ABSTRACT
BACKGROUND: Nicotinamide has been used with success to prevent type 1 diabetes in animal models and humans. This vitamin B3 derivative has attracting effects on beta-cell protection and regeneration. AIM/HYPOTHESIS: To evaluate the effect of standard nicotinamide administration on type 1 diabetes prevention in first degree relatives of persons with type 1 diabetes as well as on the concentrations of islet-cell-related autoantibodies, insulin secretion and peripheral sensitivity. SUBJECTS AND METHODS: A randomized double-blind placebo controlled intervention trial was conducted in 40 first degree relatives of type 1 diabetic patients. Persistence of ICA ( >or= 10 JDF units) was among inclusion criteria. Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or placebo for 5 years. Groups were also stratified by age. Islet associated antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT, IVGTT and HLA-DR genotyping were performed in all participants. The main criterion to stop treatment was type 1 diabetes development as defined by WHO. RESULTS: Type 1 diabetes development frequencies were similar between the treatment groups. ICA frequencies at the end of the study, first phase insulin release, and insulin sensitivity did not differ between groups as well. None of the participants suffered from any adverse events described for nicotinamide. CONCLUSIONS: Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.
Subject(s)
Diabetes Mellitus, Type 1/prevention & control , Niacinamide/therapeutic use , Prediabetic State/drug therapy , Vitamin B Complex/therapeutic use , Adolescent , Adult , Autoantibodies/blood , Autoantibodies/immunology , Blood Glucose/metabolism , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Double-Blind Method , Female , Genetic Predisposition to Disease , Glucose Tolerance Test , HLA-DR Antigens/blood , Humans , Insulin/blood , Insulin/metabolism , Insulin Secretion , Male , Niacinamide/analogs & derivatives , Niacinamide/urine , Prediabetic State/blood , Prediabetic State/immunologyABSTRACT
Type 1 diabetes associated genes account for less than 50% of disease susceptibility. Human enteroviruses have been implicated as environmental factors that might trigger and/or accelerate this autoimmune disorder. We now report of a 12-year-old girl that developed pancreatic autoimmunity and type 1 diabetes after enteroviral infection. Diabetes-associated autoimmunity was evaluated by measurement of several islet cell related autoantibodies. Neutralizing antibodies to different enteroviruses were determined in the case and eight children suffering from aseptic meningitis during a large scale epidemic. Several types of diabetes-associated antibodies were detected post-infection in the adolescent with newly diagnosed type 1 diabetes, including islet cell antibodies (ICA) and tyrosine phosphatase antibodies (IA2A). ICA but not IA2A appeared in the non-diabetic enterovirus-infected subjects. Based on virological studies, type 1 diabetes pathogenesis process could have been triggered by echovirus 30 infections. This study provides the first evidence of an association between echovirus 30 infection with the presence of pancreatic autoimmunity and type 1 diabetes. Our data suggest that echovirus 30 Cuban strain could be considered a potentially diabetogenic enteroviral variant.
