Abstract
Islet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers > or = 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age-matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICA-positive schoolchildren and ICA-positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15-74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atkinson M. A., Maclaren N. K., Riley W. J., Winter W. E., Fisk D. D., Spillar R. P. Are insulin autoantibodies markers for insulin-dependent diabetes mellitus? Diabetes. 1986 Aug;35(8):894–898. doi: 10.2337/diab.35.8.894. [DOI] [PubMed] [Google Scholar]
- Atkinson M. A., Maclaren N. K., Scharp D. W., Lacy P. E., Riley W. J. 64,000 Mr autoantibodies as predictors of insulin-dependent diabetes. Lancet. 1990 Jun 9;335(8702):1357–1360. doi: 10.1016/0140-6736(90)91241-2. [DOI] [PubMed] [Google Scholar]
- Baekkeskov S., Aanstoot H. J., Christgau S., Reetz A., Solimena M., Cascalho M., Folli F., Richter-Olesen H., De Camilli P., Camilli P. D. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 1990 Sep 13;347(6289):151–156. doi: 10.1038/347151a0. [DOI] [PubMed] [Google Scholar]
- Bergua M., Solé J., Marion G., Perez M. C., Recasens A., Fernàndez J., Casamitjana R., Gomis R. Prevalence of islet cell antibodies, insulin antibodies and hyperglycaemia in 2291 schoolchildren. Diabetologia. 1987 Sep;30(9):724–726. doi: 10.1007/BF00296996. [DOI] [PubMed] [Google Scholar]
- Betterle C., Presotto F., Pedini B., Moro L., Slack R. S., Zanette F., Zanchetta R. Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value for the development of type 1 (insulin-dependent) diabetes mellitus. A 10-year follow-up study. Diabetologia. 1987 May;30(5):292–297. doi: 10.1007/BF00299020. [DOI] [PubMed] [Google Scholar]
- Bingley P. J., Bonifacio E., Gale E. A. Can we really predict IDDM? Diabetes. 1993 Feb;42(2):213–220. doi: 10.2337/diab.42.2.213. [DOI] [PubMed] [Google Scholar]
- Bonifacio E., Bingley P. J., Shattock M., Dean B. M., Dunger D., Gale E. A., Bottazzo G. F. Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes. Lancet. 1990 Jan 20;335(8682):147–149. doi: 10.1016/0140-6736(90)90013-u. [DOI] [PubMed] [Google Scholar]
- Bonifacio E., Boitard C., Gleichmann H., Shattock M. A., Molenaar J. L., Bottazzo G. F. Assessment of precision, concordance, specificity, and sensitivity of islet cell antibody measurement in 41 assays. Diabetologia. 1990 Dec;33(12):731–736. doi: 10.1007/BF00400345. [DOI] [PubMed] [Google Scholar]
- Bonifacio E., Lernmark A., Dawkins R. L. Serum exchange and use of dilutions have improved precision of measurement of islet cell antibodies. J Immunol Methods. 1988 Jan 21;106(1):83–88. doi: 10.1016/0022-1759(88)90274-8. [DOI] [PubMed] [Google Scholar]
- Bärmeier H., McCulloch D. K., Neifing J. L., Warnock G., Rajotte R. V., Palmer J. P., Lernmark A. Risk for developing type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies. Diabetologia. 1991 Oct;34(10):727–733. doi: 10.1007/BF00401518. [DOI] [PubMed] [Google Scholar]
- Dahlquist G., Gustavsson K. H., Holmgren G., Hägglöf B., Larsson Y., Nilsson K. O., Samuelsson G., Sterky G., Thalme B., Wall S. The incidence of diabetes mellitus in Swedish children 0-14 years of age. A prospective study 1977-1980. Acta Paediatr Scand. 1982 Jan;71(1):7–14. doi: 10.1111/j.1651-2227.1982.tb09364.x. [DOI] [PubMed] [Google Scholar]
- Gorsuch A. N., Spencer K. M., Lister J., McNally J. M., Dean B. M., Bottazzo G. F., Cudworth A. G. Evidence for a long prediabetic period in type I (insulin-dependent) diabetes mellitus. Lancet. 1981 Dec 19;2(8260-61):1363–1365. doi: 10.1016/s0140-6736(81)92795-1. [DOI] [PubMed] [Google Scholar]
- Greenbaum C. J., Palmer J. P., Nagataki S., Yamaguchi Y., Molenaar J. L., Van Beers W. A., MacLaren N. K., Lernmark A. Improved specificity of ICA assays in the Fourth International Immunology of Diabetes Serum Exchange Workshop. Diabetes. 1992 Dec;41(12):1570–1574. doi: 10.2337/diab.41.12.1570. [DOI] [PubMed] [Google Scholar]
