IDDM患者白细胞介素2和白细胞介素6的研究

测定ＩＤＤＭ患者１６例、ＮＩＤＤＭ患者２０例和正常对照组２７例的外周血单个核细胞产生白细胞介素２（ＩＬ－２）和白细胞介素６（ＩＬ－６）的能力。结果：ＩＤＤＭ患者ＩＬ－２水平较正常对照组和ＮＩＤＤＭ患者显著降低（ｐ＜０．００１），ＩＬ－６的水平显著升高（Ｐ＜０．００１）。ＮＩＤＤＭ患者ＩＬ－２和ＩＬ－６与正常对照组差异无显著性。提示ＩＤＤＭ患者ＩＬ－２和ＩＬ－６异常改变导致免疫功能紊乱。     

白细胞介素-5、可溶性白细胞介素-2受体及一氧化氮与哮喘发病的关系

目的探讨白细胞介素-5(IL-5)、可溶性白细胞介素-2受体(sIL-2R)、一氧化氮(N())及嗜酸性粒细胞(EOS)在哮喘发病中的意义。方法对治疗前后的急性发作期、稳定期哮喘组及对照组血清II-5、sIL-2R和NO水平及EOS计数进行了研究。结果哮喘急性发作组血清IL-5、sIL-2R、NO及EOS水平均明显高于哮喘缓解期组与对照组。哮喘发作期IL-5与EOS呈显著正相关。哮喘急性发作期组治疗后sIL-2R及NO水平较治疗前显著降低,IL-5与EOS水平下降但无统计学意义。结论血清IL-5、sIL-2R、NO及EOS水平升高,与哮喘发作密切相关。     

浆细胞病患者血清可溶性白细胞介素2受体测定

浆细胞病患者血清可溶性白细胞介素２受体测定王加林，侯健，王亚伟，夏志学，方卫华浆细胞病系好发于老年人的浆细胞恶性增生性疾病，其免疫机能异常既是本病的致病因素，同时又是本病的严重后果。我们用双抗体夹心酶联免疫吸附法（ＥＬＩＳＡ），对３１例浆细胞病患者血...     

老年糖尿病病人血清可溶性白细胞介素Ⅱ受体检测及其意义

老年糖尿病病人血清可溶性白细胞介素Ⅱ受体检测及其意义王秀清，李静波，许丽艳，何娜（白求恩医科大学应用基础医学研究所，长春１３００２１）傅军，于晓丽，郑如（白求恩医科大学第一临床学院）王宪富（白求恩医科大学第三临床学院）有关糖尿病特别是Ⅱ型糖尿病与免疫...     

胃癌患者血清可溶性白细胞介素—2受体初步研究

应用双抗体夹心ＥＬＩＳＡ法对３０例胃癌患者血清ＳＩＬ－２Ｒ水平进行测定，结果表明，胃癌患者血清ＳＩＬ－２Ｒ水平明显高于正常对照（Ｐ＜０．０１）及慢性良性胃病患者（Ｐ＜０．０５）；Ⅲ－Ⅳ期患者血清ＳＩＬ－２Ｒ水平显著高于Ｉ－ＩＩ期患者（Ｐ＜０．０５）；低度分化者较中度分化者ＳＩＬ－２Ｒ水平明显升高（Ｐ＜０．０１）；贲门癌患者ＳＩＬ－２Ｒ水平较胃窦（体）癌者高，但未达到统计学差别（Ｐ＞０．０５）；胃癌     

衰老与白细胞介素2及其受体关系的研究进展

在衰老与免疫系统关系的研究中,发现衰老与机体的白细胞介素2(IL-2)产生和白细胞介素2受体(IL-2R)表达水平有较为密切关系。本文对衰老与白细胞介素2及其受体关系的研究进展作一综述。     

胃癌患者血清可溶性白细胞介素－2受体初步研究

应用双抗体夹心ＥＬＩＳＡ法对３０例胃癌患者血清ｓＩＬ－２Ｒ水平进行测定。结果表明，胃癌患者血清ｓＩＬ－２Ｒ水平明显高于正常对照（Ｐ＜０．０１）及慢性良性胃病患者（Ｐ＜０．０５）；Ⅲ－Ⅳ期患者血清ｓＩＬ－２Ｒ水平显著高于Ⅰ－Ⅱ期患者（Ｐ＜０．０５）；低度分化者较中度分化者ｓＩＬ－２Ｒ水平明显升高（Ｐ＜００１）；贲门癌患者ｓＩＬ－２Ｒ水平较胃窦（体）癌者高，但未达到统计学差别（Ｐ＞０．０５）；胃癌根治术后一周血清ｓＩＬ－２Ｒ水平较术前升高（Ｐ＜０．０１），术后二周血清ｓＩＬ－２Ｒ较术前明显降低（Ｐ＜０．０１），与正常人相比无明显差异（Ｐ＞００５）。结果提示血清ｓＩＬ－２Ｒ测定可作为胃癌患者病情判断、观察疗效及估价预后新的生物学指标。     

