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  • Title: Identification of prediabetes in first-degree relatives at intermediate risk of type I diabetes.
    Author: Truyen I, De Grijse J, Weets I, Kaufman L, Pipeleers L, Nanos N, Decochez K, Hilbrands R, Kaufman JM, Keymeulen B, Mathieu C, Van Gaal L, Pipeleers DG, Gorus FK, Belgian Diabetes Registry.
    Journal: Clin Exp Immunol; 2007 Aug; 149(2):243-50. PubMed ID: 17521324.
    Abstract:
    Prevention trials of type I diabetes are limited by recruitment of individuals at high risk of the disease. We investigated whether demographic and biological characteristics can identify rapid progressors among first-degree relatives of known patients at intermediate (< 10%) 5-year risk. Diabetes-associated antibodies, random proinsulin : C-peptide (PI/C) ratio and HLA DQ genotype were determined (repeatedly) in 258 islet antibody-positive IA-2Antibody-negative (Abpos/IA-2Aneg) normoglycaemic first-degree relatives. During follow-up (median 81 months), 14 of 258 Abpos/IA-2Aneg relatives developed type I diabetes; 13 (93%) of them had persistent antibodies conferring a 12% [95% confidence interval (CI): 5-19%] 5-year risk of diabetes. In Abpos/IA-2Aneg relatives with persistent antibodies (n = 126), the presence of >/= 1 HLA DQ susceptibility haplotype in the absence of a protective haplotype (P = 0.033) and appearance on follow-up of a high PI/C ratio (P = 0.007) or IA-2A-positivity (P = 0.009) were identified as independent predictors of diabetes. In persistently antibody-positive relatives with HLA DQ risk a recurrently high PI/C ratio or development of IA-2A identified a subgroup (n = 32) comprising 10 of 13 (77%) prediabetic relatives and conferred a 35% (95% CI: 18-53%) 5-year risk. Under age 15 years, 5-year progression (95% CI) was 57% (30-84%) and sensitivity 62%. In the absence of IA-2A, the combination of antibody persistence, HLA DQ risk and elevated PI/C ratio or later development of IA-2A and young age defines a subgroup of relatives with a high risk of type I diabetes (>/= 35% in 5 years). Together with initially IA-2A-positive relatives these individuals qualify for standardized beta cell function tests in view of prevention trials.
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