- Karjalainen J. K. Islet cell antibodies as predictive markers for IDDM in children with high background incidence of disease. Diabetes. 1990 Sep;39(9):1144–1150. doi: 10.2337/diab.39.9.1144. [DOI] [PubMed] [Google Scholar]
- Krischer J. P., Schatz D., Riley W. J., Spillar R. P., Silverstein J. H., Schwartz S., Malone J., Shah S., Vadheim C. M., Rotter J. I. Insulin and islet cell autoantibodies as time-dependent covariates in the development of insulin-dependent diabetes: a prospective study in relatives. J Clin Endocrinol Metab. 1993 Sep;77(3):743–749. doi: 10.1210/jcem.77.3.8370696. [DOI] [PubMed] [Google Scholar]
- Landin-Olsson M., Palmer J. P., Lernmark A., Blom L., Sundkvist G., Nyström L., Dahlquist G. Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children. Diabetologia. 1992 Nov;35(11):1068–1073. doi: 10.1007/BF02221683. [DOI] [PubMed] [Google Scholar]
- Lévy-Marchal C., Tichet J., Fajardy I., Gu X. F., Dubois F., Czernichow P. Islet cell antibodies in normal French schoolchildren. Diabetologia. 1992 Jun;35(6):577–582. doi: 10.1007/BF00400487. [DOI] [PubMed] [Google Scholar]
- Maclaren N. K. How, when, and why to predict IDDM. Diabetes. 1988 Dec;37(12):1591–1594. doi: 10.2337/diab.37.12.1591. [DOI] [PubMed] [Google Scholar]
- Maclaren N., Schatz D., Drash A., Grave G. Initial pathogenic events in IDDM. Diabetes. 1989 Apr;38(4):534–538. doi: 10.2337/diab.38.4.534. [DOI] [PubMed] [Google Scholar]
- Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966 Mar;50(3):163–170. [PubMed] [Google Scholar]
- Notsu K., Oka N., Note S., Nabeya N., Kuno S., Sakurami T. Islet cell antibodies in the Japanese population and subjects with type 1 (insulin-dependent) diabetes. Diabetologia. 1985 Sep;28(9):660–662. doi: 10.1007/BF00291971. [DOI] [PubMed] [Google Scholar]
- Palmer J. P., Wilkin T. J., Kurtz A. B., Bonifacio E. The Third International Workshop on the Standardisation of Insulin Autoantibody Measurement. Diabetologia. 1990 Jan;33(1):60–61. doi: 10.1007/BF00586462. [DOI] [PubMed] [Google Scholar]
- Riley W. J., Maclaren N. K., Krischer J., Spillar R. P., Silverstein J. H., Schatz D. A., Schwartz S., Malone J., Shah S., Vadheim C. A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. N Engl J Med. 1990 Oct 25;323(17):1167–1172. doi: 10.1056/NEJM199010253231704. [DOI] [PubMed] [Google Scholar]
- Schatz D. A., Barrett D. J., Maclaren N. K., Riley W. J. Polyclonal nature of islet cell antibodies in insulin-dependent diabetes. Autoimmunity. 1988;1(1):45–50. doi: 10.3109/08916938808997175. [DOI] [PubMed] [Google Scholar]
- Soeldner J. S., Tuttleman M., Srikanta S., Ganda O. P., Eisenbarth G. S. Insulin-dependent diabetes mellitus and autoimmunity: islet-cell autoantibodies, insulin autoantibodies, and beta-cell failure. N Engl J Med. 1985 Oct 3;313(14):893–894. doi: 10.1056/NEJM198510033131417. [DOI] [PubMed] [Google Scholar]
- Srikanta S., Ganda O. P., Rabizadeh A., Soeldner J. S., Eisenbarth G. S. First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion. N Engl J Med. 1985 Aug 22;313(8):461–464. doi: 10.1056/NEJM198508223130801. [DOI] [PubMed] [Google Scholar]
- Tarn A. C., Thomas J. M., Dean B. M., Ingram D., Schwarz G., Bottazzo G. F., Gale E. A. Predicting insulin-dependent diabetes. Lancet. 1988 Apr 16;1(8590):845–850. doi: 10.1016/s0140-6736(88)91601-7. [DOI] [PubMed] [Google Scholar]
- Vardi P., Dib S. A., Tuttleman M., Connelly J. E., Grinbergs M., Radizabeh A., Riley W. J., Maclaren N. K., Eisenbarth G. S., Soeldner J. S. Competitive insulin autoantibody assay. Prospective evaluation of subjects at high risk for development of type I diabetes mellitus. Diabetes. 1987 Nov;36(11):1286–1291. doi: 10.2337/diab.36.11.1286. [DOI] [PubMed] [Google Scholar]