Autoantibodies associated with presymptomatic insulin-dependent diabetes mellitus in women

Presymptomatic autoantibody markers of insulin-dependent (Type 1) diabetes mellitus (IDDM) are less well characterized in adults than in children. We quantitated anti-GAD, anti-ICA512 and ICA by titration to endpoint and compared frequencies and levels in 139 Finnish women from whom 390 serum samples had been archived during antecedent pregnancies for 10 years before and up to 1 year after diagnosis of diabetes. Also, we compared the autoantibody status in adults with IDDM with that of children with newly diagnosed IDDM. Of the 35 women seropositive for 1 or more autoantibodies, 77 % developed IDDM, 11 % non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), 9 % gestational diabetes mellitus requiring insulin (GDM-ins) and 3 % GDM controlled by diet. The frequency of antibodies during the 10-year presymptomatic period was 83 % for anti-glutamic acid decarboxylase (GAD), 52 % for anti-ICA512 and 41 % for islet cell antibodies (ICA) for those who developed IDDM, 25 %, 17 %, and 0 % for NIDDM, 12 %, 4 %, and 8 % for GDM-ins and 1 %, 0 %, and 1 % for GDM-diet. Anti-GAD was found most consistently in early samples; 13 of 15 with a single autoantibody at their first test had anti-GAD. Among those who developed IDDM, the frequency of anti-GAD was constant, anti-ICA512 increased threefold, and ICA increased slightly before diagnosis. Levels of the autoantibodies varied between subjects, but were relatively stable in individual subjects. Comparison of tests on the women, and children after diagnosis of IDDM, showed the frequencies and levels to be the same for anti-GAD but lower for anti-ICA512 and ICA in adults. Our observations show in women the long latency of seropositivity before overt IDDM, the predominance of anti-GAD among these three serological markers, and the presence of these markers in NIDDM presumably representing a NIDDM phase of autoimmune insulitis. © 1997 by John Wiley & Sons, Ltd.     

Prevention of insulin-dependent diabetes mellitus 1998

Recent advances in the understanding of the pathogenesis of insulin-dependent diabetes mellitus (IDDM) have led to the first trials of disease prevention in susceptible individuals. Two main trials (nicotinamide and insulin) are now running but first results will not be available before the turn of the century. Pilot trials using different approaches, most of them based on the induction of immunotolerance, are also under way and should offer new insight for establishing larger multicentre studies including attempts aimed at primary prevention by removal of diabetogenic components in cow’s milk. The field is moving fast and it is expected that intervention for IDDM prevention will be offered to an increasing number of individuals found at risk of developing the disease. © 1998 John Wiley & Sons, Ltd.     

Prevalence of insulin-dependent diabetes mellitus in Asian children

A survey was conducted in 1984-85, within Leicester City boundaries, which contains 64,535 children below the age of 15 years (20,267 Asian and 44,268 White Caucasian) to ascertain the prevalence of insulin-dependent diabetes mellitus (IDDM) using a central register maintained for the changeover to U-100 insulin, diabetic health visitor index cards, hospital admissions of diabetic children, and individual registers maintained by us. Overall prevalence per thousand for children aged 0-15 years was 0.54 for Asian and 0.99 for White Caucasians; for ages 10-15 years they were 0.97 and 1.87, and for ages 0-9 years, 0.31 and 0.38, respectively. This was not statistically different at the 5% level. Ours is the first population based study of its kind in Asian children, and challenges the view that there is a large difference in the prevalence of IDDM between Asians and White Caucasians. A wider analysis of this observation incorporating a large population base is suggested.     

Tumour-induced hypoglycaemia in a patient with insulin-dependent diabetes mellitus

We report on a case of malignant insulinoma occurring in a patient with genuine insulin-dependent diabetes mellitus (IDDM). A review of cases concerning patients with diabetes mellitus and insulinomas is presented, and reveals only patients with non-insulin-dependent diabetes mellitus (NIDDM). Our case appears to be the first in showing the combination of IDDM and a functioning malignant insulinoma.     

