IDDM与白细胞介素2／白细胞介素2受体系统的关系

探讨２０例胰岛素依赖型糖尿病（ＩＤＤＭ）患者外周血单个核细胞（ＰＢＭＮＣ）经ＴＰＡ／Ａ２３１８７刺激培养４８小时后的白细胞介素２（ＩＬ－２）产生水平，以及培养前后的白细胞介素２受体（ＩＬ－２Ｒ）表达。结果表明：１．ＩＤＤＭ病人体外ＩＬ－２产生较正常对照组明显下降，且与病程长短及血糖水平无关。２．刺激培养前的ＩＤＤＭ病人ＰＢＭＮＣ表达ＩＬ－２Ｒ：①病程小于１年的５例病人表达ＩＬ－２Ｒ较对照组明显增高     

扩张型心肌病白细胞介素2受体的初步研究

检测２０例扩张型心肌病（ＤＣＭ）及２０例正常人（ＮＣ）的血清可溶性白细胞介素２受体（ＳＩＬ－２Ｒ）及外周血单个核细胞膜白细胞介素２受体（ＩＬ－２Ｒ）的表达。结果发现，ＤＣＭ患者ＳＩＬ－２Ｒ明显高于ＮＣ组（Ｐ＜０．００１），而膜ＩＬ－２Ｒ表达低于ＮＣ组（Ｐ＜０．０１），提示ＩＬ－２Ｒ在ＤＣＭ发病中可能有一定意义。     

老年冠心病患者血清白细胞介素—6和白细胞介素—8水平变化及其？…

为探讨白细胞介素－６（ＩＬ－６）和白细胞介素－８（ＩＬ－８）与冠心病（ＣＨＤ）的相互关系及临床意义，采用双抗体夹心法（ＥＬＩＳＡ）检测了５５例老年ＣＨＤ患者血清ＩＬ－６，ＩＬ－８的水平变化并与２５例临床老年人对照，结果显示ＣＨＤ患者血清ＩＬ－６和ＩＬ－８水平明显高于对照组（Ｐ〈０．０５），且ＩＬ－６和ＩＬ－８之间呈正相关（ｒ＝０．４２３，Ｐ〈０．００１），提示ＩＬ－６和ＩＬ－８的水平变化与ＣＨＤ密     

扩张型心肌病及冠心病血浆白细胞介素6的研究

采用放射免疫竞争结合法测定４０例扩张型心肌病（ＤＣＭ）及２５例冠心病（ＣＨＤ）患者的血浆白细胞介素６（ＩＬ－６）水平，并与对照组（ＮＣ）１３例相比较，结果表明ＤＣＭ组血浆ＩＬ－６水平显著高于ＣＨＤ组及ＮＣ组（Ｐ＜０．０１），而ＣＨＤ组与ＮＣ组相比无显著差异（Ｐ＞０．０５）。提示ＩＬ－６在ＤＣＭ发病中是主要因子，其作用机理为：一方面通过增强体液及细胞免疫增强抗病毒作用；另一方面通过加重抑制性Ｔ细胞／细胞溶解性Ｔ淋巴细胞（Ｔｓ／ＣＴＬ）功能紊乱，介导自身免疫的发生。在其他方面，ＩＬ－６作为其他细胞因子（如白细胞介素Ｉ）的负反馈调节因子，减轻心肌的炎症反应，达到保护心肌的作用，从而在扩张型心肌病的发病中起到双向调节作用。     

高血压患者脂质过氧化物及白细胞介素Ⅱ的相关性

目的探讨脂质过氧化物（ＭＤＡ）及白细胞介素Ⅱ（ＩＬ－２）。方法用硫代巴比妥酸微量法及双抗夹心法测定４６例高血压患者及２０例健康的ＭＤＡ和ＩＬ－２。结果高血压患者ＭＤＡ明显高于健康对照组（Ｐ＜０．０５）而高血压患者ＩＬ－２明显低于对照组（ｒ＝－０．７３２，Ｐ＜０．０５）。结论高血压患者存在ＭＤＡ和ＩＬ－２异常，ＩＬ－２与ＭＤＡ有内在联系，氧自由基（ＯＦＲ）损伤淋巴细胞可能是导致ＩＬ－２异常的原因之一。     

