Suicid mit Insulin und Nachweis des Insulins an der Leiche

Zusammenfassung Es wird über einen 50jährigen Diabetiker berichtet, welcher sich in suicidaler Absicht insgesamt 1080 E Insulin Novo lente s.c. injiziert hatte und innert 26 Std verstorben war. Post mortem war der Nachweis des exogenen Hyperinsulinismus durch quantitative Bestimmung des freien Insulins im Serum und an den Injektionsstellen gelungen.     

Insulin precipitation in artificial infusion devices

Summary Precipitation of insulin is a problem with mechanical insulin infusion devices. Therefore conditions affecting insulin precipitation have been studied in a recirculating system using a peristaltic pump. Acetate buffer favoured precipitation and a pH of 2, 3 or 8 resulted in no less (and often more) precipitation than a pH of 7 using either acetate or phosphate buffer. However, no precipitation occurred in a phosphate buffered neutral preparation after ten days of pumping through tubing pretreated with EDTA. In comparison at pH 7, using acetate buffer with untreated tubing, more than 95% of insulin was precipitated in ten days. A heavy metal-insulin association appears to be a major factor in the precipitation. However, some formation of insulin fibrils is probable as the precipitate is autocatalytic and partially acid insoluble. Phosphate buffered highly purified porcine insulin is suitable for relatively prolonged infusion if metal ion contamination of the delivery system is minimised.     

Insulin allergy. Clinical and immunological effects of specific desensitization

Summary Five patients with insulin allergy were desensitized with porcine insulin according to the method of Urbach and Gotlieb. The diagnosis of insulin allergy was based on clinical manifestations, positive skin tests, and, moreover, on positive Prausnitz-Küstner (P.K.) reactions in 2 cases. Successful desensitization was obtained in 3 cases. Insulin antibodies were detected by the method of immunoautoradiography using¹³¹J-insulin. Before desensitization presence of IgG antibodies was found in 3 patients, and in 2 patients IgA antibodies were found also. The P.K. reactions were positive in patients whose sera contained IgA antibodies. During desensitization a transient appearance of macroglobulins binding¹³¹J-insulin was observed. After desensitization positive immediate skin responses to porcine and bovine insulin were found to persist. At the same time the delayed responses and the P.K. reaction to porcine insulin were reversed, although the same reactions to bovine insulin remained positive.

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Zusammenfassung Fuenf Patienten mit Insulin-Allergie wurden mit Schweine-Insulin laut der Methode von Urbach und Gotlieb desensibilisiert. Die Diagnose einer Insulin-Allergie wurde auf der Grundlage der klinischen Anzeichen, der Positivitaet der Haut-Reaktionen und, in 2 Faellen, auf der Basis der Prausnitz-Küstner-Reaktionen gestellt (P.K.). In 3 Faellen wurde Desensibilisierung erzielt. Die Anwesenheit von Insulin-Antikoerpern wurde mit der immunoautoradiographischen Methode unter Verwendung von¹³¹J-Insulin verfolgt. Vor der Desensibilisierung wurde bei 3 Patienten die Anwesenheit von IgG-Antikoerpern festgestellt; bei 2 wurden auch IgA-Antikoerper identifiziert. Eine positive P.K.- Reaktion wurde bei Patienten beobachtet, deren Seren IgA-Antikoerper enthielten. Waehrend der Desensibilisierung wurde das voruebergehende Auftreten von Makroglobulinen beobachtet, die imstande waren, das¹³¹J-Insulin zu binden. Nach der Desensibilisierung wurde das Andauern der Positivitaet der sofortigen Hautreaktionen auf Schweine- und Rinderinsulin festgestellt. Gleichzeitig waren die verspaeteten Antworten sowie die P.K.-Reaktion auf Schweine-Insulin umgekehrt, obwohl die gleichen Reaktionen auf Rinderinsulin positiv blieben.