Imbalance of the interleukin 2 system in children with IDDM

Summary The IL-2 system which involves IL-2 production, IL-2 receptor expression, and response to IL-2, is associated with autoimmune phenomena. Immunological abnormalities including autoimmune phenomena are believed to contribute to the pathogenesis of IDDM. In this study, the production of IL-2, the responses to IL-2 and IL-2 receptor expression by peripheral blood T lymphocytes were compared in IDDM and normal non-diabetic children. The percentage of IL-2 receptor-positive circulating T cells was significantly increased in diabetic children, although IL-2 receptor expression induced by con A stimulation did not differ in the diabetic and control children. IL-2 production was significantly decreased in diabetic children compared with the control children. The response of stimulated T cells to IL-2 did not differ in IDDM and control children. In IDDM, IL-2 production by CD4-positive T lymphocytes within the IL-2 system is thought to be selectively defective. On the other hand, IL-4, which is also produced by CD4-positive T lymphocytes, was increased. Since IL-4 did not suppress IL-2 production, it would seem that the IL-2 producing subset in CD4⁺HLA-DR⁺ T cells is decreased in IDDM. These results suggest that in recent onset IDDM, IL-2 receptor-positive circulating T cells require an IL-2 supply.[Diabetologia (1994) 37: 476–482] Received: 13 August 1993 and in revised form: 23 November 1993     

白细胞介素-6受体基因单核苷酸多态性及单体型与2型糖尿病的相关性研究

目的 探讨白细胞介素-6受体(IL-6R)基因单核苷酸多态性(SNP)及单体型与2型糖尿病的相关性.方法 选择入住本院的88例2型糖尿病(T2DM)患者为2型糖尿病组,以同期体检并糖耐量正常的98例健康自愿者为对照组,采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)方法对IL-6R基因的2个SNP位点予以基因型检测.采用聚类分析方法分析基因多态性特征.结果 2型糖尿病组D358A基因型中A等位基因频率较对照组高,C等位基因频率较对照组降低,差异有统计学意义(P＜0.05).2型糖尿病组-183(G→A)基因型频率与等位基因频率和对照组比较,差异均无统计学意义(P＞0.05).A2-G单体型在两组中最为常见,其频率分布为0.391、0.288(P =0.053).在4种单体型中两组仅C-A1单体型的频率差异有统计学意义,分别为0.103、0.281 (P =0.001).结论 IL-6R基因第9外显子D358A(rs8192284)是种有价值的遗传性标志,C等位基因对2型糖尿病具有保护作用,携带C-A2单体型的人群较易患2型糖尿病.     

Reduced transcapillary fluid absorption from skeletal muscle and skin during hypovolaemia in insulin-dependent diabetes mellitus

OBJECTIVES: Diabetes mellitus is associated with a high cardiovascular morbidity which has been linked to disturbances in microvascular function. This study was designed to examine the transcapillary fluid absorption during experimental hypovolaemia in type 1 diabetes. SUBJECTS: Twelve males with type 1 diabetes (age 25 +/- 3 years, duration 8 +/- 1 years) with no clinical microangiopathy and 12 healthy males (22 +/- 2 years). INTERVENTIONS: As a model for hypovolaemic circulatory stress, lower body negative pressure (LBNP: 15, 30 and 60 cmH2O) was used. Transcapillary fluid absorption from tissue to blood in the upper arm, as well as forearm blood flow, was measured by volumetric technique. RESULTS: Resting forearm blood flow, heart rate and blood pressure were similar in diabetic patients and controls. Basal plasma noradrenaline was reduced in the diabetics compared with controls (0.75 +/- 0.06 vs. 1.09 +/- 0.10 pmol L-1, P < 0.05), but the increase in plasma noradrenaline in response to LBNP was similar in the two groups. The haemodynamic responses to LBNP in the two groups were equal, showing a reduction of pulse pressure, an increase in heart rate and in peripheral resistance with a concomitant blood flow reduction. The transcapillary fluid absorption (mL 100 mL-1 min-1) was significantly reduced in the diabetic patients: LBNP 15 cmH2O, 0.024 +/- 0.004 vs. 0.036 +/- 0. 002; 30 cmH2O, 0.041 +/- 0.003 vs. 0.056 +/- 0.005; and 60 cmH2O, 0. 057 +/- 0.007 vs. 0.091 +/- 0.008 (diabetic patients vs. controls, P < 0.001). CONCLUSIONS: The transcapillary fluid absorption from tissue to blood during hypovolaemic circulatory stress in type 1 diabetic patients is reduced by one-third compared with controls, which indicates impaired plasma volume regulation. This basic mechanism for plasma volume control is affected before clinical microcirculatory complications are found and could be one of the causes of the increased cardiovascular morbidity and mortality in IDDM.     

Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: a meta-analysis

While the benefits of intensified insulin treatment in insulin-dependent (Type 1) diabetes mellitus (IDDM) are well recognized, the risks have not been comprehensively characterized. We examined the risk of severe hypoglycaemia, ketoacidosis, and death in a meta-analysis of randomized controlled trials. The MEDLINE database, reference lists, and specialist journals were searched electronically or by hand to identify relevant studies with at least 6 months of follow-up and the monitoring of glycaemia by glycosylated haemoglobin measurements. Logistic regression was used for calculation of combined odds ratios and 95 % confidence intervals (95 % CI). The influence of covariates was examined by including covariate-by-treatment interaction terms. Methodological study quality was assessed and sensitivity analyses were performed. Fourteen trials were identified. These contributed 16 comparisons with 1028 patients allocated to intensified and 1039 allocated to conventional treatment. A total of 846 patients suffered at least one episode of severe hypoglycaemia, 175 patients experienced ketoacidosis and 26 patients died. The combined odds ratio (95 % CI) for hypoglycaemia was 2.99 (2.45–3.64), for ketoacidosis 1.74 (1.27–2.38) and for death from all causes 1.40 (0.65–3.01). The risk of severe hypoglycaemia was determined by the degree of normalization of glycaemia achieved (p = 0.005 for interaction term), with the results from the Diabetes Control and Complications Trial (DCCT) in line with the other trials. Ketoacidosis risk depended on the type of intensified treatment used. Odds ratios (95 % CI) were 7.20 (2.95–17.58) for exclusive use of pumps, 1.13 (0.15–8.35) for multiple daily injections and 1.28 (0.90–1.83) for trials offering a choice between the two (p = 0.004 for interaction). Mortality was significantly (p = 0.007) increased for causes potentially associated with acute complications (7 vs 0 deaths, 5 deaths attributed to ketoacidosis, and 2 sudden deaths), and non-significantly (p = 0.16) decreased for macrovascular causes (3 vs 8 deaths). We conclude that there is a substantial risk of severe adverse effects associated with intensified insulin treatment. Mortality from acute metabolic causes is increased; however, this is largely counterbalanced by a reduction in cardiovascular mortality. The excess of severe hypoglycemia in the DCCT is not exceptional. Multiple daily injection schemes may be safer than treatment with insulin pumps. © 1997 John Wiley & Sons, Ltd.     

Long QT syndrome with insulin-dependent diabetes mellitus: contiguous gene syndrome on chromosome 11p

Abstract. Long QT syndrome (Romano-Ward syndrome) and insulin-dependent diabetes mellitus (IDDM) have been documented as being linked with gene(s) on chromosome 11p although concurrence of the two disorders has not been reported. Our case is a 13-year-old boy with Romano-Ward syndrome accompanied by IDDM. The long QT syndrome seemed to be transmitted in an autosomal-dominant mode because the Q-T intervals of his father and paternal grandfather were longer than normal. There was no family member with an abnormally high level of blood glucose except the patient. The human leucocyte antigen (HLA) haplotypes of the patient and the father were DR4/DR9 and DR2/DR9, respectively. This study suggests that in our patient IDDM, as well as Romano-Ward syndrome, is linked with chromosome 11p in the presence of HLA-DR4. The results support the previous study that chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility.     

The natural history of insulin-dependent diabetes mellitus in Denmark: 1. Long-term survival with and without late diabetic complications

All 906 patients with insulin-dependent diabetes mellitus (IDDM) diagnosed before the age of 31 years, prior to 1943, and admitted to the Steno Memorial Hospital were followed until death or until 1 January 1984. In an attempt to identify factors of prognostic importance, we compared patients dying within 35 years of the onset of diabetes with patients surviving for 40 years or more. Three hundred and seventy-seven patients survived for 40 years or more; of these 224 were still alive and invited to a re-examination, in which 184 participated. After 40 years of diabetes, the most frequent complications were impaired vision (due to diabetic retinopathy) and persistent proteinuria. However, 53% had no major complications despite 40 years with IDDM. The 184 re-examined patients (median age 60 years, median diabetes duration 47 years) were all genuine IDDM patients, as defined by stimulated C-peptide levels. Proliferative retinopathy or visual impairment was found in 56% of the 184 patients, abnormal ECG or amputations in 26%, and elevated urinary albumin excretion rate (AER) greater than or equal to 30 mg/24 h) in 45%. Twenty-five per cent had none of these complications. Proliferative retinopathy was associated with elevated AER and raised systolic blood pressure, macroangiopathy with the use of antihypertensive drugs, and proteinuria with low age at diagnosis, large increase in systolic blood pressure, smoking, and insulin-binding antibodies. Sex, age and diabetes duration were not associated with any of these three late diabetic complications.