Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes

Abstract

Aims/hypothesis The aim of this work was to examine the relationship between family history of type 1 diabetes, birthweight, growth during the first 2 years and development of multiple beta cell autoantibodies in children with a first-degree relative with type 1 diabetes and HLA-conferred disease susceptibility. Methods In a secondary analysis of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), clinical characteristics and development of beta cell autoantibodies were compared in relation to family history of type 1 diabetes (mother vs father vs sibling) in 2074 children from families with a single affected family member. Results Multiple autoantibodies (≥2 of 5 measured) developed in 277 (13%) children: 107 (10%), 114 (16%) and 56 (18%) born with a mother, father or sibling with type 1 diabetes, respectively (p < 0.001). The HR for time to multiple autoimmunity was 0.54 (95% CI 0.39, 0.75) in offspring of affected mothers (n = 107/1046, p < 0.001) and 0.81 (95% CI 0.59, 1.11) (n = 114/722, p = 0.19) in offspring of affected fathers, compared with participants with a sibling with type 1 diabetes (comparator group n = 56/306). The time to the first autoantibody present (to insulin, GAD, tyrosine phosphatase-related insulinoma-associated 2 molecules, islet cell or zinc transporter 8) was similar in the three groups. Height velocity (z score/year) in the first 24 months was independently associated with developing multiple antibodies in the total cohort (HR 1.31 [95% CI 1.01, 1.70], p = 0.04). A higher birthweight in children born to an affected mother vs affected father or an affected sibling was not related to the risk of multiple autoimmunity. Conclusions/interpretation The risk of developing multiple autoantibodies was lower in children with maternal type 1 diabetes. For the whole group, this risk of developing multiple autoantibodies was independent of birthweight but was greater in those with increased height velocity during the first 2 years of life. However, the risk associated with paternal type 1 diabetes was not linked to differences in birthweight or early growth. Trial registration ClinicalTrials.gov NCT00179777 Graphical abstract

Growth in Children with HLA-Conferred Susceptibility to Type 1 Diabetes

“…Our results are different from the TEDDY study, where children with increased genetic risk for T1D were leaner than the general population [14]. However, increased height and weight gain in childhood have been found to be associated with the development of islet autoimmunity or T1D, supporting the accelerator hypothesis [2,18,19]. Children who developed diabetes before 6 years of age were significantly taller from 6 to 18 months of age when corrected for MPH [3].…”

Childhood Height Growth Rate Association With the Risk of Islet Autoimmunity and Development of Type 1 Diabetes

“…It is also in agreement with our finding of negative association of height and development of islet autoimmunity by age 8 years. In the TRIGR study, the risk of islet autoimmunity with multiple autoantibodies was positively associated with the child’s height velocity during the first 2 years of life ( 24 ). In the DAISY study, greater height growth velocity of children over 2 years of age was associated with both increased risk of islet autoimmunity and type 1 diabetes ( 2 ).…”

The Causes of Insulin Resistance in Type 1 Diabetes Mellitus: Is There a Place for Quaternary Prevention?

“…Pacaud et al, in a secondary analysis of the TRIGR study, compared the clinical characteristics and development of β-cell autoantibodies in patients with a family history of T1DM. The research involved 2074 children from families with a single family member (mother, father, or sibling) affected by T1DM [ 54 ]. The study showed that the risk to develop β-cell autoimmunity was significantly lower ( p < 0.001) in children with maternal T1DM than with other family members with T1DM.…”