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Resumen Cinco pacientes que padecían de alergia a la insulina han sido desensibilizados con insulina porcina según el método de Urbach y Gotlieb. El diagnóstico de alergia a la insulina ha sido puesto teniendo en cuenta las manifestaciones clínicas, el positivismo de las reacciones cutáneas, y, en 2 casos, las reacciones de Prausnitz-Küstner (P.K.). En 3 casos se ha obtenido desensibilización. La presencia de anticuerpos anti-insulina ha sido puesta en evidencia con el método inmunoautoradiográfico, empleando insulina¹³¹J. Antes de la desensibilización, la presencia de anticuerpos IgG ha sido hallada en 3 pacientes, mientras que en 2 han sido demostrados también anticuerpos IgA. Una reacción de P.K. positiva ha sido observada en pacientes cuyos sueros contenían anticuerpos IgA. Durante la desensibilización se ha observado aparición transitoria de macroglobulinas capaces de ligar la insulina¹³¹J. Al cabo de la desensibilización se ha notado la persistencia del positivismo a las respuestas cutáneas inmediatas a la insulina porcina y bovina. Al mismo tiempo, las respuestas retardadas y la reacción de P.K. a la insulina porcina cstaban invertidas, no obstante que las mismas reacciones a la insulina bovina hubieran quedado positivas.

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Resume Cinq patients atteints d'allergie à l'insuline ont été désensibilisés par de l'insuline de porc selon la méthode d'Urbach et Gotlieb. Le diagnostic d'allergie à l'insuline a été posé sur la base des manifestations cliniques, de la positivité des réactions cutanées et, dans 2 cas, des réactions de Prausnitz-Küstner (P.K.). On a obtenu dans 3 cas une désensibilisation. La présence d'anticorps anti-insuline a été révélée par la méthode immunoautoradiographique en employant de l'insuline¹³¹J. Avant la désensibilisation la présence d'anticorps IgG a été enregistrée chez 3 patients tandis que chez 2 on a démontré également des anticorps IgA. Une réaction de P.K. positive a été observée chez des patients dont les sérums contenaient des anticorps IgA. Pendant la désensibilisation on a observé une apparition transitoire de macroglobulines capables de lier l'insuline¹³¹J. Après la désensibilisation on a constaté la persistance de la positivité aux réactions cutanées immédiates à l'insuline de porc et de boeuf. En même temps les réactions retardées et la réaction de P.K. à l'insuline de porc étaient interverties, bien que les mêmes réactions à l'insuline bovine restaient positives.

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Riassunto Cinque pazienti con allergia all'insulina sono stati desensibilizzati con insulina suina secondo il metodo di Urbach e Gotlieb. La diagnosi di allergia all'insulina è stata posta sulla base delle manifestazioni cliniche, della positività delle reazioni cutanee e, in 2 casi, delle reazioni di Prausnitz-Küstner (P.K.). In 3 casi si è ottenuta una desensibilizzazione. La presenza di anticorpi anti-insulina è stata rivelata con il metodo immunoautoradiografico impiegando insulina¹³¹J. Prima della desensibilizzazione la presenza di anticorpi IgG è stata riscontrata in 3 pazienti mentre in 2 sono stati dimostrati anche anticorpi IgA. Una reazione di P.K. positiva è stata osservata in pazienti i cui sieri contenevano anticorpi IgA. Durante la desensibilizzazione si è osservata una comparsa transitoria di macroglobuline capaci di legare l'insulina¹³¹J. Dopo la desensibilizzazione si è riscontrata la persistenza della positività delle risposte cutanee immediate all'insulina suina e bovina. Al tempo stesso le risposte ritardate e la reazione di P.K. all'insulina suina erano invertite, sebbene le stesse reazioni all'insulina bovina rimanessero positive.

