Growth differences between North American and European children at risk for type 1 diabetes

AIM: To evaluate the relationships between early growth and regional variations in type 1 diabetes (T1D) incidence in an international cohort of children with familial and genetic risk for T1D. METHODS: Anthropometric indices between birth to 5 yr of age were compared among regions and T1D proband in 2160 children participating in the Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk study. RESULTS: Children in Northern Europe had the highest weight z-score between birth to 12 months of age, while those in Southern Europe and U.S.A. had the lowest weight and length/height z-scores at most time points (p < 0.005 to p < 0.001). Few differences in z-score values for weight, height, and body mass index were found by maternal T1D status. Using International Obesity Task Force criteria, the obesity rates generally increased with age and at 5 yr were highest in males in Northern Europe (6.0%) and in females in Canada (12.8%). However, no statistically significance difference was found by geographic region. In Canada, the obesity rate for female children of mothers with and without T1D differed significantly at 4 and 5 yr (6.0 vs. 0.0% and 21.3 vs. 1.9%, respectively; p < 0.0125) but no differences by maternal T1D status were found in other regions. CONCLUSIONS: There are regional differences in early childhood growth that are consistent with the higher incidence of T1D in Northern Europe and Canada as compared to Southern Europe. Our prospective study from birth will allow evaluation of relationships between growth and the emerging development of autoimmunity and progression to T1D by region in this at-risk population of childre

Growth Differences Between North American and European Children at Risk for Type 1 Diabetes

Aim: To evaluate the relationships between early growth and regional variations in type 1 diabetes (T1D) incidence in an international cohort of children with familial and genetic risk for T1D. Methods: Anthropometric indices between birth to 5 yr of age were compared among regions and T1D proband in 2160 children participating in the Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk study. Results: Children in Northern Europe had the highest weight z-score between birth to 12 months of age, while those in Southern Europe and USA had the lowest weight and length/height z-scores at most time points (p \u3c 0.005 to p \u3c 0.001). Few differences in z-score values for weight, height, and body mass index were found by maternal T1D status. Using International Obesity Task Force criteria, the obesity rates generally increased with age and at 5 yr were highest in males in Northern Europe (6.0%) and in females in Canada (12.8%). However, no statistically significance difference was found by geographic region. In Canada, the obesity rate for female children of mothers with and without T1D differed significantly at 4 and 5 yr (6.0 vs. 0.0% and 21.3 vs. 1.9%, respectively; p \u3c 0.0125) but no differences by maternal T1D status were found in other regions. Conclusions: There are regional differences in early childhood growth that are consistent with the higher incidence of T1D in Northern Europe and Canada as compared to Southern Europe. Our prospective study from birth will allow evaluation of relationships between growth and the emerging development of autoimmunity and progression to T1D by region in this at-risk population of children

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial

Importance: Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. Objective: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. Design, Setting, and Participants: An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. Interventions: The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. Main Outcomes and Measures: Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). Results: Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). Conclusions and Relevance: Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes