Genetic correlates of early accelerated infant growth associated with juvenile-onset type 1 diabetes

We previously showed that accelerated growth predisposing to development of childhood-onset type 1 diabetes (T1D) is restricted to the first year after birth. We assessed whether this phenomenon of increased early growth is associated with variants of two genes, insulin-like growth factor-1 (IGF1) and insulin variable number of tandem repeats (INS-VNTR), whose products are components of the growth axis.

Patients and their siblings were genotyped for the INS-VNTR and for an IGF1 microsatellite. We tested for difference in first year growth, i.e., increased weight standard deviation score (SDS), a reliable measure of especially first year growth, between carriers and non-carriers of these gene variants, using a repeated measurement and regression analysis.

In patients, growth did not differ between carriers and non-carriers of the INS-VNTR*III allele, while carriership of this allele in siblings was positively associated with increased first year growth. In both patients and siblings, non-carriership of the IGF1*194 allele was positively associated with growth. Birth size was not associated with either variant.

Non-carriership of the IGF1*194 allele was positively associated with accelerated first year growth in both patients and siblings, independent of disease. This IGF1 variant may therefore contribute to increased first year growth, but cannot explain the association of first year growth with diabetes. An effect on growth of the INS-VNTR was detected in healthy siblings, but not in patients, suggesting that disease supersedes a growth effect of INS-VNTR.