胰岛素自身免疫综合征的诊治

胰岛素自身免疫综合征(IAS)为少见病.通过报道1例IAS并结合国内近20年报道的50例IAS病例,讨论IAS的诊治.临床上对伴有Graves病、服用他巴唑的高胰岛素性低血糖症患者,应检测胰岛素自身抗体,以避免误诊和不必要的手术.     

胰岛素自身免疫综合征一例

胰岛素自身免疫综合征(IAS)是以空腹低血糖或反应性低血糖及内在胰岛素自身抗体(IAA)为特征的罕见自身免疫性疾病,该病国内少见.     

他巴唑对甲亢患者血中胰岛素抗体的影响

胰岛素自身免疫综合征 (IAS)是由日本学者 Harita 1970年首次报道的。截至 1992年底日本统计的资料共 197例。在日本 IAS已成为引起低血糖的第三位原因 [1 ] 。美国、欧洲有少数病例报道。国内至 1998年底共 6例。IAS的临床特征为自发性低血糖而没有使用外源性胰岛素的证据 ,高水平具有免疫活性的胰岛素和存在高滴度的胰岛素自身抗体 (IAA) [2 ] 。 IAA的产生认为与患者使用含巯基 (- SH)的药物有关 ,尤其是他巴唑。在服用他巴唑的甲亢患者血中胰岛素抗体的发生率报道不一 ,Takei发现在 2 0 6例他巴唑治疗的甲亢患者血清中 IAA的检…     

质子泵抑制剂致胰岛素自身免疫综合征一例

胰岛素自身免疫综合征(IAS)是一种少见的自身免疫性内分泌疾病,是由于自身免疫、自身抗体作用引起的一组低血糖综合征。本文报道1例与质子泵抑制剂使用有关的IAS,旨在提醒临床医生在应用该类药物时患者若出现低血糖,需考虑到IAS发生的可能,减少误诊率,使患者得到快速有效的治疗。     

硫普罗宁导致胰岛素自身免疫综合征四例

胰岛素自身免疫综合征（IAS）为血中非外源性胰岛素诱导的高浓度免疫活性胰岛素（IRI）和高效价胰岛素自身抗体（IAA）引起，以反复发作、严重自发性低血糖为特征的一种罕见疾病。以下报告4例硫普罗宁导致的IAS。[第一段]     

胰岛素自身免疫综合征三例

自身免疫性低血糖症（AIH）是低血糖的一种少见原因,其临床特点为自发性低血糖发作、高胰岛素血症及胰岛素抗体或胰岛素受体抗体阳性.根据自身抗体的不同可以分为两种类型：（1）在无外源性胰岛素应用时出现针对内源性胰岛素的抗体（IAA）阳性,称为胰岛素自身免疫综合征（IAS）,1970年由日本Hirata等首次报道,又称Hirata病[1];（2）是针对靶细胞表面的胰岛素受体的抗体（IRA）阳性,称为B型胰岛素抵抗综合征（TBIRS）,较罕见[2],部分可出现低血糖.我院自2009年报道1例IAS后[3],陆续出现数例,现再报告3例IAS患者,以提高临床认识.     

胰岛素自身免疫综合征合并糖尿病酮症酸中毒一例报道

1例胰岛素自身免疫综合征（IAS）患者以DKA为首发症状，使用Ins等降糖治疗后反复出现夜间、清晨空腹低血糖，餐后高血糖，血清IAA及Ins水平持续升高，结合2周前有硫辛酸使用史及HLA-DR4 DRB1*0406（+），诊断为IAS。停用Ins后加用醋酸泼尼松、阿卡波糖并低碳水饮食，患者早餐后血糖降低，未出现低血糖，IAA转阴，空腹及餐后Ins正常。患者有双相情感障碍（BD）病史，BD易合并自身免疫性疾病，既往无并发IAS的报道。     

1例胰岛素自身免疫综合征患者的动态血糖监测

胰岛素自身免疫综合征（IAS）又称自身免疫性低血糖（AIH）,是一种罕见类型的低血糖症,1970年由日本Hirata首次报道,故又称Hirata病。临床以反复发作的低血糖、高胰岛素血症及胰岛素自身抗体（IAA）或胰岛素受体抗体阳性为表现。AIH在日本被列为自发性低血糖症的第3大病因。国内只有少数病例报道,无相关流行病学资料。现将1例IAS患者动态血糖监测结果报道如下。     

胰岛素自身免疫综合征

胰岛素自身免疫综合征是由血中非外源性胰岛素诱导的胰岛素自身抗体及高浓度免疫活性胰岛素所致的自发性低血糖症。其与伴发自身免疫性疾病及应用含巯基药物有关,并与人白细胞抗原高度相关,DRB1*0406可能是主要易感基因;不同人群的发病机制存在异质性。临床上主要特征为未使用外源性胰岛素情况下,出现反复发作性严重低血糖、胰岛素自身抗体滴度明显升高及游离胰岛素升高;主要应与胰岛素瘤鉴别。治疗以停用诱发药物为主,辅以少量多餐、低糖和高纤维饮食,多数患者可自行缓解。必要时应用小剂量泼尼松。     

B型胰岛素抵抗综合征

B型胰岛素抵抗综合征是一种严重胰岛素抵抗状态,是由于循环中存在针对胰岛素受体的抗体所引起的自身免疫综合征,常表现为严重胰岛素抵抗如高血糖、高胰岛素血症、黑棘皮病或顽固性低血糖,大部分患者合并有系统性红斑狼疮等自身免疫性疾病。目前认为胰岛素受体自身抗体的产生是机体免疫调节紊乱所致,而抗体作用的机制未明。B型胰岛素抵抗综合征的确诊有赖于体内胰岛素受体自身抗体的检测。国外文献报道应用免疫抑制剂可以使部分患者病情缓解,但其预后表现为多样化。     

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。