Insulin, nutrition, insulin-like growth factors and the retina

I’d really like to see a good quality review article with that title, there are several that touch on these issues (for example, here and here), but I find the data hard to digest, probably because it is relatively novel for me.

So here is my attempt to summarize things for myself:

Recent data show that infants with poor postnatal growth have an increased risk of retinopathy (RoP), and that this seems to be  statistically be related to lower IGF levels.

Prediction models have been produced, based on neonatal growth, the main aim of which seems to be reducing and/or targeting retinal screening exams. They appear to be fairly good predictors of who will not develop RoP. If you grow well you are relatively protected from developing severe RoP.

Insulin-like Growth Factor 1 plays a rôle in retinal vascular development, it seems to be required for VEGF to have an effect. IGF1 decreases after preterm birth,  and then slowly increases. The low initial IGF1 concentration is thought to participate in poorer retinal development initially, but then, later on when the IGF1 levels increase, it permits VEGF to act, promoting neo-vascular proliferation.

IGF1 levels are also affected by/correlated with  postnatal growth, and by nutritional intakes.

IGF1 levels seem to be lower in infants who are hyperglycemic, treatment with insulin may lead to a later increase in IGF1. Optimizing nutritional intakes, improves growth, probably increases IGF1 levels and might decrease RoP. However, many of the observational and interventional studies of differing nutritional intakes have not mentioned RoP as an outcome, probably, like me, few people thought there would be a change in RoP by changing early calorie administration. Even fairly recent review articles of nutritional intakes of the preterm infant do not address retinopathy reduction as a potential benefit of improved nutrition.

I recently heard that there is a planned RCT of recombinant IGF to try and prevent retinopathy, which seems to me to be far too early given the current state of knowledge. Surely the first step should be to find ways to optimize postnatal nutrition, to have uniform optimal nutritional protocols with good quality protein and appropriate lipids. An RCT of IGF against such a background might then be worthwhile. But while postnatal growth is so poor in many very preterm babies, because their nutritional intakes do not follow guidelines, and the other benefits of optimal nutrition are numerous, I think we should have better studies showing the effects of optimal nutritional management before leaping into supplying IGF1, which might just be a way to counter our deficiencies of nutritional management!

These issues will become more important in the near future, as we increase oxygen saturation targets we need to find the best ways we can to protect the retinae of our extreme preterm babies.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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