胰岛素抵抗体内检测方法的探讨

目的 探讨几种常用胰岛素抵抗（ＩＲ）体内检测方法的优缺点,并试图进行改良。方法 分别用三种最小模型技术（ＭＭＴ）、三种基础状态法,四种口服葡萄糖耐量试验（ＯＧＴＴ）法对１６例葡萄糖耐量正常（ＮＧＴ）者和１３例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人计算胰钫敏感性指数（ＩＳＩ）,并以经典ＭＭＴ得出的ＩＳＩ为标准,其余方法得出ＩＳＩ与之进行比较和相关分析。结果 除空腹血糖、空腹胰岛素比值（ＦＳＧ／ＦＩｎ     

胰岛素抵抗及胰岛素分泌功能对肝硬化糖代谢的影响

为探讨肝硬化患者胰岛素抵抗及胰岛素分泌功能和糖代谢的改变。地３０例肝硬化２和２６例正常人进行口服葡萄糖耐量及胰岛素释放试验,以Ｈｏｍａ模型计算胰岛素抵抗指数（ＩＲ）及胰岛β细胞功能指数（ＨＤＣＩ）,并对结果进行分析。结果显示,肝硬化组糖耐是较对照组显著降低,血清胰 素水平增高,并呈现释放延迟,ＫＩＲ有ＨＤＣＩ指数高于对照组。结论：肝硬化患者存在胰同素抵抗、肝源怀糖耐量异常及内源性高胰岛素血症或胰岛     

真胰岛素测定在分析β细胞功能及胰岛素敏感性的意义初探

目的探讨真胰岛素（Ｔｒｕｅｉｎｓｕｌｉｎ，ＴＩ）测定在分析胰岛β细胞功能及胰岛素敏感性中的意义。方法采用双位点夹心放大酶联免疫分析法（ＢＡＥＬＩＳＡ）及其它方法对４３例糖耐量正常者（ＮＧＴ）、２０例糖耐量低减者（ＩＧＴ）及４７例２型糖尿病（ＤＭ）患者进行血清ＴＩ等的测定，初步分析其胰岛β细胞功能及胰岛素敏感性。结果肥胖的２型ＤＭ组血清空腹ＴＩ水平不高（Ｐ＞０．０５），而免疫反应性胰岛素（ＩＲＩ）则明显升高（Ｐ＜０．０１），ＯＧＴＴ３０分钟ＴＩ水平明显低于ＮＧＴ组（Ｐ＜０．０１）。用ＴＩ计算胰岛素释放指数，ＮＧＴ＞ＩＧＴ＞２型ＤＭ；敏感指数，ＮＧＴ与ＩＧＴ均明显高于２型ＤＭ（Ｐ＜０．０１）；而用ＩＲＩ计算胰岛素释放指数和敏感指数仅在ＮＧＴ与２型ＤＭ组间有显著差异（Ｐ＜０．０１）。结论２型ＤＭ患者的高胰岛素血症可能是高胰岛素原血症；ＴＩ测定较ＩＲＩ更能确切地评价β细胞功能及胰岛素敏感性     

减少样本数的Bergman最小模型技术在胰岛素抵抗综合征中？…

目的 研究单纯性肥胖、糖耐量减退（ＩＧＴ）和２型糖尿病（ＤＭ）患者胰岛素抵抗的发病机制。方法 用减少样本数的Ｂｅｒｇｍａｎ最小模型技术结合多样本静脉葡萄糖耐量试验分别测定正常人、单纯性肥胖、ＩＧＴ和２型ＤＭ患者胰岛素敏感性指数（ＳＩ）、葡萄糖自身代谢效能（ＳＧ）及胰岛β细胞分泌功能,同时测定体重指数（ＢＭＩ）和腰臀比（ＷＨＲ）。结果 正常组的ＳＩ和ＳＧ均明显高于ＩＧＴ和２型ＤＭ组,但与肥胖组相比,     

2型糖尿病脓系胰岛素分泌功能的研究

目的 探讨胰岛素抵抗（ＩＲ）和胰岛细胞功能障碍在２型糖尿病（ＤＭ）发病中的作用，方法２ＤＭ家系中，对部分成员进行口服葡萄糖耐量试验（ＯＧＴＴ）〈按ＷＨＯ标准将家系成员ＤＭ一级亲属正常组（１０６例，糖耐量低减组（ＩＧＴ）组（３９例），新诊断ＤＭ组（６３例）和原诊断ＤＭ组（８３例，病程１年以上）〉计算各组成员的胰岛素敏感性指数（ＩＳＩ）以及有遍初期分泌功能的指数，民无ＤＭ家族史的健康人（５３例）相比较     

胰岛素抵抗是糖耐量正常人群糖耐量恶化的重要危险因素

目的 探讨胰岛素抵抗和胰岛素分泌对糖在耐量正常人群糖耐量恶化的影响。方法 以口服葡萄糖耐量试验（ＯＧＴＴ）做人群普查一，确定糖耐量正常者（ＮＧＴ）（空腹血糖（ＦＰＧ）〈５．８ｍｍｏｌ／Ｌ及２小时血糖（ＰＧ２ｈ〈６．７ｍｍｏｌ／Ｌ＿１２５例，测定血浆胰岛素。６年后随访再以ＯＧＴＴ确定盲人 群糖耐量状态，以稳态模型（Ｈｏｍａ Ｍｏｄｅｌ）公式评估胰岛素抱搞（ＩＲ）、胰岛素分泌功能（ＩＳ），并分析其对糖     