SLE患者血清中白细胞介素-2受体和睾酮水平的变化

选择５９例系统性红斑狼疮（ＳＬＥ）患者和２０例正常人,检测白细胞介素－２受体（ｓＩＬ－２Ｒ）和睾酮（Ｔｃ）水平。用疾病活动评分（ＳＬＡＭ）判断疾病活动性,并对ｓＩＬ－２Ｒ和Ｔｃ水平的变化及两者回的相关性进行分析。结果ＳＬＥ患者血清ｓＩＬ－２Ｒ水平显著高于正常人（Ｐ〈０．００１）,Ｔｅ显著低于正常人（Ｐ〈０．００１）,ＳＬＥ活动期ｓＩＬ－２Ｒ水平与ＳＬＡＭ指数显著高于非活动期（Ｐ〈０．０１）,Ｔｅ显     

心律失常患者血清可溶性白细胞介素－2受体的变化及意义初探

应用酶标双抗体夹心法（ＥＬＩＳＡ）测定３０例心律失常患者（其中心房颤动１２例、室性早搏９例、房性早搏９例）血清可溶性白细胞介素－２受体（ＳＩＬ－２Ｒ）的水平。以３２例不伴心律失常的心脏病患者作对照，并与３０例正常人作比较。三组血清ＳＩＬ－２Ｒ水平分别为３７０．１±１８１．８，１８４．５±９６．５，７９．１±２７．４ｕ／ｍｌ，心律失常组高于对照组和正常组（Ｐ均＜０．００１）；对照组ＳＩＬ－２Ｒ水平亦高于正常组（Ｐ＜０．００１）；不同类型心律失常患者的血清ＳＩＬ－２Ｒ水平比较差异无显著性（Ｐ＞０．０５）。提示心律失常患者可能存在免疫功能紊乱；ＳＩＬ－２Ｒ可作为衡量心律失常患者的细胞免疫活性的一个指标。     

病毒性心肌炎可溶性白细胞介素2受体、自然杀伤细胞活性及T细胞亚群的检测

应用单克隆与多克隆双抗体夹心法检测３６例病毒性心肌炎（ＶＭＣ）及２４例正常人（ＮＣ）的血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ），同时测定外周血自然杀伤细胞（ＮＫＣ）活性和Ｔ淋巴细胞亚群。结果显示ＶＭＣ患者ｓＩＬ－２Ｒ明显高于ＮＣ组（Ｐ＜０．００１）．而ＮＫＣ活性明显低于ＮＣ组（Ｐ＜０．０１），Ｔ细胞亚群与ＮＣ组比较，急性ＶＭＣ患者总Ｔ细胞（ＣＤ３），辅助性Ｔ细胞（ＣＤ４）和抑制性Ｔ细胞（ＣＤ８）均减少，ＣＤ４／ＣＤ８比值显著降低（Ｐ＜０．０５．０．０１），以细胞免疫功能低下为明显；而ＶＭＣ后遗症期患者ＣＤ３、ＣＤ４与ＮＣ组无差异（Ｐ＞０．０５），ＣＤ８显著降低（Ｐ＜０．０５），ＣＤ４／ＣＤ８比值显著高于ＮＣ组（Ｐ＜０．０５），以细胞免疫调节失衡为主。上述结果提示细胞免疫功能低下及免疫功能失调为ＶＭＣ发病及影响预后的重要因素。     

老年多发性骨髓瘤患者血清白细胞介素—2的检测及临床意义

目的检测老年多发性骨髓瘤（ＭＭ）患者血清白细胞介素－２（ＩＬ－２）含量，分析其临床意义。方法用固相放射免疫分析（ＲＩＡ）法检测４４例初诊老年ＭＭ患者、２０例健康老年人和４０例健康青中年人血清ＩＬ－２含量，随访患者３年的存活状况。结果ＭＭ患者血清ＩＬ－２为８．１１±２．５４μｇ／Ｌ，显著高于老年健康对照组的２．６８±０．６１μｇ／Ｌ（Ｐ＜０．０１）。血清ＩＬ－２≥５μｇ／Ｌ的患者３年生存率显著提高。血清ＩＬ－２与血清β２微球蛋白（β２－ＭＧ）有关，血清ＩＬ－２≥５μｇ／Ｌ的患者，β２－ＭＧ皆＜６ｍｇ／Ｌ。结论血清ＩＬ－２的检测可作为估计ＭＭ预后的一项指标。     

