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

Abstract

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.

• Authors: Anita M Nucci, Suvi M Virtanen, David Cuthbertson, Johnny Ludvigsson, Ulle Einberg, Celine Huot, Luis Castano, Bärbel Aschemeier, Dorothy J Becker, Mikael Knip, Jeffrey P Krischer, TRIGR Investigators
• Journal: Diabetologia (Diabetologia) Vol. 64 Issue 4 Pg. 826-835 (04 2021) ISSN: 1432-0428 [Electronic] Germany
• PMID: 33474583 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Adolescent Development
• Age Factors
• Australia (epidemiology)
• Autoimmunity (genetics)
• Bottle Feeding
• Child
• Child Development
• Child, Preschool
• Diabetes Mellitus, Type 1 (epidemiology, genetics, immunology, prevention & control)
• Europe (epidemiology)
• Female
• Genetic Predisposition to Disease
• Heredity
• Humans
• Incidence
• Infant
• Infant Formula
• Infant, Newborn
• Islets of Langerhans (immunology)
• Male
• North America (epidemiology)
• Pediatric Obesity (epidemiology, immunology, prevention & control)
• Pedigree
• Phenotype
• Prognosis
• Randomized Controlled Trials as Topic
• Risk Assessment
• Risk Factors