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。     

233例非糖尿病人群空腹血浆胰岛素水平预测体重增加的？…

目的 探讨非糖尿病人群胰岛素抵抗及血浆胰岛素水平对体重增加的影响。方法：人群调查中以口服葡萄糖耐量试验（ＯＧＴＴ）筛选的非糖尿病者２３３例（正常糖耐量（ＮＧＴ）１３４例,糖耐量低减（ＩＧＴ）９９例）,随访观察６年,以多因素回归分析初庐互岛素水平、胰岛素抵抗与体重增加的关系。结果 在总组,体重增加与初访体重指数（ＭＢＩ）呈显著负相关（Ｐ＝０．００３）,与胰岛素敏感指数及家腹血糖水平呈显著正相关（Ｐ＝     

空腹血胰岛素、葡萄糖比值作为β细胞功能指数的可能性

目的探讨空腹血浆胰岛素、葡萄糖比值（ＦＩＮＳ／ＦＰＧ）作为群体研究胰岛β细胞功能指数的可能性，并与文献中其他指数比较。方法在糖耐量正常者（ＮＧＴ）１８１例，糖耐量低减者（ＩＧＴ）２８１例测定空腹及服葡萄糖７５克后１小时、２小时静脉血浆葡萄糖及胰岛素。按服糖后２小时血糖水平依次递增０．５５６ｍｍｏｌ／Ｌ，再将ＩＧＴ分为血糖从低到高６个亚组，以ｔ检验及方差检验判定ＦＩＮＳ／ＦＰＧ及文献中常用五种胰岛β细胞功能指数分辨ＮＧＴ与ＩＧＴ，及ＩＧＴ血糖水平不同亚组间β细胞功能差别的能力。结果①ＯＧＴＴ１小时血浆胰岛素、葡萄糖比值（ＩＮＳ１／ＰＧ１），ＯＧＴＴ胰岛素、血糖增值比值（△ＩＮＳ／△ＰＧ）以及Ｈｏｍａｍｏｄｅｌ中的２０×ＦＩＮＳ／（ＦＰＧ３．５）都能分辨从ＮＧＴ、ＩＧＴ的β细胞功能变化，却无一能辨认ＩＧＴ血糖水平不同亚群的β细胞功能差别。②调整胰岛素敏感性的影响后，它们则具有了各种不同程度的分辨上述人群β细胞功能变化趋势的能力。结论①使用上述β细胞功能指数必须调整胰岛素敏感性的影响；②ＦＩＮＳ／ＦＰＧ可在流行病研究中评估β细胞功能，其分辨能力不逊于Ｈｏｍａｍｏｄｅｌ中的２０×ＦＩＮＳ（ＦＰＧ３．５）。     

胰岛素抵抗、胰岛素分泌功能对Ⅱ型糖尿病发生的影响

目的探讨中国非糖尿病人群中胰岛素抵抗、胰岛素分泌功能对糖尿病发生的影响。方法以Ｈｏｍａ模型的胰岛素抵抗指数（ＩＲ）＝ＦＩＮＳ／２２５ｅ－ｌｎＦＰＧ（ＦＩＮＳ为空腹胰岛素，ＦＰＧ为空腹血糖）及β细胞功能指数（ＨＢＣＩ）＝ＦＩＮＳ×２０／（ＦＰＧ－３５），对４０９例非糖尿病者６年随访资料进行糖尿病发病危险因素的比例风险模型分析，再以胰岛素敏感性指数（ＩＡＩ）＝１／（ＦＰＧ×ＦＩＮＳ）、胰岛素分泌功能指数（ＩＳ）＝ＦＩＮＳ／ＦＰＧ这对更简单的指数进行同样分析，并与前者比较。结果以Ｈｏｍａ模型的ＩＲ、ＨＢＣＩ分析显示，排除口服葡萄糖耐量试验２小时血糖、体重指数因素影响后，ＩＲ与糖尿病正相关（Ｐ＜００５），ＨＢＣＩ与糖尿病负相关（Ｐ＜０．０１），生活方式干预有利于减少糖尿病发病危险。与以ＩＡＩ＝１／（ＦＩＮＳ×ＦＰＧ）、ＩＳ＝ＦＩＮＳ／ＦＰＧ分析结果相似。结论（１）胰岛素抵抗及胰岛素分泌功能差是Ⅱ型糖尿病发病危险因素；（２）仅涉及空腹血糖及空腹胰岛素的Ｈｏｍａ模型在流行病研究中可用于评价胰岛素抵抗及β细胞功能，ＩＡＩ＝１／（ＦＰＧ×ＦＩＮＳ）、ＩＳ＝ＦＩＮＳ／ＦＰＧ可在分析中代替Ｈｏｍａ模型     

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。     

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.     

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.     

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。     

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.     

罗格列酮对2型糖尿病患者血压的影响

目的 观察胰岛素增敏剂罗格列酮治疗2型糖尿病伴高血压患者，评价其降压作用，探讨其降压机理。方法 32例2型糖尿病患者按血压分组，口服罗格列酮(文迪雅)4～8mg／d，共8w，计算胰岛素敏感指数和抵抗指数。结果 罗格列酮分别降低了两组的血压水平，胰岛素敏感指数升高，抵抗指数降低。结论 罗格列酮治疗2型糖尿病伴有高血压的患者的时候，在降低血浆胰岛素水平、改善IR的同时，能够明显降低血压。     

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。