     

肥胖型多囊卵巢综合征患者临床及内分泌代谢特征的研究

目的分析总结肥胖型多囊卵巢综合征(PCOS)患者的临床及内分泌代谢特征。方法对象为肥胖型PCOS(A组)70例、非肥胖型(B组)122例以及同期就诊的输卵管因素不孕症患者104例(其中单纯肥胖25例,C组;正常体重79例,D组)作为对照。对上述对象进行临床体征评分,内分泌、代谢指标测定。采用雄激素指数(FAI)评估雄激素增多症,用稳态模型指数(HOMA IR)、胰岛素曲线下面积(IAUC)评估胰岛素敏感性,HOMA-IS、ΔI30/ΔG30评估胰岛β细胞功能。结果(1)A组患者的FAI(3.40±1.84)高于B组(1.75±1.20)和C组(1.65±0.90),P均<0.01。B组黄体生成素(LH)/卵泡刺激素(FSH)比值(2.41±1.13)高于A、C、D组,P均<0.01。(2)192例患者总的胰岛素抵抗发生率为43.23%,A、B组分别为82.86%及20.49%。A组黑棘皮症发生率、空腹胰岛素、IAUC、HOMA IR及甘油三酯水平均高于B组(P均<0.01)。A、B、D组间HOMA IS、ΔI30/ΔG30差异无统计学意义(P>0.05)。(3)人体质量指数、腰臀比与FAI、HOMA-IR均呈正相关(P均<0.01);与LH/FSH比值呈负相关(r=-0.345、-0.260,P<0.01)。结论肥胖型PCOS患者较非肥胖型存在更严重的内分泌及代谢紊乱,胰岛β细胞功能处于代偿期,其远期并发症的防治应受到高度重视。     

瘦素及胰岛素对人类肝细胞癌细胞系细胞瘦素受体mRNA表达的作用

目的研究瘦素及胰岛素对瘦素受体(OB—R)的调节作用。方法以人类肝细胞癌细胞系(HepG2)为实验摸型,采用6孔板培养皿培养HepG2细胞,4个孔作为一个浓度组,通过DNA序列测定及半定量的逆转录-聚合酶链反应等方法,分别观察了0、10^-9、10^-8、10^-7、10^-6mol／L浓度的人类瘦素及胰岛素对HepG2细胞内瘦素受体mRNA表达水平的影响。结果通过RT-PCR及DNA序列测定,我们证明了HepG2细胞含有瘦素长型受体(Ob-Rb)及短型受体(OB-Ra：OB—R219．3);通过半定量RT-PCR,我们检测了Ob-Rb和OB-R219．3的mRNA表达水平。当HepG2细胞与不同浓度的瘦素孵育24h后,10^-7-10^-6mol／L浓度的瘦素明显抑制了OB—Rb的mRNA表达,并在10^-6mol／L浓度时达到最大抑制为43％;同样10^-8-10^-6mol／L浓度的瘦素亦明显抑制了OB-R219．3的mRNA表达,并在10^-6mol／L浓度时达到最大抑制为49％。当HepG2细胞与不同浓度的胰岛素孵育24h后,OB-Rb及OB—R219．3的mRNA表达水平无改变。结论在HepG2细胞内瘦素对OB-Rb及OB—R219．3的mRNA表达有下调作用,而胰岛素对OB-Rb及OB-R219．3的mRNA表达无调节作用,这对与我们了解瘦素抵抗及瘦素的外周功能具有重要意义。     

短期持续皮下胰岛素输注治疗对初诊2型糖尿病疗效的影响因素分析

目的探讨短期持续皮下胰岛素输注(CSII)治疗对初诊2型糖尿病血糖控制的影响因素。方法对138例空腹血糖>11.1mmol/L的初诊2型糖尿病患者进行2周CSII强化治疗,初始胰岛素全日量为0.5U/kg。以指尖空腹血糖(FBG)<6.1mmol/L和餐后2h血糖<8.0mmol/L为血糖控制目标,根据血糖调整胰岛素基础输注量及追加量,比较血糖控制达标组与未达标组患者临床特征、血糖水平和静脉葡萄糖耐量试验时胰岛素曲线下面积(AUC)和Homaβ等。结果经2周CSII治疗,126例(91.3%)患者用泵期间血糖控制达标,12例(8.7%)未达标。与达标组相比,未达标组治疗前FBG较高(16mmol/L±5mmol/L比13mmol/L±4mmol/L)、胰岛素β细胞分泌指数(Homaβ)值较低(17±10比36±25),ΔAUC(治疗后AUC-治疗前AUC)较低,治疗期胰岛素用量较大。结论更严重的高血糖和胰岛β细胞功能低下可能是初诊2型糖尿病患者短期CSII强化治疗血糖控制欠佳的主要原因。     