心血管疾病中可溶性白细胞介素2受体的检测及应用

应用酶标双抗体夹心法测定了２０例扩张型心肌病（ＤＣＭ）、１０例高血压病（ＥＨＴ）、１５例冠心病（ＣＨＤ）及１８例肥厚型心肌病（ＨＣＭ）外周血清可溶性白细胞介素２受体（ＳＩＬ－２Ｒ）的浓度，并与２０例正常人（ＮＣ）比较，结果表明ＤＣＭ及ＥＨＴ组ＳＩＬ－２Ｒ明显高于ＣＨＤ、ＨＣＭ及ＮＣ组（Ｐ＜０００１），而ＨＣＭ、ＣＨＤ及ＮＣ组之间两两比较无统计学差异（Ｐ＞０．０５），表明ＤＣＭ及ＥＨＴ患者ＳＩＬ－２Ｒ异常紊乱，ＳＩＬ－２Ｒ的检测可作为衡量某些心血管疾病细胞免疫活性的指标。     

Ⅰ型糖尿病患者外周血NK细胞活性降低

以改良铬（５１Ｃｒ）释放法检测３４例Ⅱ型糖尿病（ＮＩＤＤＭ）、２３例Ｉ型糖尿病（ＩＤＤＭ）和２８例正常人外周血ＮＫ细胞对Ｋ５６２靶细胞的杀伤活性。结果显示：①ＩＤＤＭ组患者ＮＫ细胞活性显著低于ＮＩＤＤＭ组及正常对照组，经正规治疗血糖控制以后，ＮＫ细胞活性恢复正常。②ＮＩＤＤＭ组患者血ＮＫ细胞活性在血糖控制前后无显著变化，与正常对照组比较亦无统计学差异。提示ＩＤＤＭ与机体免疫异常密切关联。     

IDDM自身抗体与胰岛功能的研究

本文测定了36例新诊断、未使用过外源胰岛素的IDDM患者的血清胰岛细胞抗体(ICA)、血清胰岛素自身抗体(IAA)及血清C肽和胰岛素水平,并以72例新诊断的NIDDM和36例正常人作为对照。研究表明:自身免疫在IDDM病因中占有重要地位;临床发病时ICA、IAA阳性可以作为IDDM自身免疫的标志,但不能反映胰岛β细胞功能损害的程度。     

Phosphodiesterase activity in human subcutaneous adipose tissue in insulin- and noninsulin-dependent diabetes mellitus

The influence of diabetes mellitus on phosphodiesterase (PDE) activity in human sc adipose tissue was investigated in 8 patients with insulin-dependent (IDDM) and 9 with noninsulin-dependent (NIDDM) diabetes mellitus. The results were compared with data from 10 healthy normal weight subjects. The apparent maximal PDE activity (Vmax) of the low Km form of PDE was 60% lower (P less than 0.01) in untreated IDDM and NIDDM than in the control state. After treatment of IDDM and NIDDM, the Vmax of the low Km PDE was normalized. In untreated IDDM and NIDDM, the Vmax of the low Km PDE was correlated to the cAMP level (r = 0.8). This correlation was not observed after antidiabetic treatment or in the control state. The apparent Vmax values of the high Km form of PDE were similar in the diabetic states and in control subjects. The results suggest that the low Km PDE is inhibited in untreated IDDM and NIDDM. In these conditions, PDE may be one factor responsible for regulation of the cAMP level.     

Glucose tolerance and insulin response in parents of patients with insulin-dependent and juvenile-onset non-insulin-dependent diabetes mellitus.

