胰岛β细胞功能特点分析

目的　探讨我国空腹血糖受损 (IFG)人群胰岛素抵抗 (IR)和胰岛 β细胞功能的特点。 方法　根据口服 75g葡萄糖耐量试验将 13 0 45例≥ 2 5岁的中国人群分为糖耐量正常 (NGT)组 ,IFG组 ,糖耐量低减 (IGT)组和IFG/IGT组 ,利用HOMA胰岛素抵抗指数 (HOMA IR)、HOMAβ细胞功能指数 (HBCI)、第 1和第 2时相胰岛素释放指数等进行组间比较和多因素分析。结果　 (1)与NGT组相比 ,IFG组体重指数、腰臀围比值、空腹胰岛素、血清甘油三酯、血压、HOMA IR明显升高 ,而HBCI、第 1和第 2时相胰岛素释放指数明显降低 (P <0 .0 1～P <0 .0 0 1)。Logistic回归分析显示 :HOMA IR与IFG发生的一致性高达 0 .66～ 0 .79(均P <0 .0 0 1)。 (2 )与IGT组相比 ,IFG组OGTT 2h胰岛素水平显著低于IGT(P <0 .0 0 1)。Logistic回归分析显示 :HOMA IR、第 1和第 2时相胰岛素分泌指数与IFG发病显著正相关 ,HBCI与IFG发病显著负相关 ,各方程预测IFG发生的一致性高达 0 .5 6～ 0 .74(均P <0 .0 0 1)。结论　IFG者空腹状态下的胰岛素敏感性和 β细胞功能均较NGT和IGT者差 ,而糖负荷后的胰岛素分泌状态比NGT者差 ,但明显好于IGT者 ,因此 ,IFG者可能存在空腹及餐后IR和 β细胞功能的分离状态 ,是一组有别于IGT的糖稳态受损人群。     

2型糖尿病患者血浆酰化刺激蛋白和C3水平与胰岛素抵抗和血脂的相关性

目的　了解 2型糖尿病 (T2DM)患者血浆中酰化刺激蛋白 (ASP)及补体C3 与胰岛素抵抗 (IR)及血脂紊乱的相关性 ,探讨ASP与C3 可能参与IR的机制。　方法　根据体质指数 (BMI)将82例T2DM患者分为肥胖组 (BMI≥ 2 5kg/m2 )及非肥胖组 ,同时将 10 5名非糖尿病者分为单纯肥胖(Ob)组 (BMI≥ 2 5kg/m2 )及正常体重对照组。测定ASP、游离脂肪酸 (FFA)、空腹胰岛素 (FIns)、C3 ,空腹血糖 (FPG)、甘油三酯 (TG)、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)和胰岛素抵抗指数 (HOMA IR)。　结果　非肥胖糖尿病组 [( 6 7± 38)nmol/L]及Ob组患者ASP水平 [( 6 0± 2 9)nmol/L]显著高于对照组 [( 4 5± 2 1)nmol/L],肥胖糖尿病组ASP水平 [( 5 7± 33)nmol/L]也高于对照组 ,但差异无显著意义。肥胖糖尿病组C3 水平 [( 2 8± 1 2 ) g/L]显著高于对照组 [( 1 9± 0 9) g/L]及Ob组 [( 2 1± 0 9) g/L],Ob组ASP/C3 率 ( 0 7± 0 1)显著高于对照组( 0 5± 0 4 )。相关分析结果显示 ,ASP与BMI、TC、FFA及FPG呈正相关 (r =0 191,P =0 0 0 9;r=0 14 6 ,P =0 0 4 9;r =0 132 ,P =0 0 5 ;r =0 14 0 ,P =0 0 5 ) ;C3 与FPG、FIns及HOMA IR呈正相关 (r =0 2 12 ,P =0 0 0 3;r =0 2 6     

胰岛素分泌功能与内皮依赖性血管舒张功能相关

对正常体重组 (81例 ) ,单纯肥胖组 (14 0例 )和肥胖伴高血糖组 (97例 )的观察结果显示 :β细胞功能与内皮依赖性血管舒张功能 (EDV)在肥胖伴高血糖组呈显著正相关 (r =0 .5 2 ,P <0 .0 0 1) ,而在单纯肥胖组和正常体重组未显示相关性。EDV障碍可能是导致肥胖者 β细胞功能障碍的重要危险因素。     

血管内皮功能与血糖、胰岛素水平及心血管危险因素的相关性

目的 研究超重肥胖者血管内皮功能与血糖、胰岛素水平及心血管病危险因素的关系。方法 367例超重肥胖者被分成2型糖尿病组、糖耐量减低组、空腹血糖受损组、正常糖耐量组及单纯超重肥胖组，并与66例正常体重者对照。测定血管内皮依赖性舒张功能(血流介导)和内皮非依赖性舒张功能(硝酸甘油介导)，并测定体脂、血压、血糖、血脂和胰岛素抵抗指数(HOMA-IR)。结果 超重肥胖者的内皮依赖性舒张功能显著降低，合并代谢异常者降低更显著。血管内皮依赖性舒张功能与腰臀比、收缩压、HOMA-IR呈显著负相关。结论 超重肥胖者血管内皮功能受损，腰臀比、收缩压及HOMA—IR是影响内皮功能的主要因素。     