精氨酸刺激后2分钟胰岛素原所占比例的初步研究

目的探讨和寻找简易的、临床上可行的评估胰岛β细胞功能的方法。方法2001年11月至2002年8月本院住院及门诊患者和本院职工214例,均为居住在上海地区的汉族人,按1999年世界卫生组织(WHO)标准诊断,分为4组,其中正常糖耐量(NGT)组39例、糖耐量受损(IGT)组29例、新诊断2型糖尿病(NT2DM)组43例和原诊断2型糖尿病(PT2DM)组103例。分别检测其空腹及精氨酸刺激后2、4、6min时血糖、真胰岛素(TI)及胰岛素原(PI)水平的变化。结果(1)空腹PI/TI、PI/(TI+PI)在NGT组(19·09%±2·02%和15·31%±1·14%)显著低于IGT组(38·83%±6·80%和24·43%±2·43%,均P<0·05)。(2)精氨酸刺激后TI/血糖分泌曲线由高到低依次为IGT、NGT、NT2DM、PT2DM。PI与PI/血糖在IGT、NT2DM、PT2DM组均于2min时达峰值。(3)PI/TI各组改变与上述TI/血糖改变成镜像现象,并在2min时达低谷值(NGT2·99%±0·27%,IGT6·70%±1·38%,NT2DM10·52%±1·46%,PT2DM11·12%±1·51%)。PI/(TI+PI)变化趋势及差异的显著性与PI/TI相似,此两个参数的2min低谷值由小到大排列顺序为NGT、IGT、NT2DM、PT2DM。结论精氨酸刺激后2min的PI/TI及PI/(TI+PI)值可作为临床评估β细胞功能的一个简易而实用的指标。     

Changes in C-reactive protein predict insulin sensitivity in severely obese individuals after weight loss surgery

The production of inflammatory mediators by abdominal adipose tissue may link obesity and insulin resistance. We determined the influence of systemic levels of interleukin-6 and C-reactive protein on insulin sensitivity after weight loss via Roux-en-Y gastric bypass surgery. Severely obese individuals (n 5 15) were evaluated at baseline and at 6 months after surgery. Insulin sensitivity was determined by frequently sampled intravenous glucose tolerance testing at the same time points. Visceral and subcutaneous adipose tissue volumes were quantified by computed tomography. Interleukin-6 and C-reactive protein were measured by enzyme-linked immunoassay in plasma and in adipose tissue biopsies. Correlation analysis was used to determine associations between insulin sensitivity and other outcome variables. Significance was set at P < 0.05. Plasma interleukin-6 concentrations were significantly correlated to the IL-6 content of subcutaneous adipose tissue (r = 0.71). At 6 months postsurgery, subcutaneous and visceral adipose tissue volumes were significantly reduced (34.7% and 44.1%, respectively) and insulin sensitivity had improved by 160.9%. Significant longitudinal correlations were found between insulin sensitivity and plasma C-reactive protein (r = 20.61), but not plasma interleukin-6 at 6 months. These findings offer insights that link obesity and insulin resistance via the activity of inflammatory mediators. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). Supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases 1R03 DK067167-01A1 (N.G.), the Emory University Research Committee Grant (N.G.), and the National Institutes of Health/National Center for Research Resources General Clinical Research Center Grant M01 RR00039 (N.G., E.L.).     

Significant hyperkalemia after discontinuation of an insulin pump

Patients with diabetes and insulin pumps may need their insulin therapy modified during surgery. Often, this is done with blood glucose as the end point. Changing insulin therapy can also have profound effects on potassium homeostasis in certain patients. This case demonstrates that changes in insulin therapy warrant not only close monitoring of blood glucose, but also of serum potassium. This patient's comorbidities and treatments that could alter potassium homeostasis are also reviewed.