Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk.

AIMS/HYPOTHESIS: We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes. METHODS: Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10-14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05. RESULTS: In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2-10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling. CONCLUSIONS/INTERPRETATION: In children at genetic risk of type 1 diabetes, being overweight at 2-10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00179777.

Increasing incidence of childhood-onset type 1 diabetes mellitus among Estonian children in 1999-2006. Time trend analysis 1983-2006.

BACKGROUND: The incidence of childhood-onset type 1 diabetes mellitus (T1DM) among Estonian children under 15 years of age was 10.1 per 100,000 per year in 1983-1990 and 12.2 per 100,000 per year in 1991-1998 with the highest incidence in age-group 10.0-14.9 years in both periods. From 1983 to 1998, the incidence increased most rapidly in age-group 0-4.9 years. OBJECTIVE: To determine the incidence of T1DM among Estonian children in 1999-2006 and to compare the results with the data from 1983 to 1998. SUBJECTS AND METHODS: In 1999-2006, population-based incidence data were collected from two centers where all children with T1DM are seen after the diagnosis. Data for earlier periods were obtained from previously published data. Subjects were divided into three age-groups: 0-4.9 years, 5.0-9.9 years and 10.0-14.9 years. RESULTS: Between 1999 and 2006, 310 new cases of T1DM were diagnosed in Estonian children aged 0-14.9 years. The age-standardized incidence rate for that period was 17.2 [95% confidence interval (CI) 13.1-21.2]. The incidence was the highest, 21.2 (95% CI 17.7-25.3) in age-group 5.0-9.9 years. Over the time period 1983-2006, the incidence of childhood-onset T1DM in Estonian children under 15 years of age increased annually by an average 3.3% with the most rapid annual increase-9.3%-occurring in the youngest age-group. CONCLUSIONS: The incidence of childhood-onset T1DM in Estonia continues to rise and the age of onset of the disease becomes younger.