220名糖尿病患者青少年一级亲属的一期胰岛素分泌与年龄、人类白细胞抗原、胰岛细胞抗体状态及1型糖尿病发生之间的关系

Relationship between first-phase insulin secretion and age, HLA, islet cell antibody status, and development of type I diabetes in 220 juvenile first-degree relatives of diabetic patients.

作者信息

Robert J J, Deschamps I, Chevenne D, Roger M, Mogenet A, Boitard C

机构信息

Pediatric Endocrinology and Diabetes Unit, Hospital for Sick Children, Paris, France.

出版信息

Diabetes Care. 1991 Aug;14(8):718-23. doi: 10.2337/diacare.14.8.718.

DOI:10.2337/diacare.14.8.718

PMID:1954807

Abstract

OBJECTIVE

To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes.

RESEARCH DESIGN AND METHODS

Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3-29 yr) of diabetic patients; 75 underwent two or more tests.

RESULTS

At the first test, insulin responses correlated with age in ICA- children less than or equal to 11 yr old (r = 0.46, p less than 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children less than 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA- subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA- subjects displayed distinct changes; the mean +/- SE insulin response increased in ICA- subjects from 619.2 +/- 40.8 to 716.4 +/- 50.4 pM (P less than 0.001) but declined in ICA+ subjects from 403.2 +/- 91.8 to 313.8 +/- 67.2 pM (P less than 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA- subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response.

CONCLUSIONS

Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.

摘要

目的

评估早期胰岛素反应对于预测胰岛素依赖型糖尿病发展的充分性。

研究设计与方法

测定对葡萄糖（静脉注射0.5 g/kg）的1分钟和3分钟胰岛素反应、胰岛细胞抗体（ICA）、胰岛素自身抗体（IAA）以及人类白细胞抗原（HLA）。我们研究了220名糖尿病患者的一级亲属（年龄3 - 29岁）；75人接受了两次或更多次检测。

结果

在首次检测时，年龄小于或等于11岁的ICA阴性儿童中，胰岛素反应与年龄相关（r = 0.46，p < 0.001）。所有年龄段个体反应差异很大，低值很常见（第5百分位数：5岁以下儿童为108 pM，之后为180 pM）。未发现胰岛素反应与IAA或HLA之间存在相关性。排除年龄影响后，15名ICA阳性受试者的反应与ICA阴性受试者的反应无显著差异。在后续检测中，ICA阳性和ICA阴性受试者表现出不同变化；ICA阴性受试者的平均±标准误胰岛素反应从619.2±40.8 pM增加到716.4±50.4 pM（P < 0.001），而ICA阳性受试者从403.2±91.8 pM下降到313.8±67.2 pM（P < 0.02）。在随访期间，9名持续ICA阳性的同胞中有5名（56%）患糖尿病或糖耐量受损，而54名持续ICA阴性的受试者中有1名（2%）患病。两次或更多次低胰岛素反应（<300 pM）预测糖尿病进展的敏感性和特异性分别为60%和96%；预测值为43%。持续ICA阳性、持续低胰岛素反应和HLA - DR3/4联合预测价值最高（75%）。然而，没有受试者能从胰岛素反应下降推断出糖尿病发病时间。