ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this study, 10 145 children of 1–8 years of age, selected from a prospective systematic cohort study and stratified according to HLA-risk categories for type-1-diabetes (T1D), underwent a combined evaluation of pancreatic autoimmunity, glucose metabolism and anthropometry at different timeframes. Diagnosis of T1D occurred in 131/10,145 children (1.3%). Faster height growth, both before and after age 3 years, was significantly associated with the appearance of islet autoimmunity and the progression to T1D among subjects who seroconverted. The inclusion of growth dynamics in the risk score models may improve the accuracy of predicting time to islet autoimmunity and overt disease.

Growth is mainly driven by different factors according to a distinct time period, in particular nutrition is the main driver during infancy, growth hormone in childhood, and sex hormones in adolescence (1). Since each factor could contribute differently to the onset of T1D, the peculiar approach of this study was to focus only to the childhood period and to explore the association between the growth rate and the risk of type-1-diabetes-autoimmunity in children at high genetic risk for T1D.

Longitudinal data were collected in 10,145 children from 1 to 8 years of age, enrolled in a prospective cohort study, the ‘Type 1 Diabetes Intelligence study (T1DI) cohort’, from Finland (61.3%), Sweden (12.2%), Germany (13.1%), and the United States (13.5%), with an average follow-up period of 6.94 years (2). The study evaluated the association between 4 main predictors (height, weight, and rates of change in height and weight) and 2 main outcomes (seroconversion and T1D-onset) in 3 analysis timeframes (from 1 year of age to seroconversion; from one year of age to the onset of T1D; and from seroconversion to T1D), stratifying children into 4 different HLA-risk categories. Rapid increase in height was associated with increased risk of seroconversion to autoantibodies (hazard ratio [HR] =1.26 for 1–3 years of age and HR =1.48 for >3 years of age) and positively associated with the development of T1D (HR =1.80).

These results provide the basis to investigate the role of GH-IGF-1 axis in the onset of T1D during childhood.

References: 1. Liu X, Vehik K, Huang Y, et al; the TEDDY Study Group. Distinct growth phases in early life associated with the risk of type 1 diabetes: the TEDDY study. Diabetes Care. 2020;43(3):556–562. 2. Anand V, Li Y, Liu B, et al; T1DI Study Group. Islet autoimmunity and HLA markers of presymptomatic and Clinical Type 1 Diabetes: joint analyses of prospective cohort studies in Finland, Germany, Sweden, and the U.S. Diabetes Care. 2021;44(10):2269–2276. 3. Erlich H, Valdes AM, Noble J, et al, for the Type 1 Diabetes Genetics Consortium. HLA DR-DQ Haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008;57(4):1084–1092.