Identification of insulin-dependent diabetes mellitus before the onset of clinical symptoms.
Identification of insulin-dependent diabetes mellitus before the onset of clinical symptoms.
复制标题
在临床症状出现之前识别胰岛素依赖型糖尿病。
DOI：
10.1016/s0022-3476(88)80078-7
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Maclaren,NK
中科院分区：
文献类型：
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作者：
Riley,WJ;Winter,WE;Maclaren,NK
预防医学是建立在对疾病的发病机制和自然史的了解之上的。对胰岛素依赖型糖尿病的疾病易感性进行筛查，可以在β细胞出现明显程度的损伤之前识别出“有风险”的个体。如果有有效和安全的预防性治疗和适当的疾病易感性筛选试验，建议对IDDM患者未受影响的亲属以及一般人群进行“前驱糖尿病”调查是合理的。我们检测IDDM 1易感性能力的主要进展集中在识别β细胞自身免疫的血清学标记物：细胞质胰岛细胞自身抗体。最近，研究人员也开始考虑旨在中断或防止自身免疫β细胞破坏的治疗方式。一般来说，筛选试验应该是可靠的、可重复的、廉价的和无创的。ICA检测在多大程度上符合这些标准？用间接免疫荧光法在人胰腺的非固定“快速冷冻”冰冻切片上检测ICAs。非人类胰腺底物的使用，胰腺标本敏感性的差异，观察者解释的可变性，以及ICA分析方法的修改只是不同实验室报告的ICA频率不同的一些原因。例如，在新诊断的IDDM患者中，报告的ICA频率在65%至90%之间；在IDDM患者的非糖尿病一级亲属中，ICA频率在0.9%至9%之间变化。因此，对ICA检测进行标准化是公认的必要和持续的努力：1987年10月25日和26日在纽约市举行的最新ICA研讨会达成共识，建议只使用人体组织作为底物，严格遵守“盲法”解释，并在青少年糖尿病基金会单位使用基于国际定义的标准血清的标准曲线报告结果。仅在过去几年中，ICAs才被评估为β细胞功能障碍或即将发生IDDM的可能的前瞻性标志物：，6 Joslin诊所的回顾性研究表明，在IDDM患者的非糖尿病亲属中，ICAs强烈预测胰岛素缺乏（静脉注射葡萄糖后）和IDDM的最终发展。这些研究人员能够通过确定胰岛素自身抗体来提高他们识别“有风险”个体的能力。这似乎是谨慎的，因为10%至35%的IDDM患者在诊断时明显缺乏ICAs。其他潜在的疾病易感性或疾病活动性标志物包括活化的t淋巴细胞和胰岛细胞表面或蛋白免疫沉淀（Mr= 64千道尔）自身抗体：我们已经表明，在ica阳性的非糖尿病个体中，胰岛素自身抗体的存在强烈地预测了静脉注射葡萄糖的胰岛素反应较差8，并且ica阳性的非糖尿病个体在其b淋巴细胞表面有增加的HLA-DR密度。在最近一期的《华尔街日报》上，Chase等人调查了一个高风险人群的ICAs存在情况。一级亲属进行连续静脉葡萄糖耐量试验。Chase等人得出结论，一期胰岛素反应低于25 tdU/mL可预测IDDM的发展。乔斯林诊所小组先前在胰岛素反应低于对照人群的第一百分位数的基础上得出了类似的结论。从预防疾病的角度来看，必须认识到许多……
Preventive medicine is built on an appreciation of disease etiopathogenesis and natural history. Screening for disease susceptibility to insulin-dependent diabetes mellitus could allow recognition of individuals" at risk" before the development of appreciable degrees of beta cell damage. A recommendation to survey unaffected relatives of patients with IDDM, as well as the general population, for" prediabetes" would be justifiable assuming the availability of effective and safe preventive therapy and of appropriate screening tests for disease susceptibility. Major advances in our ability to detect susceptibility to IDDM 1 have centered around the recognition of a serologic marker for beta cell autoimmunity: cytoplasmic islet cell autoantibodies. 2 Recently, researchers have also begun to consider therapeutic modalities aimed at interrupting or preventing autoimmune beta cell destruction. 3 In general, screening tests should be reliable, reproducible, inexpensive, and noninvasive. How well does the ICA assay meet these criteria? ICAs are detected by indirect immunofluorescence on unfixed" snap frozen" cryosections of human pancreas. The use of nonhuman pancreatic substrate, the differences in sensitivity of the pancreatic specimens, the variability in observer interpretation, and the methodologic modifications in the ICA assay are just some of the reasons that reported ICA frequencies vary among different laboratories. For example, in newly diagnosed IDDM patients, reported ICA frequencies range between 65% and 90%; in nondiabetic first-degree relatives of IDDM patients, ICA frequencies vary between 0.9% and 9%. Thus there is a recognized necessity and an ongoing effort to standardize the ICA assay: The consensus of the latest ICA workshop held in New York City, Oct. 25 and 26, 1987, was to recommend the exclusive use of human tissue as substrate, strict adherence to" blinded" interpretation, and the reporting of results in Juvenile Diabetes Foundation units by using a standard curve based on internationally defined standard sera. Only in the past few years have ICAs been evaluated as a possible prospective marker of beta cell dysfunction or impending IDDM:, 6 The retrospective studies from the Joslin Clinic demonstrated that in nondiabetic relatives ofIDDM patients, ICAs were strongly predictive of insulinopenia (after intravenous injection of glucose) and of the eventual development of IDDM. These researchers were able to improve their ability to identify individuals" at risk" by ascertaining insulin autoantibodies. This seems prudent because 10% to 35% of IDDM patients apparently lack ICAs at the time of diagnosis. Other potential disease-susceptibility or disease-activity markers include activated T-lymphocytes and islet cell surface or proteinimmunoprecipitating (Mr= 64 kilodaltons) autoantibodies: We have shown that the presence of insulin autoantibodies in ICA-positive nondiabetic individuals strongly predicts a poor insulin response to intravenously administered glucose 8 and that ICA-positive nondiabetic individuals have an increased density of HLA-DR on the surface of their B-lymphocytes. 9 In a recent issue of The Journal, Chase et al. 1~ surveyed a high-risk population for the presence of ICAs. Firstdegree relatives with ICAs underwent serial intravenous glucose tolerance testing. Chase et al. concluded that first-phase insulin responses of less than 25 tdU/mL predict the development of IDDM. The Joslin Clinic group had previously reached a similar conclusion on the basis of an insulin response at less than the first percentile of their control population. From the viewpoint of disease prevention, it must be recognized that many of the …