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Catch me if you can

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Before my foray into the world of celebrities I was talking about babies, children and the effect that illness can have on their metabolism. I have also alluded to something called catch up growth and the fact that it might be important for the overall risk of obesity and chronic disease.

What is catch up growth? The medical dictionary defines it as:

“…an acceleration of the growth rate following a period of growth retardation caused by a secondary deficiency, such as acute malnutrition or severe illness…”

The easiest way to track catch up growth in visual form (and you know that I like my visuals) is on growth charts. Children tend to follow an individual growth curve, predetermined largely by genetics, and this phenomenon is called “the canalisation of growth”. As we have established in the previous post, an illness or or a period of malnutrition may result in falling off the curve. Catch up growth is the body’s attempt to get back onto the original curve.

Growth curve flattening and fall (example only)

Accelerated growth during recovery phase

It has been known for quite a long time from observational studies that babies and children who undergo a period of catch up growth seem to be at higher risk for obesity and diabetes later in life. This was also observed in children born small for gestational age (SGA),  which is an indirect indicator of fetal malnutrition. Similar phenomenon was noted in children growing up in famines (the Dutch famine study) and the survivors of the Leningrad blockade in the WW2.

Studies conducted in the 60’s and 70’s looked further into the energy metabolism of catch up growth. They showed that the rate of growth in these children is astonishingly up to 15-20 times the rate of normal pattern. Moreover, this period was accompanied by both increase in appetite and increase in BMR in the order of 4-5 times the controls. It seems that when children were fed ad libitum they spontaneously increased their food intake to ensure their bodies get back on the curve. As their weight approached the expected measure for height their appetite would decrease back to normal levels.

Another interesting observation made around 1980 was that children do not regain lean body mass at the same rate as they lose it. Muscle recovery lags behind the recovery of fat tissue even when children regain their weight and get back on their growth curve. As one of the studies frames it:

“The impressive gains in weight made by recovering malnourished infants are largely fat; reconstitution of lean tissue does not occur equally well at all rates of weight gain.”

Let’s go back to some visuals or rather my illustration of the above.

Body composition changes during illness and recovery

The greater degree of the initial weight loss, the more unbalanced the pattern of catch up growth.

Later research started to elucidate the mechanism by how this imbalance occurs. Several studies have identified that the phenomenon of catch up fat is accompanied by hyperinsulinaemia, relative insulin resistance in skeletal muscles and hyperresponsiveness to insulin in adipose tissue.

Basically, when the child is recovering from a period of malnutrition their bodies produce more insulin for the same amount of glucose. Their muscles “shut down” the insulin gates and their fat tissue opens the gates wide so that glucose is shuttled away from the muscles and into fat.

Some of the more recent studies have tried to explain this phenomenon using terms like “thrifty gene”. Since no such gene has yet been identified to my knowledge I’m a little unconvinced. What interests me however is whether this slightly worrying pattern is diet-dependent. In other words, what do you feed a sick malnourished child to prevent this from happening? Is there a single dietary cause? What did all these children in observational studies eat?

Looking for causes in cohort data is always a fruitless exercise and a reminder that we should use it to generate hypotheses only. Randomised controlled studies on actual babies are obviously out of the question, I doubt there is an ethics committee on earth which would agree to withholding food from children and then watch them lose and then regain weight on various dietary regimens. There are always rats but they have an obvious disadvantage of being…well, rats.

One zealous study examined the rats undergoing catch up growth after semi-starvation. Those re-fed a high-fat diet were found to have more hypinsulinaemia, higher fat deposition and lower metabolic rate than the rats fed a low-fat diet. Both re-fed groups had worse metabolic derangement compared to controls. A closer attention to the high-fat diet tells you that the rats were fed 1:1 corn oil:lard mixture as 50% of their diet. What does it tell you? That it’s not a good idea to feed rats 25% of their diet as corn oil. Not much else really. It also makes it clear that both re-feeding diets resulted in higher insulin response to the same glucose load, higher adiposity, lower thermogenesis and other markers of disordered metabolism.

So we are back to generating hypotheses.

Recent developments implicate a group of messengers called IGFs, insulin-like growth factors. A series of experiments on none other than zebrafish showed that low cell oxygen level as would occur in malnutrition or disease can disrupt IGF signalling which activated the MAP kinase pathway, necessary for growth. Restoring oxygen to the tissues did not always result in full system reboot. Pathways other than MAP kinase may be activated which could explain the different growth pattern. Sigh… let’s wait for the zebrafish to give us the answer.

While you are digesting all of this info I will put together my take on some of these fascinating issues. Of course, I could be the only one who actually finds this stuff so intriguing and you might be going about your day without giving the concept of catch up growth a second thought. But I reckon some of this might still apply to you whether you are a determined bachelor or a mother of four. What if you were the one who had a prolonged illness at some point in your childhood? What if this pattern of metabolic disregulation also applies to the yo-yo dieters amongst us? Aha, now you are thinking about this.

Look out for my summary post on child metabolism in the next couple of days.

More reading:

Ashworth A, Milward DJ, Catch up growth in children (1986) Nutrition Reviews 44(5):157-163

Jackson AA, Wootton SA, The energy requirement of growth and catch up growth, Proceedings of an I/D/E/C/G Workshop held in Cambridge, USA 1989

Dulloo AG et al, Pathways from weight fluctuations to metabolic diseases: focus on maladaptive thermogenesis during catch-up fat (2002) International Journal of Obesity 26(S2): S46-S57

Ong KKL et al, Association between postnatal catch-up growth and obesity in childhood: prospective cohort study (2000) BMJ 320:7240

 

 



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