Genetic support for insulin system role in growth hormone response

By Eleanor McDermid, Senior medwireNews Reporter

Genetic determinants of insulin sensitivity are positively related to spontaneous growth and response to growth hormone (GH) treatment in children born small for gestational age (SGA), researchers have found.

A genetic score based on single nucleotide polymorphisms known to affect insulin sensitivity was associated with spontaneous post-natal weight gain, and with height velocity, weight and change in insulin-like growth factor (IGF)-I levels in children receiving GH therapy, report Rikke Beck Jensen (University of Copenhagen, Denmark) and co-workers.

However, when they added the genetic insulin sensitivity score to the Ranke growth prediction model for SGA children, it accounted for only an additional 5% of the variability in GH response, increasing the variability accounted for from 17% to 22%, which the team says “is insufficient for such scores to have clinical utility in individual treatment prediction.”

But they write in The Journal of Clinical Endocrinology & Metabolism: “It will be interesting to examine whether similar mechanisms contribute to growth responses in patients with other conditions that warrant GH therapy, such as GH deficiency.”

Among the 96 SGA children studied, each additional allele in the insulin sensitivity score was associated with a 0.12 standard deviation score (SDS) increase in spontaneous weight gain between birth and entry to the North European SGA Study. And each allele increase in an insulin secretion genetic score was associated with a 0.15 SDS increase in height gain during this period. Both associations were independent of age, gender and mid-parental height.

During 1 year of GH treatment, the insulin sensitivity score was positively associated with change in height and in IGF-I levels, at 0.18 cm/year and 0.17 SDS, respectively, per allele increase. The score was associated with weight at baseline and 1 year, but not with weight change.

The team found that adding baseline IGF-I SDS, rather than the insulin sensitivity score, to the Ranke prediction model accounted for an additional 9% of the variability in response to GH, increasing that accounted for from 17% to 26%.

Commenting on the study, Martin Savage, Emeritus Professor of Paediatric Endocrinology from Barts and the London School of Medicine & Dentistry, UK, told medwireNews: “These findings are not immediately relevant to the practical management of short stature related to SGA, but they do confirm the importance of insulin secretion and sensitivity in the context of the SGA child.

“Ultimately the induction of greater insulin sensitivity may become a therapeutic goal with the aim of further improving the growth response in patients requiring GH therapy for optimal growth.”

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