Diabetes Care, Vol 22, Issue 11 1796-1801, Copyright © 1999 by American Diabetes Association

ARTICLES

Optimized autoantibody-based risk assessment in family members. Implications for future intervention trials

PJ Bingley, AJ Williams and EA Gale
Division of Medicine, University of Bristol, U.K. polly.bingley@bristol.ac.uk

OBJECTIVE: To determine the best autoantibody-based testing strategy for recruiting relatives for future intervention trials and to establish the role of islet cell antibodies (ICAs) within this strategy. RESEARCH DESIGN AND METHODS: ICAs, insulin autoantibodies (IAAs), GAD antibodies, and IA-2 antibodies were determined in serum samples at study entry of 3,655 non-diabetic first-degree relatives of patients with type 1 diabetes who were followed for a median of 5.5 years. The cumulative risk of diabetes associated with single and combined antibody marker levels of > or = 97.5th percentile in schoolchildren was calculated by using life-table analysis. RESULTS: Of the 26 relatives who developed insulin-requiring diabetes during follow-up, 16 were aged < 20 years and 7 were aged 20-39 years at study entry. Of the 23 cases aged < 40 years, 83% had IA-2 and/or GAD antibodies, and 87% had IAA and/or GAD antibodies > or = 97.5th percentile compared with 61% who had ICAs of > or = 5 Juvenile Diabetes Foundation units (JDF U). A two-step strategy with parallel testing for IA-2/GAD antibodies followed by IAA testing identified 50% of cases aged < 20 years and was associated with a 71% risk within 10 years. In subjects aged 20-39 years, this strategy conferred a 51% risk, whereas using ICAs as the second test gave 86% sensitivity and a 74% risk. Primary screening for IA-2 and/or GAD antibodies followed by testing for IAA and/or ICA antibodies achieved the highest sensitivity in both age-groups and conferred a 63% risk. In contrast, ICAs of > or = 20 JDF U (the inclusion criteria for the European Nicotinamide Diabetes Intervention Trial) gave 48% sensitivity and 35% risk. CONCLUSIONS: ICA testing can be replaced as a primary screening measure by IA-2/GAD or IAA/GAD antibody testing. The sensitivity of ICAs (used alone or in combination with IAAs) gives them a useful role in second-line testing. Combination testing could reduce the size of screening populations needed for recruitment in future intervention trials by approximately 50% compared with testing based on ICAs alone.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. M. Gillespie Type 1 diabetes: pathogenesis and prevention. Can. Med. Assoc. J., July 18, 2006; 175(2): 165 - 170. [Abstract] [Full Text] [PDF]

				P. Achenbach, E. Bonifacio, K. Koczwara, and A.-G. Ziegler Natural History of Type 1 Diabetes Diabetes, December 1, 2005; 54(suppl_2): S25 - S31. [Abstract] [Full Text] [PDF]

				L. C. Harrison, M. C. Honeyman, C. E. Steele, N. L. Stone, E. Sarugeri, E. Bonifacio, J. J. Couper, and P. G. Colman Pancreatic {beta}-Cell Function and Immune Responses to Insulin After Administration of Intranasal Insulin to Humans At Risk for Type 1 Diabetes Diabetes Care, October 1, 2004; 27(10): 2348 - 2355. [Abstract] [Full Text] [PDF]

				J. P. Krischer, D. D. Cuthbertson, L. Yu, T. Orban, N. Maclaren, R. Jackson, W. E. Winter, D. A. Schatz, J. P. Palmer, and G. S. Eisenbarth Screening Strategies for the Identification of Multiple Antibody-Positive Relatives of Individuals with Type 1 Diabetes J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 103 - 108. [Abstract] [Full Text] [PDF]

				K. M. Gillespie, E. A.M. Gale, and P. J. Bingley High Familial Risk and Genetic Susceptibility in Early Onset Childhood Diabetes Diabetes, January 1, 2002; 51(1): 210 - 214. [Abstract] [Full Text] [PDF]

				E. A M Gale, P. J Bingley, G. S Eisenbarth, M. J Redondo, K. O Kyvik, and J. S Petersen Reanalysis of twin studies suggests that diabetes is mainly genetic BMJ, October 27, 2001; 323(7319): 997 - 997. [Full Text]

				A. J. K. Williams, A. J. Norcross, R. J. Lock, D. J. Unsworth, E. A. M. Gale, and P. J. Bingley The High Prevalence of Autoantibodies to Tissue Transglutaminase in First-Degree Relatives of Patients With Type 1 Diabetes Is Not Associated With Islet Autoimmunity Diabetes Care, March 1, 2001; 24(3): 504 - 509. [Abstract] [Full Text]