Glucose tolerance and insulin response were examined using a 100 g oral glucose tolerance test (OGTT) in 108 parents of 23 patients with insulin-dependent (IDDM) and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose age of onset of diabetes was less than 35 years. Thirty-two age-matched healthy volunteers without a family history of diabetes were also examined as a control group. Diabetes and impaired glucose tolerance (IGT) were significantly more frequent in parents of NIDDM (diabetes 34%, IGT 27%) than in parents of IDDM (diabetes 7%, IGT 13%) (P less than 0.001). At least one parent had diabetes or IGT in 30% of IDDM and 84% of NIDDM patients (P less than 0.001), and both parents had diabetes or IGT in 9% of IDDM and 39% of NIDDM patients (P less than 0.02). Even in cases with 'normal' glucose tolerance, the mean plasma glucose was higher in parents of NIDDM than in control subjects, suggesting a high prevalence of abnormal glucose tolerance including the marginal degree of abnormality in the families of NIDDM. The early phase insulin response was decreased more among parents of NIDDM with the greater impairment of glucose tolerance. However, among those with 'normal' glucose tolerance, early phase insulin response did not differ between parents of IDDM and NIDDM, and control subjects. The results confirmed a stronger familial background in NIDDM patients of younger onset than in IDDM. The different patterns of glucose tolerance among two parents of young-onset NIDDM patients suggest heterogeneity of the mode of inheritance of NIDDM among families.     

Epidemiological and immunogenetic analysis of tuberculosis and diabetes mellitus association

The prevalence of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) among adults in two Moscow okrugs was studied. It was 0.218 and 1.678%, respectively, the latter form being encountered 7.7 times more frequently. Patients with pulmonary tuberculosis followed at tuberculosis control dispensaries (n = 69,012) were found to have diabetes mellitus in 236 cases (120 with IDDM and 116 with NIDDM). The prevalence of IDDM among the tuberculosis control dispensary patients was 1.7%, which was 8 times greater than that in the general population. That of NIDDM was 1.68%, which did not significantly differ from that in the population. Epidemiological analysis showed that there was a highly significant association of tuberculosis with diabetes mellitus in the population. The risk for IDDM was 3.6% in patients and exceeded that in the population while the risk for NIDDM in the population was the same as that in the population. Analyzing the distribution of immunogenetic HLA-1 and HLA-2 markers showed that patients with tuberculosis concurrent with IDDM were intermediate between a group of patients with isolated tuberculosis and isolated IDDM.     

Age of onset and type of Japanese younger diabetics in Tokyo

The age of onset of diabetes and the type of diabetes were examined in 1408 Japanese patients who were initially diagnosed as having diabetes under the age of 30 and were registered in our Diabetes Center between 1980 and 1989. Of the 1408 patients, 538 (38.2%) had insulin-dependent diabetes mellitus (IDDM) (male/female ratio of 2:3), and 870 (61.8%) had non-insulin-dependent diabetes mellitus (NIDDM) (male/female ratio of 5:4). There were significant differences of the sex ratio in both IDDM and NIDDM. The age at which the numbers in both the IDDM and NIDDM groups were almost equal was 13–14 (26 for IDDM and 23 for NIDDM at 13; 28 for IDDM and 30 for NIDDM at 14). A total of 58% of IDDM patients (22% of all patients) and only 6% of NIDDM patients (4% of all patients) were diagnosed under the age of 14 (P < 0.01). Of the patients with IDDM, 42% (16% of all patients) were diagnosed over the age of 14, as were 94% of NIDDM (58% of all patients). The percentage of NIDDM cases increased even more over the age of 28, and no NIDDM patients developed diabetes under the age of 9.     

血清胰岛细胞抗体的测定及临床意义

作者采用Ｏ型血人新鲜胰腺冰冻切片作抗原，建立了血清胰岛细胞胞浆抗体（ＩＣＡ）的间接免疫荧光测定方法。对１５７例糖尿病患者（其中ＩＤＤＭ８２例、ＮＩＤＤＭ７５例）和８４例正常人进行了血清ＩＣＡ检测。结果，ＩＤＤＭ组、ＮＩＤＤＭ组和对照组的ＩＣＡ阳性率分别为３１．５％、１３．３％和１．１％，３组间差异有非常显著性（Ｐ＜０．００５）。ＩＤＤＭ组中，病程６个月以内者ＩＣＡ阳性率为４１．７％，病程超过６个月者为２２．６％，差异无显著性。１０例ＩＣＡ阳性的ＮＩＤＤＭ病人中，４例为口服降糖药继发失效者。提示ＩＣＡ是ＩＤＤＭ的自身免疫血清学标志，对糖尿病的病因学诊断分型及判断ＮＩＤＤＭ口服降糖药继发失效有重要意义。     

