P J Bingley1, E A M Gale. 1. Diabetes and Metabolism, Department of Clinical Science at North Bristol, University of Bristol, Southmead Hospital, UK. polly.bingley@bristol.ac.uk
Abstract
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 Diabetes Intervention Trial. METHODS: Five hundred and forty-nine first-degree relatives with confirmed ICA levels > or =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 oligonucleotides. 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, relationship 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 < or =10 years had a 59% risk of diabetes within 5 years, compared with 11% in those > or =25 years (p<0.0001). Using multivariate analysis, independent determinants were age, first-phase insulin response, baseline glucose tolerance and number of additional antibody markers, but not antibody type or genotype. Individuals <25 years with two or more additional antibodies at baseline had a 62% risk of diabetes within 5 years and these combined criteria identified 81% of the cases in the whole cohort. CONCLUSIONS/ INTERPRETATION: We suggest that screening and recruitment for future intervention trials should be limited to family members aged <25 years, and should be based on islet autoantibodies alone.
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 NicotinamideDiabetes Intervention Trial. METHODS: Five hundred and forty-nine first-degree relatives with confirmed ICA levels > or =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 oligonucleotides. 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, relationship 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 < or =10 years had a 59% risk of diabetes within 5 years, compared with 11% in those > or =25 years (p<0.0001). Using multivariate analysis, independent determinants were age, first-phase insulin response, baseline glucose tolerance and number of additional antibody markers, but not antibody type or genotype. Individuals <25 years with two or more additional antibodies at baseline had a 62% risk of diabetes within 5 years and these combined criteria identified 81% of the cases in the whole cohort. CONCLUSIONS/ INTERPRETATION: We suggest that screening and recruitment for future intervention trials should be limited to family members aged <25 years, and should be based on islet autoantibodies alone.
Authors: J Seissler; N G Morgenthaler; P Achenbach; E F Lampeter; D Glawe; M Payton; M Christie; W A Scherbaum Journal: Diabetologia Date: 1996-11 Impact factor: 10.122
Authors: C F Verge; R Gianani; E Kawasaki; L Yu; M Pietropaolo; R A Jackson; H P Chase; G S Eisenbarth Journal: Diabetes Date: 1996-07 Impact factor: 9.461
Authors: Laura M Jacobsen; Laura Bocchino; Carmella Evans-Molina; Linda DiMeglio; Robin Goland; Darrell M Wilson; Mark A Atkinson; Tandy Aye; William E Russell; John M Wentworth; David Boulware; Susan Geyer; Jay M Sosenko Journal: Diabetologia Date: 2019-11-25 Impact factor: 10.122
Authors: P Achenbach; K Warncke; J Reiter; A J K Williams; A G Ziegler; P J Bingley; E Bonifacio Journal: Diabetologia Date: 2006-09-26 Impact factor: 10.122
Authors: J De Grijse; M Asanghanwa; B Nouthe; N Albrecher; P Goubert; I Vermeulen; S Van Der Meeren; K Decochez; I Weets; B Keymeulen; V Lampasona; J Wenzlau; J C Hutton; D Pipeleers; F K Gorus Journal: Diabetologia Date: 2009-11-29 Impact factor: 10.122
Authors: Heli T A Siljander; Satu Simell; Anne Hekkala; Jyrki Lähde; Tuula Simell; Paula Vähäsalo; Riitta Veijola; Jorma Ilonen; Olli Simell; Mikael Knip Journal: Diabetes Date: 2009-09-15 Impact factor: 9.461
Authors: Jay M Sosenko; Jerry P Palmer; Lisa Rafkin-Mervis; Jeffrey P Krischer; David Cuthbertson; Jeffery Mahon; Carla J Greenbaum; Catherine C Cowie; Jay S Skyler Journal: Diabetes Care Date: 2009-06-01 Impact factor: 19.112