AIMS/HYPOTHESIS: The aim of the study was to investigate the timing of the appearance of autoantibodies associated with type 1 diabetes between birth and puberty, the natural fate of these autoantibodies and the predictive power of autoantibody concentrations for early progression to clinical diabetes. METHODS: Children were recruited to the Type 1 Diabetes Prediction and Prevention Project, an ongoing study based on HLA-conferred genetic risk. Autoantibodies against islet cells, insulin, GAD65 and islet antigen 2 were analysed at 3-12 month intervals, starting from birth. RESULTS: During the follow-up, 1,320 children (18.4% of the cohort of 7,165 children) were autoantibody positive in at least one sample. Altogether, 184 autoantibody-positive children progressed to type 1 diabetes. Seroconversion occurred at an early age in the progressors (median 1.5 years), among whom 118 (64%) and 150 (82%) seroconverted to autoantibody positivity before the age of 2 and 3 years, respectively. The incidence of seroconversion peaked at 1 year of age. Compared with other autoantibody-positive children, the median autoantibody levels were already markedly higher 3 to 6 months after the seroconversion in children who later progressed to diabetes. CONCLUSIONS/ INTERPRETATION: Early initiation of autoimmunity and rapid increases in autoantibody titres strongly predict progression to overt diabetes before puberty, emphasising the importance of early life events in the development of type 1 diabetes.
AIMS/HYPOTHESIS: The aim of the study was to investigate the timing of the appearance of autoantibodies associated with type 1 diabetes between birth and puberty, the natural fate of these autoantibodies and the predictive power of autoantibody concentrations for early progression to clinical diabetes. METHODS:Children were recruited to the Type 1 Diabetes Prediction and Prevention Project, an ongoing study based on HLA-conferred genetic risk. Autoantibodies against islet cells, insulin, GAD65 and islet antigen 2 were analysed at 3-12 month intervals, starting from birth. RESULTS: During the follow-up, 1,320 children (18.4% of the cohort of 7,165 children) were autoantibody positive in at least one sample. Altogether, 184 autoantibody-positive children progressed to type 1 diabetes. Seroconversion occurred at an early age in the progressors (median 1.5 years), among whom 118 (64%) and 150 (82%) seroconverted to autoantibody positivity before the age of 2 and 3 years, respectively. The incidence of seroconversion peaked at 1 year of age. Compared with other autoantibody-positive children, the median autoantibody levels were already markedly higher 3 to 6 months after the seroconversion in children who later progressed to diabetes. CONCLUSIONS/ INTERPRETATION: Early initiation of autoimmunity and rapid increases in autoantibody titres strongly predict progression to overt diabetes before puberty, emphasising the importance of early life events in the development of type 1 diabetes.
Authors: Kirsti Näntö-Salonen; Antti Kupila; Satu Simell; Heli Siljander; Tiina Salonsaari; Anne Hekkala; Sari Korhonen; Risto Erkkola; Jukka I Sipilä; Lotta Haavisto; Marja Siltala; Juhani Tuominen; Jari Hakalax; Heikki Hyöty; Jorma Ilonen; Riitta Veijola; Tuula Simell; Mikael Knip; Olli Simell Journal: Lancet Date: 2008-09-22 Impact factor: 79.321
Authors: Sergey Nejentsev; Joanna M M Howson; Neil M Walker; Jeffrey Szeszko; Sarah F Field; Helen E Stevens; Pamela Reynolds; Matthew Hardy; Erna King; Jennifer Masters; John Hulme; Lisa M Maier; Deborah Smyth; Rebecca Bailey; Jason D Cooper; Gloria Ribas; R Duncan Campbell; David G Clayton; John A Todd Journal: Nature Date: 2007-11-14 Impact factor: 49.962
Authors: Hanna Viskari; Sami Oikarinen; Sanna Hoppu; Tytti Vuorinen; Heini Huhtala; Jorma Toppari; Riitta Veijola; Jorma Ilonen; Mikael Knip; Heikki Hyöty Journal: Diabetologia Date: 2017-09-02 Impact factor: 10.122