初诊2型糖尿病患者尿微量白蛋白与血管内皮功能的关系

目的观察伴或不伴微量白蛋白尿（MAU）初诊2型糖尿病患者血管内皮功能情况,探讨MAU与血管内皮功能的关系及其发生机制。方法将初诊2型糖尿病患者依据24小时尿微量白蛋白排泄率分为伴微量白蛋白尿组（MAU组）、不伴微量白蛋白尿组（NA组）,MAU组34例,NA组96例,以50例正常受试者作为对照;采用彩色多普勒超声技术测定反应性充血时血流介导肱动脉舒张功能（FMD）和硝酸甘油介导的肱动脉舒张功能（NMD）。并测定空腹血糖（FBG）、糖化血红蛋白（HbA1c）、空腹胰岛素、血脂,并依据空腹血糖、空腹胰岛素计算胰岛素抵抗指数（HOMA—IR）。结果MAU组、NA组的FBG、甘油三酯（TG）、总胆固醇（TC）、HbA1c、HOMA—IR高于对照组（P〈0．01）;MAU组的FBG、TG、TC、HbA1c、HOMA—IR高于NA组（P〈0．01）。与对照组相比,MAU组、NA组的FMD均受损,但MAU组较NA组受损更为明显,三组间比较NMD无明显差异。结论初诊2型糖尿病患者已存在内皮功能受损,不伴MAU的患者血管内皮功能受损较轻,伴MAU的患者血管内皮功能受损更为严重,其发生与伴MAU的患者血糖、血脂紊乱程度及胰岛素抵抗程度更为严重有关。     

New insights into the signaling system and function of insulin in fish

Fish have provided essential information about the structure, biosynthesis, evolution, and function of insulin (INS) as well as about the structure, evolution, and mechanism of action of insulin receptors (IR). INS, insulin-like growth factor (IGF)-1, and IGF-2 share a common ancestor; INS and a single IGF occur in Agnathans, whereas INS and distinct IGF-1 and IGF-2s appear in Chondrichthyes. Some but not all teleost fish possess multiple INS genes, but it is not clear if they arose from a common gene duplication event or from multiple separate gene duplications. INS is produced by the endocrine pancreas of fish as well as by several other tissues, including brain, pituitary, gastrointestinal tract, and adipose tissue. INS regulates various aspects of feeding, growth, development, and intermediary metabolism in fish. The actions of INS are mediated through the insulin receptor (IR), a member of the receptor tyrosine kinase family. IRs are widely distributed in peripheral tissues of fish, and multiple IR subtypes that derive from distinct mRNAs have been described. The IRs of fish link to several cellular effector systems, including the ERK and IRS-PI3k-Akt pathways. The diverse effects of INS can be modulated by altering the production and release of INS as well as by adjusting the production/surface expression of IR. The diverse actions of INS in fish as well as the diverse nature of the neural, hormonal, and environmental factors known to affect the INS signaling system reflects the various life history patterns that have evolved to enable fish to occupy a wide range of aquatic habitats.     

胰岛素治疗使糖尿病大鼠的胰岛素抵抗逆转

链脲佐菌素引起的糖尿病大鼠用胰岛素治疗6天后,治疗组(n=4)与未治疗组(n=20)比较:(1)体重和血清胰岛素浓度显著增加,而摄食量,饮水量和血糖均显著降低;(2)脂肪细胞膜胰岛素结合率显著降低,其胰岛素受体数目减少但受体亲和力没有改变;(3)基础(不加胰岛素时)和胰岛素刺激的脂肪细胞葡萄糖氧化均显著增加。提示胰岛素治疗虽使靶细胞上胰岛素受体数目减少,但可显著提高靶细胞对胰岛素的反应性,即可使受体后胰岛素抵抗减轻。     

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.     

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.     

Insulin-derived Amyloidosis and Poor Glycemic Control: A Case Series

Objectives

Insulin-derived amyloidosis is a rare skin-related complication of insulin therapy. The purpose of this study was to show the effects of insulin-derived amyloidosis on blood glucose levels, insulin dose requirements, and insulin absorption.

Methods

Seven patients were found to have insulin-derived amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical characteristics and insulin therapy of the 7 patients were investigated. Insulin absorption was studied by comparing the serum insulin levels after insulin injections into insulin-derived amyloidosis sites versus injections into normal sites in 4 patients.

Results

When the insulin-derived amyloidosis was discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin dose was 57 units. After changing the injection sites to avoid the insulin-derived amyloidosis, the blood glucose concentrations improved, and the mean daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal sites (P = .030).

Conclusions

Insulin-derived amyloidosis caused poor glycemic control and increased insulin dose requirements because of impairments in insulin absorption.     

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.     

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。     

链脲佐菌素糖尿病大鼠的胰岛素受体结合、胰岛素介体释放和葡萄糖氧化

作者测定了链脲佐菌素引起的糖尿病大鼠脂肪细胞膜对胰岛素特异结合率、肝细胞膜胰岛素介体释放和脂肪细胞葡萄糖氧化。结果表明:(1)糖尿病大鼠脂肪细胞膜对胰岛素特异结合率较正常大鼠显著增加,其胰岛素受体亲和力没有改变,但受体数目增加;(2)大鼠肝细胞膜加胰岛素诱导时,糖尿病鼠肝膜释放的抑制腺苷酸环化酶活力的胰岛素介体量较正常大鼠显著减少;(3)在糖尿病大鼠,基础的和胰岛素刺激的脂肪细胞葡萄糖氧化较正常大鼠显著降低。提示胰岛素介体释放量减少可能是引起受体后胰岛素抵抗的原因之一。