Effects of Insulin on Body Composition in Patients with Insulin-dependent and Non-insulin-dependent Diabetes

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (∼0.6 units kg⁻¹ day⁻¹). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA_1c was greater in IDDM (5.2 ± 0.7 %) than in NIDDM (2.0 ± 0.4 %, p < 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 ± 1.2 vs 3.77 ± 0.5 kg, p < 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 ± 9.3 %) and fat mass in NIDDM (59.9 ± 8.4 %). The increase in lean mass was greater in IDDM than NIDDM (5.6 ± 1.1 vs 1.4 ± 0.3 kg, p < 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 ± 0.8 vs 2.4 ± 0.5 kg, p = ns) and was predominantly an increase in trunk fat (IDDM: 2.3 ± 0.6 kg, NIDDM: 2.0 ± 0.4 kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 ± 0.05 vs 1.09 ± 0.09, p < 0.01) and then increased in IDDM by 0.32 ± 0.15 (p = 0.07) and in NIDDM by 0.22 ± 0.06 (p < 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.     

Adverse effects of obesity on lipid and lipoprotein levels in insulin-dependent and non-insulin-dependent diabetes

We studied the association of obesity with lipid and lipoprotein concentrations in 92 patients (49 men, 43 women) with insulin-dependent diabetes (IDDM), in 305 patients (152 men, 153 women) with non-insulin-dependent diabetes (NIDDM), and in 122 nondiabetic control subjects (65 men, 57 women). Obesity (body mass index, BMI) was associated with abnormal lipid and lipoprotein levels only in the presence of diabetes, and lipid and lipoprotein changes were substantially more abnormal in patients with NIDDM than in patients with IDDM. In men and women with NIDDM, obesity was associated with low high-density lipoprotein (HDL) and HDL2 cholesterol and high total, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) triglyceride concentrations. In men with IDDM, obesity was related only to low HDL and HDL2 cholesterol and in women with IDDM to low HDL3 cholesterol. BMI and diabetes status had a statistically significant interaction (analysis of variance) with respect to HDL and HDL2 cholesterol and total and VLDL triglycerides, indicating that the effects of obesity on lipids and lipoproteins were more severe in patients with diabetes than in nondiabetic subjects. In conclusion, obesity and diabetes status have an unfavorable interaction that results in multiple pathologic lipid and lipoprotein changes, particularly in NIDDM.     

Urinary C-peptide as an index of unstable glycemic control in insulin-dependent diabetes mellitus (IDDM)

In order to investigate whether urinary C-peptide (UCP) excretion can be a useful index of insulin-dependent diabetes mellitus (IDDM) with unstable glycemic control, UCP was measured in nine IDDM patients with unstable glycemic control, nine IDDM patients with stable glycemic control, and 12 non-insulin-dependent diabetic (NIDDM) patients treated with insulin. The UCPs in overnight urine (U1) and fasting single void urine (U2) in IDDM patients with unstable glycemic control were significantly lower than those in IDDM patients with stable glycemic control (U1: 0.03 +/- 0.03 vs 0.24 +/- 0.20 nmol/mmol-Creatinine, U2: 0.02 +/- 0.01 vs 0.20 +/- 0.20 nmol/mmol-Cr, mean +/- SD, both P less than 0.01). The UCPs in U1 and U2 in both groups of IDDM were significantly lower than those in NIDDM (U1: 0.97 +/- 0.52, U2: 0.73 +/- 0.41 nmol/mmol-Cr, both P less than 0.01). The UCPs in U1 and U2 significantly correlated with incremental C-peptide response to intravenous glucagon injection and with glycemic stability assessed by the standard deviation of 10 previous fasting plasma glucose levels. These results suggest that UCP reflects their residual insulin secretory capacity and that UCP can be a useful index which distinguishes patients with unstable IDDM from those with stable diabetes mellitus.