Rapid childhood growth rate tied to elevated risk of islet autoimmunity, T1D development

Children who grow in height fast appears to have a higher risk of islet autoimmunity (IAA) and rapid progression to type 1 diabetes (T1D), a study has found.

“Including rapid childhood growth in risk score models may improve the prediction accuracy of time to IAA and T1D,” the researchers said.

A total of 10,145 children aged 1‒8 years from Finland, Germany, Sweden, and the US, with at least three height and weight measurements and at least one measurement of IAA, were included in this prospective cohort study. The researchers obtained and analysed longitudinal data of childhood growth and development of IAA and T1D. The appearance of IAA and progression from IAA to T1D were the primary outcomes.

Rapid increase in height during childhood was predictive of an increased risk of seroconversion to glutamic acid decarboxylase autoantibody, insulin autoantibody, or insulinoma-like antigen-2 antibody (for age 1‒3 years: hazard ratio [HR], 1.26, 95 percent confidence interval [CI], 1.05‒1.51; for age >3 years: HR, 1.48, 95 percent CI, 1.28‒1.73). [J Clin Endocrinol Metab 2022;107:1520-1528]

In analyses from seroconversion with insulin autoantibody to diabetes, height rate was also found to have positive correlation with the development of T1D (HR, 1.80, 95 percent CI, 1.15‒2.81).

“Our results are in agreement with those from the TEDDY study that showed a positive association of accelerated childhood growth with progression to diabetes,” the researchers said. “Interestingly, the same study showed an inverse association between rapid infant growth and progression to diabetes, emphasizing the importance of analysing growth rates at distinct time periods.” [Diabetes Care 2020;43:556-562]

Of note, the researchers were not able to find out whether rapid growth rate causes the increased risk of IAA and further progression to T1D. However, they explained that “rapid growth usually comes with high growth hormone and insulin-like growth factor 1 (IGF-1) levels, which may interact with insulin and glucose metabolism.”

“The roles of growth hormone and IGF-1 are not similar in infancy and childhood, as infant growth is less dependent on growth hormone than childhood growth,” they said.

On the other hand, weight rate showed an inverse association with the rate of progression to T1D. This trend could be driven by the typical weight loss prior to clinical diagnosis, according to the researchers.

“However, there was also an inverse association with weight rate and onset of islet autoimmunity, which cannot be explained by preclinical weight loss and needs further investigation,” they added.

The present study had certain limitations. First, the infant growth phase was not analysed, which limited comparability to earlier studies covering growth from birth onwards. In addition, visit schedules, as well as the inclusion criteria, varied. Despite such differences, the data were combined and harmonized to perform the needed analyses.

“Further work is needed to investigate how much improvement in the risk score can be gained, as well as to elucidate the biological mechanism that may explain these associations,” the researchers said.