P. J. Bingley . E. A. M. Gale . The European Nicotinamide Diabetes Intervention Trial (ENDIT) Group Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk

作者：P. J. Bingley, Elaine Gale · 年份：2006 · 被引用次数：18 · 研究领域：Diabetes and associated disorders、Pancreatic function and diabetes、Diabetes Management and Research

Aims/hypothesis: To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)- positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabe- tes Intervention Trial. Methods: Five hundred and forty- nine first-degree relatives with confirmed ICA levels ≥20 Juvenile Diabetes Foundation units (mean age 15.9 years; interquartile range 10.4-33.7 years) were recruited from 20 countries. OGTTs and IVGTTs were performed at baseline, antibodies to glutamate decarboxylase (GADA), protein tyrosine phosphatase (IA-2A) and insulin (IAA) were determined by RIA, and HLA class II genotyping was performed by PCR of sequence-specific oligonucleo- tides. Results: One hundred and fifty-nine participants developed diabetes within 5 years. Univariate analysis showed that the cumulative risk of development of diabetes within 5 years varied according to age, relation- ship to the proband, positivity for IAA, IA-2A and GADA, number and combination of islet antibodies, HLA class II genotype, baseline glucose tolerance, and first- phase insulin secretion, but not gender or incidence of childhood type 1 diabetes in the background population. Children aged ≤10 years had a 59% risk of diabetes within 5 years, compared with 11% in those ≥25 years (p<0.0001). Using multivariate analysis, independent determinants were age, first-phase insulin response, base- line glucose tolerance and ...