medwireNews: We dedicate this report to Professor David Dunger who very sadly died on 20th July 2021.
The human leukocyte antigen (HLA) polymorphisms that increase the risk of type 1 diabetes are linked to growth and insulin-like growth factor (IGF)-I levels during infancy, say researchers.
“Our results raise the question of whether the relationship observed between infancy weight measures or weight gains and development of islet autoimmunity in cohorts of at-risk children reflects gains in adipose tissue and is dependent on HLA genotypes”, they write in Diabetes Care.
David Dunger (University of Cambridge, UK) and colleagues draw their conclusions from data for 586 children (315 boys and 271 girls) who were monitored from birth to 24 months of age in the Cambridge Baby Growth Study.
The team found no associations between HLA risk alleles (assessed via identifying single nucleotide polymorphisms) and measures of growth at birth and between birth and 3 months of age, which they note is contrary to the hypothesis that HLA risk alleles exert their effect by influencing birthweight.
However, the DR3 risk allele was significantly associated with infant length over the full 24 months, with the effect of having two minor alleles increasing over this time, and the effect being significantly stronger in boys than girls.
The researchers note that this is in line with observational data showing “that height gains between probands developing type 1 diabetes and control subjects were more marked for boys than girls.”
The DR3-associated increase in length was accompanied by “pronounced increases” in IGF-I and IGF binding protein 3, they add. They suggest this “might be explained by the timing of [growth hormone] receptor expression that occurs after 6 months of age.”
The DQ8 risk allele was also associated with IGF-I levels at 12 and 24 months, but in the opposite direction, with lower levels found in infants with two minor alleles.
Dunger and team say this is in line with “recent reports that IGF-I levels decrease longitudinally with autoantibody positivity and are lower in carriers of high-risk HLA genotypes in infancy”.
In addition, DR4 and DQ8 were both associated with significantly greater skinfold thickness at 24 months.
“These findings could suggest distinct mechanisms involving endocrine pathways related to the HLA-conferred type 1 diabetes risk”, the researchers summarise.
By Eleanor McDermid
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